A Study of the Safety and Efficacy of Pembrolizumab (MK-3... | NCT02130466 | Trialant
NCT02130466
Sponsor
Merck Sharp & Dohme LLC
Status
Completed
Last Update Posted
Aug 1, 2022Actual
Enrollment
184Actual
Phase
Phase 1Phase 2
Conditions
Melanoma
Solid Tumors
Interventions
Pembrolizumab
Dabrafenib
Trametinib
Placebo
Countries
Not provided
Protocol Section
Identification Module
NCT ID
NCT02130466
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
3475-022
Secondary IDs
ID
Type
Description
Link
MK-3475-022
Other Identifier
Merck
KEYNOTE-022
Other Identifier
Merck
2015-000681-55
EudraCT Number
Brief Title
A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475-022/KEYNOTE-022)
Official Title
A Phase I/II Study to Assess the Safety and Efficacy of MK-3475 in Combination With Trametinib and Dabrafenib in Subjects With Advanced Melanoma
Acronym
Not provided
Organization
Merck Sharp & Dohme LLCINDUSTRY
Status Module
Record Verification Date
Jun 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
YesNCT02083484No longer available
Start Date
May 29, 2014Actual
Primary Completion Date
Jul 14, 2021Actual
Completion Date
Jul 14, 2021Actual
First Submitted Date
May 1, 2014
First Submission Date that Met QC Criteria
May 1, 2014
First Posted Date
May 5, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 30, 2022
Results First Submitted that Met QC Criteria
Jun 30, 2022
Results First Posted Date
Aug 1, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 30, 2022
Last Update Posted Date
Aug 1, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Merck Sharp & Dohme LLCINDUSTRY
Collaborators
Name
Class
Novartis Pharmaceuticals
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a 5-part dose-finding and preliminary efficacy study of pembrolizumab (Pembro) + dabrafenib (D) + trametinib (T) for participants with advanced melanoma and solid tumors.
Parts 1 and 2 are open-label to find and confirm the maximum tolerated dose (MTD)/maximum administered dose (MAD) for Pembro+D+T. The primary hypothesis (Parts 1 and 2) is that Pembro+D+T is sufficiently well-tolerated to permit clinical investigation.
Part 3 is a double-blind study of Pembro+D+T versus placebo+D+T. The primary study hypothesis (Part 3 only) is that the Pembro+D+T improves progression-free survival (PFS) compared with placebo+D+T.
Part 4 is nonrandomized and open-label and is designed to evaluate the safety and tolerability and identify the MTD or MAD of Pembro+T in participants who have v-raf murine sarcoma viral oncogene homolog B1 [BRAF] mutation-negative (without V600 E or K) melanoma or solid tumors [irrespective of BRAF status]. The primary hypothesis (Part 4) is that Pembro+T is sufficiently well-tolerated to permit clinical investigation.
Part 5 will confirm the dose(s) identified in Part 4 in participants BRAF wild type [without V600E or K] melanoma or solid tumors [irrespective of BRAF status] and will further evaluate the safety and preliminary efficacy (Objective Response Rate [ORR]) of Pembro+T in participants who have BRAF wild type [without V600E or K] melanoma or solid tumors [irrespective of BRAF status]. The primary hypotheses (Part 5) are that Pembro+T is sufficiently well-tolerated at the MTD/MAD to permit further clinical investigation and is effective in attaining objective responses based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator review in participants who have melanoma without BRAF V600 E or K mutations. With Amendment 5 (21-Mar-2019), the Part 5 expansion cohort will not be pursued following the completion of Part 5 dose confirmation.
Parts 1 and 2 of the study may also explore, if needed based on tolerability, the backup combinations of open-label Pembro+T (for BRAF mutation-negative participants) or Pembro+D (for BRAF mutation-positive participants). These will run concurrently with the Pembro+D+T arm.
Detailed Description
Not provided
Conditions Module
Conditions
Melanoma
Solid Tumors
Keywords
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
184Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1:pembrolizumab 2 mg/kg+dabrafenib150 mg+trametinib 2 mg
Experimental
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by intravenous (IV) infusion on Days 1 and 22 of each 6-week cycle (Q6W); 150 mg/day total dabrafenib orally, in a divided dose, twice a day (BID) starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally once a day (QD) starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Dabrafenib
Drug: Trametinib
Part 1:pembrolizumab 2 mg/kg+trametinib 2 mg
Experimental
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 1:pembrolizumab 2 mg/kg+trametinib 1.5 mg
Experimental
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 2:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Experimental
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Pembrolizumab
Biological
IV infusion
Part 1:pembrolizumab 2 mg/kg+dabrafenib150 mg+trametinib 2 mg
Part 1:pembrolizumab 2 mg/kg+trametinib 1.5 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Parts 1, 2, 4, and 5: Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
DLTs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Events were considered a DLT if occurred during the DLT evaluation period and met ≥1 of the following: significant hematologic toxicity; significant Grade ≥3 non-hematologic toxicity not previously identified or known to occur and cannot be controlled with routine supportive measures; drug-related toxicity that results in an interruption of any component of study therapy for >21 consecutive days and cannot be controlled ≤2 weeks from onset; any other Grade ≥2 non-hematological toxicity that is dose limiting with some exceptions; and liver chemistries meeting study stopping guidelines. The DLT evaluable population included all participants in Parts 1, 2, 4, and 5 who received ≥66% of planned treatments during the DLT observation period or discontinued treatment due to a DLT. Per protocol, DLT outcome analysis did not include Part 3.
Up to approximately 6 weeks
Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants Without BRAF V600 E or K Mutations
ORR was defined as the percentage of participants without BRAF V600 E or K mutation who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR based on RECIST 1.1 as assessed by investigator were reported.
Up to approximately 85 months
Part 5: ORR Per RECIST 1.1 as Assessed by Investigator in Participants Without BRAF V600 E or K Mutations or With Solid Tumors Irrespective of BRAF Status
ORR was defined as the percentage of participants without BRAF V600 E or K mutation who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR based on RECIST 1.1 as assessed by investigator were reported.
