A Study of Cobimetinib Administered as Single Agent and i... | NCT03312530 | Trialant
NCT03312530
Sponsor
Hoffmann-La Roche
Status
Completed
Last Update Posted
Feb 28, 2023Actual
Enrollment
49Actual
Phase
Phase 1Phase 2
Conditions
Multiple Myeloma
Interventions
Cobimetinib
Venetoclax
Atezolizumab
Countries
Czechia
Denmark
France
Germany
Netherlands
Norway
Poland
Spain
Sweden
Protocol Section
Identification Module
NCT ID
NCT03312530
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
BO39813
Secondary IDs
ID
Type
Description
Link
2017-000830-68
EudraCT Number
Brief Title
A Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Participants With Relapsed and Refractory Multiple Myeloma
Official Title
A Phase Ib/II Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Patients With Relapsed and Refractory Multiple Myeloma
Acronym
Not provided
Organization
Hoffmann-La RocheINDUSTRY
Status Module
Record Verification Date
Feb 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 13, 2017Actual
Primary Completion Date
May 18, 2021Actual
Completion Date
May 18, 2021Actual
First Submitted Date
Oct 12, 2017
First Submission Date that Met QC Criteria
Oct 12, 2017
First Posted Date
Oct 17, 2017Actual
Results Waived
Not provided
Results First Submitted Date
May 11, 2022
Results First Submitted that Met QC Criteria
Feb 27, 2023
Results First Posted Date
Feb 28, 2023Actual
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
Feb 27, 2023
Last Update Posted Date
Feb 28, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Hoffmann-La RocheINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Not provided
Is FDA Regulated Drug
No
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 open-label, randomized, multicenter, triple-arm Phase Ib/II study is designed to assess the efficacy, safety, tolerability, and pharmacokinetics of cobimetinib administered as a single agent (Arm A), cobimetinib plus venetoclax (Arm B), and cobimetinib plus venetoclax plus atezolizumab (Arm C) in participants with relapsed and refractory multiple myeloma. Two successive cohorts will evaluate the safety of cobimetinib plus venetoclax and that of cobimetinib plus venetoclax plus atezolizumab in the selected population during the safety run-in phase of the study. Once the dose levels have demonstrated acceptable safety during this phase, randomization will begin for all treatment arms (Arms A, B, and C).
Detailed Description
Not provided
Conditions Module
Conditions
Multiple Myeloma
Keywords
Not provided
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
49Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
A: Cobimetinib
Experimental
Participants will receive the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants will be allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Cobimetinib
Drug: Atezolizumab
B: Cobimetinib + Venetoclax
Experimental
Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Cobimetinib
Drug: Venetoclax
C: Cobimetinib + Venetoclax + Atezolizumab
Experimental
Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Cobimetinib
Drug
Cobimetinib will be administered as per the schedule specified in the respective arm.
A: Cobimetinib
B: Cobimetinib + Venetoclax
C: Cobimetinib + Venetoclax + Atezolizumab
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An AE was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. New or pre-existing conditions which worsened during the study were also considered AEs.
Randomization up to end of study (up to approximately 3 years, 7 months)
Percentage of Participants With Overall Response Rate (ORR) as Determined by the Investigator Using International Myeloma Working Group (IMWG) Response Criteria
ORR was defined as a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) and was analyzed in the safety evaluable population and in the biomarker-selected sub-populations of t(11;14) and RAS mutations.
From randomization to the first occurrence of a response as defined above (up to approximately 3 years, 7 months)
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Participants With Clinical Benefit as Determined by the Investigator Using IMWG Response Criteria
Clinical benefit rate (CBR) was defined as a minimal response (MR) or better (PR,VGPR, CR, sCR).