Secondary Outcomes
Measure
Description
Time Frame
Part 1: ORR Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
ORR was defined as the percentage of participants who had a CR (Disappearance of all target lesions) or a PR (divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR as assessed by the investigator was presented.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma excluding mucosal, or ocular melanoma (or a histologically or cytologically-documented locally-advanced or metastatic solid malignancy in Parts 4 and 5)
At least 1 measurable lesion as defined by RECIST 1.1 on imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI])
For solid tumors other than melanoma, (in Part 4 or 5 [dose confirmation only]), participants must have a malignancy that is incurable and has either: (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the participants and treating physician. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds targeting programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), BRAF, or mitogen-activated protein kinase (MEK). Treatment must end at least 4 weeks prior to randomization
BRAF mutation-positive (V600 E or K) melanoma for Parts 1, 2 and 3, or for Parts 1, 2, 4 and 5 only BRAF mutation-negative (wild type) melanoma with documented progression of ≥1 measurable lesion after prior therapy (if prior therapy was received). The inclusion criterion does not apply to participants with solid tumors in Parts 4 and 5 (dose confirmation only)
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Anticipated life expectancy of at least 3 months
Able to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
Adequate organ function
Provide tissue for biomarker analysis from a newly or recently-obtained biopsy (within 90 days of Study Day 1) of a tumor lesion not previously irradiated
Female participants of non-childbearing potential must be willing to use highly effective contraceptive measures from the Screening Visit (Visit 1) through 120 days after the last dose of study drug; male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug
Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug
Exclusion criteria:
Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study drug
Prior systemic therapy (for participants who are BRAF mutation-positive), or BRAF mutation-negative and has received >1 prior systemic therapy for metastatic melanoma
Prior therapy with compounds targeting PD-1, PD-L1, BRAF, MEK or other molecules in the mitogen-activated protein kinase (MAPK) pathway
BRAF mutation-positive and has received prior systemic therapy with ipilimumab or other anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibodies. The BRAF exclusion criterion does not apply to participants with solid tumor in Parts 4 and 5 (dose confirmation only)
Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or not recovered from clinically significant adverse events due to cancer therapeutics administered more than 4 weeks prior to the first dose of study drug
Expected to require any other form of systemic or localized antineoplastic therapy while in this study
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy
Active central nervous system (CNS) metastases and/or carcinomatous meningitis
Active infection requiring systemic therapy
Active autoimmune disease, or documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
Previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
On chronic systemic steroid therapy (>10 mg/day prednisone or equivalent) within 2 weeks prior to first dose of study drug or on any other form of immunosuppressive medication
History or evidence of cardiovascular risk
Uncorrectable electrolyte abnormalities, long QT syndrome or taking medications known to prolong the QT interval
History of prior or current retinal vein occlusion (RVO)
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, their excipients, and/or dimethyl sulfoxide (DMSO)
Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant
History of (non-infectious) pneumonitis that required steroids or current pneumonitis
Human immunodeficiency virus (HIV)
Hepatitis B or C
Received a live vaccine within 30 days prior to first dose of study drug
Pregnant or breastfeeding or expecting to conceive or father children from the Screening Visit (Visit 1) through 120 days after last dose of study drug
Ribas A, Lawrence D, Atkinson V, Agarwal S, Miller WH Jr, Carlino MS, Fisher R, Long GV, Hodi FS, Tsoi J, Grasso CS, Mookerjee B, Zhao Q, Ghori R, Moreno BH, Ibrahim N, Hamid O. Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma. Nat Med. 2019 Jun;25(6):936-940. doi: 10.1038/s41591-019-0476-5. Epub 2019 Jun 6.
For Parts 1 and 2 of the study the optional pembrolizumab+trametinib arm was added to the study but the optional pembrolizumab+dabrafenib arm was not implemented.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by intravenous (IV) infusion on Days 1 and 22 of each 6-week cycle (Q6W); 150 mg/day total dabrafenib orally, in a divided dose, twice a day (BID) starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally once a day (QD) starting on Day 1 and continuing up until study treatment discontinuation.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Dec 5, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Australia
Canada
Denmark
Israel
Italy
New Zealand
United States
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Biological: Pembrolizumab
Drug: Dabrafenib
Drug: Trametinib
Part 2:pembrolizumab 2 mg/kg+trametinib 1.5 mg
Experimental
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 3:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Experimental
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Dabrafenib
Drug: Trametinib
Part 3:placebo+dabrafenib 150 mg+trametinib 2 mg
Placebo Comparator
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Drug: Dabrafenib
Drug: Trametinib
Drug: Placebo
Part 4:trametinib 2 mg for 4 weeks+pembrolizumab 200 mg+trametinib 2 mg concurrent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 4:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 4:trametinib 1.5 mg for 4 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 4:trametinib 2 mg for 2 weeks+pembrolizumab 200 mg+trametinib 2 mg intermittent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 4:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg intermittent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 5:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 5:trametinib 2 mg for 2 weeks+pembrolizumab 200 mg+trametinib 2 mg intermittent dosing
Experimental
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
Biological: Pembrolizumab
Drug: Trametinib
Part 1:pembrolizumab 2 mg/kg+trametinib 2 mg
Part 2:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Part 2:pembrolizumab 2 mg/kg+trametinib 1.5 mg
Part 3:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Part 4:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Part 4:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg intermittent dosing
Part 4:trametinib 1.5 mg for 4 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Part 4:trametinib 2 mg for 2 weeks+pembrolizumab 200 mg+trametinib 2 mg intermittent dosing
Part 4:trametinib 2 mg for 4 weeks+pembrolizumab 200 mg+trametinib 2 mg concurrent dosing
Part 5:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Part 5:trametinib 2 mg for 2 weeks+pembrolizumab 200 mg+trametinib 2 mg intermittent dosing
MK-3475
KEYTRUDA®
Dabrafenib
Drug
oral capsule
Part 1:pembrolizumab 2 mg/kg+dabrafenib150 mg+trametinib 2 mg
Part 2:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Part 3:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Part 3:placebo+dabrafenib 150 mg+trametinib 2 mg
TAFINLAR®
Trametinib
Drug
oral tablet
Part 1:pembrolizumab 2 mg/kg+dabrafenib150 mg+trametinib 2 mg
Part 1:pembrolizumab 2 mg/kg+trametinib 1.5 mg
Part 1:pembrolizumab 2 mg/kg+trametinib 2 mg
Part 2:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Part 2:pembrolizumab 2 mg/kg+trametinib 1.5 mg
Part 3:pembrolizumab 2 mg/kg+dabrafenib 150 mg+trametinib 2 mg
Part 3:placebo+dabrafenib 150 mg+trametinib 2 mg
Part 4:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Part 4:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg intermittent dosing
Part 4:trametinib 1.5 mg for 4 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Part 4:trametinib 2 mg for 2 weeks+pembrolizumab 200 mg+trametinib 2 mg intermittent dosing
Part 4:trametinib 2 mg for 4 weeks+pembrolizumab 200 mg+trametinib 2 mg concurrent dosing
Part 5:trametinib 1.5 mg for 2 weeks+pembrolizumab 200 mg+trametinib 1.5 mg concurrent dosing
Part 5:trametinib 2 mg for 2 weeks+pembrolizumab 200 mg+trametinib 2 mg intermittent dosing
MEKINIST®
Placebo
Drug
IV infusion
Part 3:placebo+dabrafenib 150 mg+trametinib 2 mg
Up to approximately 85 months
Part 3: Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
PFS was defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurred first, based on RECIST 1.1 by investigator review. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS was analyzed using the Kaplan-Meier method and was reported in months. Statistical analysis used a Cox regression model with treatment as a covariate and stratified by Eastern Cooperative Oncology Group performance status and Lactate Dehydrogenase.
Up to approximately 85 months
Parts 1, 2, 4, and 5: Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. The number of participants who experienced an AE was reported. Per protocol, AE outcome analysis did not include Part 3.
Up to approximately 32 months
Parts 1, 2, 4, and 5: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. The number of participants who discontinued study treatment due to an AE was reported. Per protocol, discontinuation outcome analysis did not include Part 3.
Up to approximately 29 months
Up to approximately 85 months
Part 2: ORR Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
ORR was defined as the percentage of participants who had a CR (Disappearance of all target lesions) or a PR (divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR as assessed by the investigator was presented.
Up to approximately 85 months
Part 3: ORR Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
ORR was defined as the percentage of participants who had a CR (Disappearance of all target lesions) or a PR (divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR as assessed by the investigator was presented.
Up to approximately 85 months
Part 3: Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
For participants who demonstrated a confirmed CR (Disappearance of all target lesions) or a confirmed PR (divided by VGPR [>60% tumor reduction] and MPR [>30-≤60% tumor reduction]) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD). Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by the investigator was analyzed using Kaplan-Meier method and reported in months.
Up to approximately 85 months
Part 3: Overall Survival (OS) in Participants With BRAF V600 E or K Mutations
OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and was reported in months. Statistical analysis used a Cox regression model with treatment as a covariate and stratified by Eastern Cooperative Oncology Group performance status and Lactate Dehydrogenase.
Up to approximately 85 months
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 2 mg/kg pembrolizumab in combination with dabrafenib and/or trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. All participants who received pembrolizumab from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of pembrolizumab is presented.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 2 mg/kg pembrolizumab in combination with dabrafenib and trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. The Cmax of pembrolizumab is presented.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 200 mg pembrolizumab in combination with trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. The Cmax of pembrolizumab is presented.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 200 mg pembrolizumab in combination with trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. The Cmax of pembrolizumab is presented.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 2 mg/kg pembrolizumab administered in combination with dabrafenib and/or trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. All participants who received pembrolizumab from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of pembrolizumab is presented.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 2 mg/kg pembrolizumab administered in combination with dabrafenib and trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. The Ctrough of pembrolizumab is presented.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 200 mg pembrolizumab administered in combination with trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. The Ctrough of pembrolizumab is presented.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 200 mg pembrolizumab administered in combination with trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. The Ctrough of pembrolizumab is presented.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of dabrafenib observed after administration of 150 mg dabrafenib in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Cmax of dabrafenib. All participants who received dabrafenib from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of dabrafenib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Cmax was defined as the maximum concentration of dabrafenib observed after administration of 150 mg dabrafenib in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Cmax of dabrafenib. The Cmax of dabrafenib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Cmax was defined as the maximum concentration of dabrafenib observed after administration of 150 mg dabrafenib in combination with saline placebo and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Cmax of dabrafenib. The Cmax of dabrafenib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of dabrafenib that occurred immediately prior to the next dose of 150 mg dabrafenib administered in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of dabrafenib. All participants who received dabrafenib from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of dabrafenib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Ctrough was defined as the lowest concentration of dabrafenib that occurred immediately prior to the next dose of 150 mg dabrafenib administered in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of dabrafenib. The Ctrough of dabrafenib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Ctrough was defined as the lowest concentration of dabrafenib that occurred immediately prior to the next dose of 150 mg dabrafenib administered in combination with saline placebo and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of dabrafenib. The Ctrough of dabrafenib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. All participants who received 2 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of trametinib observed after administration of 1.5 mg trametinib in combination with 2 mg/kg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. All participants who received 1.5 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with saline placebo and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Cmax was defined as the maximum concentration of trametinib observed after administration of 1.5 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Maximum Concentration (Cmax) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Cmax was defined as the maximum concentration of trametinib observed after administration of 1.5 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. All participants who received 2 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 1.5 mg trametinib administered in combination with 2 mg/kg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. All participants who received 1.5 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with saline placebo and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 1.5 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Trough Concentration (Ctrough) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 1.5 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of dabrafenib, defined as the volume of plasma from which dabrafenib is eliminated per unit time following dabrafenib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of dabrafenib, defined as the volume of plasma from which dabrafenib is eliminated per unit time following dabrafenib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of dabrafenib, defined as the volume of plasma from which dabrafenib is eliminated per unit time following dabrafenib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Clearance (Cl) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of dabrafenib, defined as the theoretical volume that would be necessary to contain the total amount of administered dabrafenib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of dabrafenib, defined as the theoretical volume that would be necessary to contain the total amount of administered dabrafenib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of dabrafenib, defined as the theoretical volume that would be necessary to contain the total amount of administered dabrafenib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Volume of Distribution (Vc) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
Result
Ascierto PA, Ferrucci PF, Fisher R, Del Vecchio M, Atkinson V, Schmidt H, Schachter J, Queirolo P, Long GV, Di Giacomo AM, Svane IM, Lotem M, Bar-Sela G, Couture F, Mookerjee B, Ghori R, Ibrahim N, Moreno BH, Ribas A. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat Med. 2019 Jun;25(6):941-946. doi: 10.1038/s41591-019-0448-9. Epub 2019 Jun 6.
Maio M, Carlino MS, Joshua AM, McWhirter E, Ribas A, Ascierto PA, Miller WH Jr, Butler MO, Ferrucci PF, Zielinski RR, Del Vecchio M, Gasal E, Ghori R, Diede SJ, Croydon E, Hamid O. KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. Eur J Cancer. 2022 Jan;160:1-11. doi: 10.1016/j.ejca.2021.09.024. Epub 2021 Nov 17.
FG001
Part 1:Pembrolizumab 2 mg/kg+Trametinib 2 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG002
Part 1:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG003
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG004
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG005
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG006
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG007
Part 4:4 Weeks Trametinib (Tra) 2mg; Pembrolizumab+Tra 2mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG008
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG009
Part 4:4 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG010
Part 4:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
FG011
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
FG012
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
FG013
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
FG0007 subjects
FG0013 subjects
FG0022 subjects
FG0038 subjects
FG0042 subjects
FG00560 subjects
FG00660 subjects
FG0073 subjects
FG0084 subjects
FG0095 subjects
FG0106 subjects
FG0113 subjects
FG01212 subjects
FG0139 subjects
Treated
FG0007 subjects
FG0013 subjects
FG0022 subjects
FG0038 subjects
FG0042 subjects
FG00560 subjects
FG00660 subjects
FG0073 subjects
FG0084 subjects
FG0095 subjects
FG0106 subjects
FG0113 subjects
FG01212 subjects
FG0139 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
NOT COMPLETED
FG0007 subjects
FG0013 subjects
FG0022 subjects
FG0038 subjects
FG0042 subjects
FG00560 subjects
FG00660 subjects
FG0073 subjects
FG0084 subjects
FG0095 subjects
FG0106 subjects
FG0113 subjects
FG01212 subjects
FG0139 subjects
Type
Comment
Reasons
Death
FG0004 subjects
FG0011 subjects
FG0021 subjects
FG0033 subjects
FG0042 subjects
FG00530 subjects
FG00645 subjects
FG0072 subjects
FG0083 subjects
FG0094 subjects
FG0105 subjects
FG0113 subjects
FG01211 subjects
FG0137 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Participation in Study Discontinued by Sponsor
FG0001 subjects
FG0012 subjects
FG0021 subjects
FG0035 subjects
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
All participants who received ≥1 dose of study treatment
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by intravenous (IV) infusion on Days 1 and 22 of each 6-week cycle (Q6W); 150 mg/day total dabrafenib orally, in a divided dose, twice a day (BID) starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally once a day (QD) starting on Day 1 and continuing up until study treatment discontinuation.
BG001
Part 1:Pembrolizumab 2 mg/kg+Trametinib 2 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG002
Part 1:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG003
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG004
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG005
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG006
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG007
Part 4:4 Weeks Trametinib (Tra) 2mg; Pembrolizumab+Tra 2mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG008
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG009
Part 4:4 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG010
Part 4:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
BG011
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
BG012
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
BG013
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
BG014
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0007
BG0013
BG0022
BG0038
BG0042
BG00560
BG00660
BG0073
BG0084
BG0095
BG0106
BG0113
BG01212
BG0139
BG014184
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00052.0± 14.0
BG00154.0± 15.7
BG00268.0± 2.8
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0003
BG0010
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
BRAF Mutation Status
BRAF mutation testing was required for study inclusion and was done using methodology that detects both V600E and V600K mutations. Tumors that were BRAF mutation positive (V600 E or K) were eligible for treatment with pembrolizumab + trametinib + dabrafenib or trametinib + dabrafenib. Tumors that were BRAF mutation negative (wild type) were eligible for treatment with pembrolizumab + trametinib.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Mutant (BRAF Positive)
BG0007
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Parts 1, 2, 4, and 5: Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
DLTs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Events were considered a DLT if occurred during the DLT evaluation period and met ≥1 of the following: significant hematologic toxicity; significant Grade ≥3 non-hematologic toxicity not previously identified or known to occur and cannot be controlled with routine supportive measures; drug-related toxicity that results in an interruption of any component of study therapy for >21 consecutive days and cannot be controlled ≤2 weeks from onset; any other Grade ≥2 non-hematological toxicity that is dose limiting with some exceptions; and liver chemistries meeting study stopping guidelines. The DLT evaluable population included all participants in Parts 1, 2, 4, and 5 who received ≥66% of planned treatments during the DLT observation period or discontinued treatment due to a DLT. Per protocol, DLT outcome analysis did not include Part 3.
The DLT evaluable population included all participants in Parts 1, 2, 4, and 5 who received at least 66% of all planned treatments during the 6-week DLT observation period or who discontinued treatment due to a DLT.
Posted
Count of Participants
Participants
Up to approximately 6 weeks
ID
Title
Description
OG000
Part 1:Pembrolizumab 2 mg/kg+dabrafenib150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 1:Pembrolizumab 2 mg/kg+Trametinib 2 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG002
Part 1:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG003
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG004
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Units
Counts
Participants
OG0007
OG0013
OG0022
OG003
Title
Denominators
Categories
Title
Measurements
OG0001
OG0011
OG0021
OG003
Primary
Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants Without BRAF V600 E or K Mutations
ORR was defined as the percentage of participants without BRAF V600 E or K mutation who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR based on RECIST 1.1 as assessed by investigator were reported.
All enrolled participants without BRAF V600 E or K mutations in Part 2
Posted
Number
95% Confidence Interval
Percentage of Participants
Up to approximately 85 months
ID
Title
Description
OG000
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Primary
Part 5: ORR Per RECIST 1.1 as Assessed by Investigator in Participants Without BRAF V600 E or K Mutations or With Solid Tumors Irrespective of BRAF Status
ORR was defined as the percentage of participants without BRAF V600 E or K mutation who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR based on RECIST 1.1 as assessed by investigator were reported.
All enrolled participants without BRAF V600 E or K mutations in Part 5
Posted
Number
95% Confidence Interval
Percentage of Participants
Up to approximately 85 months
ID
Title
Description
OG000
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
Primary
Part 3: Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
PFS was defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurred first, based on RECIST 1.1 by investigator review. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS was analyzed using the Kaplan-Meier method and was reported in months. Statistical analysis used a Cox regression model with treatment as a covariate and stratified by Eastern Cooperative Oncology Group performance status and Lactate Dehydrogenase.
All randomized participants with BRAF V600 E or K mutations in Part 3
Posted
Median
95% Confidence Interval
Months
Up to approximately 85 months
ID
Title
Description
OG000
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Primary
Parts 1, 2, 4, and 5: Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. The number of participants who experienced an AE was reported. Per protocol, AE outcome analysis did not include Part 3.
All participants who received at least one dose of study treatment in Parts 1, 2, 4, and 5.
Posted
Count of Participants
Participants
Up to approximately 32 months
ID
Title
Description
OG000
Part 1:Pembrolizumab 2 mg/kg+dabrafenib150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 1:Pembrolizumab 2 mg/kg+Trametinib 2 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Primary
Parts 1, 2, 4, and 5: Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. The number of participants who discontinued study treatment due to an AE was reported. Per protocol, discontinuation outcome analysis did not include Part 3.
All participants who received at least one dose of study treatment in Parts 1, 2, 4, and 5.
Posted
Count of Participants
Participants
Up to approximately 29 months
ID
Title
Description
OG000
Part 1:Pembrolizumab 2 mg/kg+dabrafenib150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 1:Pembrolizumab 2 mg/kg+Trametinib 2 mg
Secondary
Part 1: ORR Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
ORR was defined as the percentage of participants who had a CR (Disappearance of all target lesions) or a PR (divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR as assessed by the investigator was presented.
All enrolled participants with BRAF V600 E or K mutations in Part 1
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 85 months
ID
Title
Description
OG000
Part 1:Pembrolizumab 2 mg/kg+dabrafenib150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Part 2: ORR Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
ORR was defined as the percentage of participants who had a CR (Disappearance of all target lesions) or a PR (divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR as assessed by the investigator was presented.
All enrolled participants with BRAF V600 E or K mutations in Part 2
Posted
Number
95% Confidence Interval
Percentage of Participants
Up to approximately 85 months
ID
Title
Description
OG000
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Part 3: ORR Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
ORR was defined as the percentage of participants who had a CR (Disappearance of all target lesions) or a PR (divided into very good partial response [VGPR; >60% tumor reduction] and moderate partial response [MPR; >30-≤60% tumor reduction]) per RECIST 1.1 as assessed by investigator. The percentage of participants who experienced a CR or PR as assessed by the investigator was presented.
All randomized participants with BRAF V600 E or K mutations in Part 3
Posted
Number
95% Confidence Interval
Percentage of Participants
Up to approximately 85 months
ID
Title
Description
OG000
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Secondary
Part 3: Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator in Participants With BRAF V600 E or K Mutations
For participants who demonstrated a confirmed CR (Disappearance of all target lesions) or a confirmed PR (divided by VGPR [>60% tumor reduction] and MPR [>30-≤60% tumor reduction]) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD). Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by the investigator was analyzed using Kaplan-Meier method and reported in months.
All randomized participants with BRAF V600 E or K mutations who had a confirmed CR or PR in Part 3
Posted
Median
95% Confidence Interval
Months
Up to approximately 85 months
ID
Title
Description
OG000
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Secondary
Part 3: Overall Survival (OS) in Participants With BRAF V600 E or K Mutations
OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and was reported in months. Statistical analysis used a Cox regression model with treatment as a covariate and stratified by Eastern Cooperative Oncology Group performance status and Lactate Dehydrogenase.
All randomized participants with BRAF V600 E or K mutations in Part 3
Posted
Median
95% Confidence Interval
Months
Up to approximately 85 months
ID
Title
Description
OG000
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG001
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Secondary
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 2 mg/kg pembrolizumab in combination with dabrafenib and/or trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. All participants who received pembrolizumab from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of pembrolizumab is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 2 mg/kg pembrolizumab and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+1.5/2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with dabrafenib and 2 mg trametinib OR 2 mg/kg pembrolizumab and 1.5 or 2 mg trametinib (without dabrafenib) Q6W continuing up until study treatment discontinuation.
Units
Counts
Secondary
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 2 mg/kg pembrolizumab in combination with dabrafenib and trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. The Cmax of pembrolizumab is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 2 mg/kg pembrolizumab and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 200 mg pembrolizumab in combination with trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. The Cmax of pembrolizumab is presented.
The analysis population consisted of all participants from Part 4 who received ≥1 dose of 200 mg pembrolizumab and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Cmax was defined as the maximum concentration of pembrolizumab observed after administration of 200 mg pembrolizumab in combination with trametinib. Blood samples were collected at multiple time points to estimate the Cmax of pembrolizumab. The Cmax of pembrolizumab is presented.
The analysis population consisted of all participants from Part 5 who received ≥1 dose of 200 mg pembrolizumab and who had available data for the analysis of Cmax. There were no participants with data available for the analysis of Cmax in Part 5.
Posted
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 2 mg/kg pembrolizumab administered in combination with dabrafenib and/or trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. All participants who received pembrolizumab from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of pembrolizumab is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 2 mg/kg pembrolizumab and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+1.5/2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with dabrafenib and 2 mg trametinib OR 2 mg/kg pembrolizumab and 1.5 or 2 mg trametinib (without dabrafenib) Q6W continuing up until study treatment discontinuation.
Secondary
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 2 mg/kg pembrolizumab administered in combination with dabrafenib and trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. The Ctrough of pembrolizumab is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 2 mg/kg pembrolizumab and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 200 mg pembrolizumab administered in combination with trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. The Ctrough of pembrolizumab is presented.
The analysis population consisted of all participants from Part 4 who received ≥1 dose of 200 mg pembrolizumab and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Ctrough was defined as the lowest concentration of pembrolizumab that occurred immediately prior to the next dose of 200 mg pembrolizumab administered in combination with trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of pembrolizumab. The Ctrough of pembrolizumab is presented.
The analysis population consisted of all participants from Part 5 who received ≥1 dose of 200 mg pembrolizumab and who had available data for the analysis of Ctrough. There were no participants with data available for the analysis of Ctrough in Part 5.
Posted
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of dabrafenib observed after administration of 150 mg dabrafenib in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Cmax of dabrafenib. All participants who received dabrafenib from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of dabrafenib is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 150 mg dabrafenib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab and/or Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab and 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Cmax was defined as the maximum concentration of dabrafenib observed after administration of 150 mg dabrafenib in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Cmax of dabrafenib. The Cmax of dabrafenib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 150 mg dabrafenib and pembrolizumab and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Concentration (Cmax) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Cmax was defined as the maximum concentration of dabrafenib observed after administration of 150 mg dabrafenib in combination with saline placebo and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Cmax of dabrafenib. The Cmax of dabrafenib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 150 mg dabrafenib and placebo and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of dabrafenib that occurred immediately prior to the next dose of 150 mg dabrafenib administered in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of dabrafenib. All participants who received dabrafenib from Parts 1 and 2 were handled as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of dabrafenib is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 150 mg dabrafenib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab and/or Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Ctrough was defined as the lowest concentration of dabrafenib that occurred immediately prior to the next dose of 150 mg dabrafenib administered in combination with 2 mg/kg pembrolizumab and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of dabrafenib. The Ctrough of dabrafenib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 150 mg dabrafenib and pembrolizumab and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Ctrough was defined as the lowest concentration of dabrafenib that occurred immediately prior to the next dose of 150 mg dabrafenib administered in combination with saline placebo and 2 mg trametinib. Blood samples were collected at multiple time points to estimate the Ctrough of dabrafenib. The Ctrough of dabrafenib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 150 mg dabrafenib and placebo and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. All participants who received 2 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of trametinib is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 2 mg trametinib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Cmax was defined as the maximum concentration of trametinib observed after administration of 1.5 mg trametinib in combination with 2 mg/kg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. All participants who received 1.5 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Cmax of trametinib is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 1.5 mg trametinib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+1.5 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 1.5 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 2 mg trametinib and pembrolizumab and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with saline placebo and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 2 mg trametinib and placebo and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
The analysis population consisted of all participants from Part 4 who received ≥1 dose of 2 mg trametinib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Cmax was defined as the maximum concentration of trametinib observed after administration of 1.5 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
The analysis population consisted of all participants from Part 4 who received ≥1 dose of 1.5 mg trametinib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Cmax was defined as the maximum concentration of trametinib observed after administration of 2 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
The analysis population consisted of all participants from Part 5 who received ≥1 dose of 2 mg trametinib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Maximum Concentration (Cmax) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Cmax was defined as the maximum concentration of trametinib observed after administration of 1.5 mg trametinib in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Cmax of trametinib. The Cmax of trametinib is presented.
The analysis population consisted of all participants from Part 5 who received ≥1 dose of 1.5 mg trametinib and who had available data for the analysis of Cmax.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. All participants who received 2 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of trametinib is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 2 mg trametinib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 1.5 mg trametinib administered in combination with 2 mg/kg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. All participants who received 1.5 mg trametinib from Parts 1 and 2 were treated as a single arm and analyzed as a single study population for this outcome measure since Part 2 was the dose confirmation phase of Part 1. The Ctrough of trametinib is presented.
The analysis population consisted of all participants pooled from Parts 1 and 2 who received ≥1 dose of 1.5 mg trametinib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+1.5 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 1.5 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 2 mg/kg pembrolizumab and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 2 mg trametinib and pembrolizumab and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with saline placebo and 150 mg dabrafenib. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
The analysis population consisted of all participants from Part 3 who received ≥1 dose of 2 mg trametinib and placebo and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
The analysis population consisted of all participants from Part 4 who received ≥1 dose of 2 mg trametinib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 1.5 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
The analysis population consisted of all participants from Part 4 who received ≥1 dose of 1.5 mg trametinib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 2 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
The analysis population consisted of all participants from Part 5 who received ≥1 dose of 2 mg trametinib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Trough Concentration (Ctrough) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Ctrough was defined as the lowest concentration of trametinib that occurred immediately prior to the next dose of 1.5 mg trametinib administered in combination with 200 mg pembrolizumab. Blood samples were collected at multiple time points to estimate the Ctrough of trametinib. The Ctrough of trametinib is presented.
The analysis population consisted of all participants from Part 5 who received ≥1 dose of 1.5 mg trametinib and who had available data for the analysis of Ctrough.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
As specified by the protocol, the Cl of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+1.5/2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with dabrafenib and 2 mg trametinib OR 2 mg/kg pembrolizumab and 1.5 or 2 mg trametinib (without dabrafenib) Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Clearance (Cl) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
As specified by the protocol, the Cl of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Clearance (Cl) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
As specified by the protocol, the Cl of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Secondary
Clearance (Cl) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Cl of pembrolizumab, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following pembrolizumab administration. This analysis was not performed.
As specified by the protocol, the Cl of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Clearance (Cl) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of dabrafenib, defined as the volume of plasma from which dabrafenib is eliminated per unit time following dabrafenib administration. This analysis was not performed.
As specified by the protocol, the Cl of dabrafenib was only to be analyzed if required and no data were collected since, by the time of final analysis, dabrafenib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of dabrafenib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of dabrafenib, defined as the volume of plasma from which dabrafenib is eliminated per unit time following dabrafenib administration. This analysis was not performed.
As specified by the protocol, the Cl of dabrafenib was only to be analyzed if required and no data were collected since, by the time of final analysis, dabrafenib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of dabrafenib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of dabrafenib, defined as the volume of plasma from which dabrafenib is eliminated per unit time following dabrafenib administration. This analysis was not performed.
As specified by the protocol, the Cl of dabrafenib was only to be analyzed if required and no data were collected since, by the time of final analysis, dabrafenib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of dabrafenib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+1.5 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 1.5 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Clearance (Cl) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Clearance (Cl) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Clearance (Cl) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Clearance (Cl) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Cl of trametinib, defined as the volume of plasma from which trametinib is eliminated per unit time following trametinib administration. This analysis was not performed.
As specified by the protocol, the Cl of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and/or Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+1.5/2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with dabrafenib and 2 mg trametinib OR 2 mg/kg pembrolizumab and 1.5 or 2 mg trametinib (without dabrafenib) Q6W continuing up until study treatment discontinuation.
Units
Counts
Secondary
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 2 mg/kg Pembrolizumab in Combination With Dabrafenib and Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 1: predose, postdose, 24 - 96 hours (hrs) postdose; Cycle 1 Day 22: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Secondary
Volume of Distribution (Vc) of Pembrolizumab Following Administration of 200 mg Pembrolizumab in Combination With Trametinib in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Vc of pembrolizumab, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of pembrolizumab was only to be analyzed if required and no data were collected since, by the time of final analysis, pembrolizumab pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of pembrolizumab characterized across indications.
Posted
Cycle 1 Day 15: predose, postdose, 24 - 96 hrs postdose; Cycle 1 Day 36: predose, postdose; Cycle 2 Day 1: predose, postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+Trametinib
Participants received 2 mg or 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of dabrafenib, defined as the theoretical volume that would be necessary to contain the total amount of administered dabrafenib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of dabrafenib was only to be analyzed if required and no data were collected since, by the time of final analysis, dabrafenib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of dabrafenib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With 2 mg/kg Pembrolizumab and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of dabrafenib, defined as the theoretical volume that would be necessary to contain the total amount of administered dabrafenib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of dabrafenib was only to be analyzed if required and no data were collected since, by the time of final analysis, dabrafenib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of dabrafenib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Dabrafenib Following Administration of 150 mg Dabrafenib in Combination With Placebo and 2 mg Trametinib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of dabrafenib, defined as the theoretical volume that would be necessary to contain the total amount of administered dabrafenib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of dabrafenib was only to be analyzed if required and no data were collected since, by the time of final analysis, dabrafenib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of dabrafenib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+Dabrafenib+2 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 2 mg/kg Pembrolizumab in Participants Pooled From Parts 1 and 2
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Pooled Parts 1+2:Pembrolizumab+1.5 mg Trametinib
Participants pooled from Parts 1 and 2 received 2 mg/kg pembrolizumab in combination with 1.5 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With 2 mg/kg Pembrolizumab and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: 2 mg/kg Pembrolizumab+Dabrafenib+Trametinib
Participants received 2 mg/kg pembrolizumab in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With Placebo and 150 mg Dabrafenib in Participants From Part 3
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 22: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 3: Placebo+Dabrafenib+Trametinib
Participants received saline placebo in combination with 150 mg dabrafenib and 2 mg trametinib Q6W continuing up until study treatment discontinuation.
Units
Counts
Participants
OG000
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 1.5 mg Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 4
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 4: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 or 4 weeks (depending on treatment regimen). Starting with Week 3 or 5 (depending on initial trametinib interval), participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 2 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+2 mg Trametinib
Participants received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 2 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Secondary
Volume of Distribution (Vc) of Trametinib Following Administration of 1.5 mg of Trametinib in Combination With 200 mg Pembrolizumab in Participants From Part 5
Blood samples were to be collected at pre-specified time points for analysis of the Vc of trametinib, defined as the theoretical volume that would be necessary to contain the total amount of administered trametinib at the same concentration that it is observed in the blood plasma. This analysis was not performed.
As specified by the protocol, the Vc of trametinib was only to be analyzed if required and no data were collected since, by the time of final analysis, trametinib pharmacokinetics (PK) in melanoma participants had been well characterized and found to be consistent with the overall clinical pharmacology of trametinib characterized across indications.
Posted
Cycle 1 Day 36: predose, postdose, 4 - 6 hrs postdose. Each cycle is a 21-day cycle.
ID
Title
Description
OG000
Part 5: 200 mg Pembrolizumab+1.5 mg Trametinib
Participants received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent or concurrent dose schedule of 1.5 mg trametinib orally QD continuing up until study treatment discontinuation.
Units
Counts
Participants
Time Frame
Up to approximately 85 months
Description
All-cause mortality=all randomized participants and adverse events (AE)=all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression, malignant neoplasm progression, and disease progression not related to treatment were excluded.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by intravenous (IV) infusion on Days 1 and 22 of each 6-week cycle (Q6W); 150 mg/day total dabrafenib orally, in a divided dose, twice a day (BID) starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally once a day (QD) starting on Day 1 and continuing up until study treatment discontinuation.
4
7
1
7
7
7
EG001
Part 1:Pembrolizumab 2 mg/kg+Trametinib 2 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
1
3
0
3
3
3
EG002
Part 1:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
1
2
1
2
2
2
EG003
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
3
8
3
8
8
8
EG004
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
2
2
1
2
2
2
EG005
Part 3:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
31
60
36
60
60
60
EG006
Part 3:Placebo+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
45
60
20
60
58
60
EG007
Part 4:4 Weeks Trametinib (Tra) 2mg; Pembrolizumab+Tra 2mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
2
3
1
3
3
3
EG008
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
3
4
1
4
4
4
EG009
Part 4:4 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
4
5
4
5
5
5
EG010
Part 4:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
5
6
4
6
6
6
EG011
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
3
3
1
3
3
3
EG012
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
11
12
4
12
11
12
EG013
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
7
9
2
9
9
9
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG0030 events0 affected8 at risk
EG0040 events0 affected2 at risk
EG0050 events0 affected60 at risk
EG0060 events0 affected60 at risk
EG0071 events1 affected3 at risk
EG0080 events0 affected4 at risk
EG0090 events0 affected5 at risk
EG0101 events1 affected6 at risk
EG0110 events0 affected3 at risk
EG0120 events0 affected12 at risk
EG0130 events0 affected9 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Mitral valve incompetence
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypophysitis
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Detachment of retinal pigment epithelium
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Retinal detachment
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Uveitis
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Discoloured vomit
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lip swelling
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Chills
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Death
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Influenza like illness
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Mucosal haemorrhage
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oedema peripheral
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Drug-induced liver injury
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Immune-mediated hepatitis
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Abdominal infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Bacterial sepsis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lymphangitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Meningitis aseptic
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Parotitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Peritonitis bacterial
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumonia chlamydial
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sepsis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Septic shock
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Streptococcal infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tubo-ovarian abscess
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tendon rupture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Amylase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lipase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Diabetes mellitus
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Fluid retention
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Myositis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Angiosarcoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Bowen's disease
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Skin angiosarcoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Acute motor axonal neuropathy
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Haemorrhagic stroke
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Peripheral motor neuropathy
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Renal impairment
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tubulointerstitial nephritis
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumomediastinum
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tonsillar hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Arterial thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypertension
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypotension
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG0031 events1 affected8 at risk
EG0040 events0 affected2 at risk
EG00513 events8 affected60 at risk
EG0063 events3 affected60 at risk
EG0070 events0 affected3 at risk
EG0080 events0 affected4 at risk
EG0090 events0 affected5 at risk
EG0103 events3 affected6 at risk
EG0111 events1 affected3 at risk
EG0126 events6 affected12 at risk
EG0131 events1 affected9 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Atrioventricular block
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Left ventricular dysfunction
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cerumen impaction
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Deafness unilateral
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Ear discomfort
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Middle ear effusion
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tympanic membrane disorder
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypopituitarism
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cataract
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Chorioretinal disorder
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Chorioretinopathy
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dry eye
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Eyelid rash
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Iridocyclitis
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Keratitis
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Ocular hyperaemia
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Papilloedema
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Periorbital oedema
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Periorbital swelling
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Photophobia
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Retinopathy
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Uveitis
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vision blurred
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Visual field defect
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Visual impairment
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vitreous adhesions
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vitreous detachment
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Angular cheilitis
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Change of bowel habit
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0013 events1 affected3 at risk
EG0022 events2 affected2 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0009 events5 affected7 at risk
EG0016 events2 affected3 at risk
EG0025 events2 affected2 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Frequent bowel movements
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Glossodynia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Large intestine perforation
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lip blister
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lip disorder
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Lip oedema
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lip pain
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lip ulceration
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0003 events3 affected7 at risk
EG0017 events3 affected3 at risk
EG0022 events1 affected2 at risk
EG003
Oral disorder
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rectal tenesmus
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0013 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tongue disorder
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tongue oedema
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0011 events1 affected3 at risk
EG0022 events2 affected2 at risk
EG003
Asthenia
General disorders
MedDRA 24.0
Systematic Assessment
EG0003 events3 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Axillary pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Catheter site pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Chest pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Chills
General disorders
MedDRA 24.0
Systematic Assessment
EG00021 events6 affected7 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Face oedema
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Facial pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Fatigue
General disorders
MedDRA 24.0
Systematic Assessment
EG0005 events4 affected7 at risk
EG0011 events1 affected3 at risk
EG0022 events2 affected2 at risk
EG003
Feeling abnormal
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Feeling cold
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Feeling hot
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Generalised oedema
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Impaired healing
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Influenza like illness
General disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Localised oedema
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Malaise
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Medical device site rash
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oedema peripheral
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0018 events3 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Peripheral swelling
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Pyrexia
General disorders
MedDRA 24.0
Systematic Assessment
EG00023 events7 affected7 at risk
EG0013 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Swelling
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Temperature intolerance
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Autoimmune hepatitis
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cystitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Ear infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Fungal infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Genital herpes
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Gingivitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Herpes virus infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Influenza
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oral fungal infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Paronychia
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumonia klebsiella
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pustule
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Rash pustular
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Accidental overdose
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Back injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Bone contusion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Meniscus injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Mouth injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Wound haemorrhage
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Wound secretion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0005 events3 affected7 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Amylase abnormal
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Amylase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0005 events3 affected7 at risk
EG0013 events3 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood cholesterol increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0004 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0022 events1 affected2 at risk
EG003
Blood glucose increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood iron decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood potassium increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Blood uric acid increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Body temperature increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
C-reactive protein abnormal
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0022 events1 affected2 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Lipase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Liver function test abnormal
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0007 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neutrophil count increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Platelet count decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Procalcitonin increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Transaminases increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Troponin I increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Troponin increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Urobilinogen urine increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Weight decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Weight increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cachexia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0004 events3 affected7 at risk
EG0012 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Polydipsia
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0006 events3 affected7 at risk
EG0012 events2 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0003 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Joint instability
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Limb discomfort
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Limb mass
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0003 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neck mass
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Osteopenia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rotator cuff syndrome
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Winged scapula
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events1 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Melanocytic naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0003 events3 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Dizziness postural
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
External compression headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Head discomfort
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0007 events5 affected7 at risk
EG0014 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperaesthesia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyposmia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Migraine
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Peroneal nerve palsy
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Seizure
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Syncope
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Taste disorder
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Tremor
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Depression
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected2 at risk
EG003
Bladder spasm
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hydronephrosis
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Urinary tract pain
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Adnexa uteri mass
Reproductive system and breast disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Benign prostatic hyperplasia
Reproductive system and breast disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Erectile dysfunction
Reproductive system and breast disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Atelectasis
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0003 events3 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0013 events2 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Laryngeal inflammation
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Lung consolidation
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Nasal ulcer
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Painful respiration
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rales
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rhinalgia
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rhinitis atrophic
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Sinus pain
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Throat irritation
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected7 at risk
EG0014 events3 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Drug eruption
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events1 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Erythema multiforme
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Erythema nodosum
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG00010 events3 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Macule
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Nail disorder
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0007 events3 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pain of skin
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Palmar erythema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0006 events2 affected7 at risk
EG0015 events3 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Psoriasis
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Purpura
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0008 events3 affected7 at risk
EG0015 events2 affected3 at risk
EG0023 events1 affected2 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rash follicular
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Scab
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0014 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Skin exfoliation
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0013 events2 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Skin fissures
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Skin haemorrhage
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Vitiligo
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Xeroderma
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Axillary vein thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Flushing
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hot flush
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypertension
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Hypotension
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected7 at risk
EG0011 events1 affected3 at risk
EG0021 events1 affected2 at risk
EG003
Lymphoedema
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Phlebitis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected2 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Point of Contact
Title
Organization
Phone
Extension
Email
Senior Vice President, Global Clinical Development
Part 4:4 Weeks Trametinib (Tra) 2mg; Pembrolizumab+Tra 2mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG006
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG007
Part 4:4 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG008
Part 4:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
OG009
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
OG010
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG011
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
8
OG0042
OG0053
OG0064
OG0075
OG0086
OG0093
OG01012
OG0119
2
OG0041
OG0052
OG0060
OG0070
OG0082
OG0090
OG0104
OG0112
2
Title
Denominators
Categories
Title
Measurements
OG00050.0(1.3 to 98.7)
Units
Counts
Participants
OG00012
OG0019
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 26.5)
OG00133.3(7.5 to 70.1)
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Units
Counts
Participants
OG00060
OG00160
Title
Denominators
Categories
Title
Measurements
OG00017.0(11.3 to NA)NA = Upper limit for PFS not reached at time of data cut-off due to insufficient number of participants with an event.
OG0019.9(6.7 to 15.6)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
0.46
2-Sided
95
0.29
0.74
Cox regression model
Other
OG002
Part 1:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG003
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG004
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG005
Part 4:4 Weeks Trametinib (Tra) 2mg; Pembrolizumab+Tra 2mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG006
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG007
Part 4:4 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG008
Part 4:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
OG009
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
OG010
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG011
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
Units
Counts
Participants
OG0007
OG0013
OG0022
OG0038
OG0042
OG0053
OG0064
OG0075
OG0086
OG0093
OG01012
OG0119
Title
Denominators
Categories
Title
Measurements
OG0007
OG0013
OG0022
OG0038
OG0042
OG0053
OG0064
OG0075
OG0086
OG0093
OG01011
OG0119
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG002
Part 1:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG003
Part 2:Pembrolizumab 2 mg/kg+Dabrafenib 150 mg+Trametinib 2 mg
Participants with BRAF mutant melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG004
Part 2:Pembrolizumab 2 mg/kg+Trametinib 1.5 mg
Participants with BRAF wild-type melanoma received 2 mg/kg pembrolizumab administered by IV infusion on Days 1 and 22 Q6W and 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG005
Part 4:4 Weeks Trametinib (Tra) 2mg; Pembrolizumab+Tra 2mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 of each 3-week cycle (Q3W) and a concurrent dosing schedule of 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG006
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG007
Part 4:4 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 4 weeks. Starting with Week 5, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG008
Part 4:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
OG009
Part 4:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 1.5 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
OG010
Part 5:2 Weeks Tra 1.5mg; Pembrolizumab+Tra 1.5mg
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 1.5 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and a concurrent dosing schedule of 1.5 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
OG011
Part 5:2 Weeks Tra 2mg; Pembrolizumab+Tra 2mg Intermittent
Participants with BRAF wild-type melanoma or solid tumors (irrespective of BRAF status) received 2 mg trametinib orally QD for 2 weeks. Starting with Week 3, participants received 200 mg pembrolizumab administered by IV infusion on Day 1 Q3W and an intermittent dose schedule of 2 mg trametinib orally QD with 1 week OFF trametinib and 2 weeks ON trametinib continuing up until study treatment discontinuation.
Units
Counts
Participants
OG0007
OG0013
OG0022
OG0038
OG0042
OG0053
OG0064
OG0075
OG0086
OG0093
OG01012
OG0119
Title
Denominators
Categories
Title
Measurements
OG0002
OG0012
OG0021
OG0035
OG0042
OG0051
OG0060
OG0074
OG0082
OG0091
OG0102
OG0112
7
Title
Denominators
Categories
Title
Measurements
OG00057.1(18.4 to 90.1)
8
Title
Denominators
Categories
Title
Measurements
OG00075.0(34.9 to 96.8)
Units
Counts
Participants
OG00060
OG00160
Title
Denominators
Categories
Title
Measurements
OG00065.0(51.6 to 76.9)
OG00171.7(58.6 to 82.5)
Participants with BRAF mutant melanoma received saline placebo administered by IV infusion on Days 1 and 22 Q6W; 150 mg/day total dabrafenib orally, in a divided dose, BID starting on Day 1 and continuing up until study treatment discontinuation; and 2 mg trametinib orally QD starting on Day 1 and continuing up until study treatment discontinuation.
Units
Counts
Participants
OG00039
OG00143
Title
Denominators
Categories
Title
Measurements
OG00030.2(14.1 to NA)NA = Upper limit for DOR was not reached at time of data cut-off due to insufficient number of responding participants with relapse
OG00112.1(6.0 to 15.7)
Units
Counts
Participants
OG00060
OG00160
Title
Denominators
Categories
Title
Measurements
OG00046.3(23.9 to NA)NA = Upper limit for OS was not reached at time of data cut-off due to insufficient number of participants with an event