From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 3 years, 7 months)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Life expectancy of at least 12 weeks
Documented multiple myeloma
Received 3 to 5 prior lines of therapy for multiple myeloma, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
Achieved a response (minimal response [MR] or better) to at least one prior regimen
Documented evidence of progressive disease (as defined by the IMWG criteria) on or after their last prior therapy, or participants who were intolerant to their last prior therapy
Toxicities resulting from previous therapy (including peripheral neuropathy) that must be resolved or stabilized to Grade 1
Exclusion Criteria:
Anti-myeloma treatment within 14 days or 5 pharmacokinetic (PK) half-lives of the treatment, whichever is longer, before the date of randomization
Completion of autologous stem cell transplant within 100 days prior to the date of randomization
Prior allogeneic stem cell transplant as well as prior solid organ transplant
Spinal cord compression not definitively treated with surgery and/or radiation
Prior treatment with MEK inhibitors, B-cell lymphoma-2 (Bcl-2) inhibitors, or immune checkpoint inhibitor therapies including anti-cytotoxic T-lymphocyte associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1)
Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
Treatment with systemic immunosuppressive medication within 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
Prior radiation therapy within 14 days prior to study enrollment and/or persistence of radiation-related adverse effects
History or evidence of retinal pathology on ophthalmic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
Left ventricular ejection fraction (LVEF) below institutional lower limit of normal
History of clinically significant cardiovascular dysfunction
Any previous venous thromboembolism greater than (>) Grade 3 within 12 months of study enrollment
History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins (for participants in Arm C only)
History of other malignancy that could affect compliance with the protocol or interpretation of results
Active or history of autoimmune disease or immune deficiency
History of malabsorption or other condition that would interfere with absorption of study drugs
Active tuberculosis
Severe infection within 28 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment
Positive test results for hepatitis B (hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [HBcAb]) or hepatitis C virus (HCV) antibody
Known history of human immunodeficiency virus (HIV) seropositivity
Treatment with a live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior to Cycle 1 Day 1, at any time during the study, and for at least 5 months after the last dose of study drug (for participants in Arm C only)
Received strong cytochrome P-3A (CYP3A) inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, and moderate CYP3A inducers within 7 days prior to the initiation of study treatment
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Clinical Trials
Hoffmann-La Roche
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Schjesvold F, Paiva B, Ribrag V, Rodriguez-Otero P, San-Miguel JF, Robak P, Hansson M, Onishi M, Hamidi H, Malhi V, Dail M, Javery A, Ku G, Raab MS. Cobimetinib Alone and Plus Venetoclax With/Without Atezolizumab in Patients With Relapsed/Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2023 Jan;23(1):e59-e70. doi: 10.1016/j.clml.2022.10.006. Epub 2022 Oct 22.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 62 participants were screened, of which a total of 49 participants were enrolled.
Recruitment Details
The study was conducted at 16 centers in 8 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants will receive cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants will receive cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
Progression-Free Survival (PFS) as Determined by the Investigator Using IMWG Response Criteria
PFS was defined as the time from randomization (for randomized participants) or first treatment date (for non-ranomized participants) to the first occurrence of disease progression or relapse as determined by the investigator using the IMWG criteria or death from any cause during the study, whichever occurred first.
From enrollment or first treatment date to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 3 years, 7 months)
Duration of Response (DOR) as Determined by the Investigator Using IMWG Response Criteria
DOR was applicable to participants who achieved at least a PR, and was measured from the first observation of PR or better to the time of disease progression.
Time from the first observation of partial response (PR) or better to the time of disease progression (up to approximately 3 years, 7 months)
Overall Survival (OS)
OS was defined as the time from randomization until death from any cause.
From randomization until death from any cause (up to approximately 3 years, 7 months)
Area Under the Plasma Concentration Versus Time Curve (AUC) of Cobimetinib
AUC0-24hr area under the plasma concentration-time curve from time 0 to 24 hrs
Pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
Maximum Observed Plasma Concentration (Cmax) of Cobimetinib
Cmax is the maximum observed plasma concentration at steady state.
Pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
Time to Reach Cmax (Tmax) of Cobimetinib
Tmax is the time to reach Cmax.
Pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
AUClast of Venetoclax
AUClast=area under the plasma concentration-time curve (samples collected to 8hr postdose on C1D15)
Pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
Cmax of Venetoclax
Cmax is the maximum observed plasma concentration at steady state.
Pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
Tmax of Venetoclax
Tmax is the time to reach Cmax.
Pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3 (cycle length: 28 days); at treatment discontinuation visit (up to approximately 3 years, 7 months)
Ostrava
708 52
Czechia
Univerzita Karlova v Praze a Vseobecna fakultni nemocnice v Praze - 1; Lekarska Fakulta - I
Prague
128 08
Czechia
Rigshospitalet; Hæmatologisk Klinik
København Ø
2100
Denmark
Odense Universitetshospital
Odense C
5000
Denmark
CHU - Hôtel Dieu hematolgie clinique
Nantes
44093
France
Hôpital Saint-Louis
Paris
75475
France
CHU Lyon - Centre Hospitalier Lyon Sud
Pierre-Benite (Lyon)
69495
France
IGR
Villejuif
94800
France
UNI-Klinikum Heidelberg Medizinische Klinik Innere Medizin V
Heidelberg
69120
Germany
Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik
Mainz
55131
Germany
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
Tübingen
72076
Germany
Universtitätsklinikum Ulm; Klinik für Innere Medizin III
Ulm
89081
Germany
Amsterdam UMC Location AMC
Amsterdam
1105 AZ
Netherlands
Universitair Medisch Centrum Utrecht
Utrecht
3584 CX
Netherlands
Førde sentralsjukehus
Førde
6800
Norway
Oslo University Hospital HF, Rikshospitalet
Oslo
0424
Norway
Medical University School; Dept. of Haematology
Lodz
93-510
Poland
Uniwersytet Medyczny im.Karola Marcinkowskiego w Poznaniu
Późna
60-569
Poland
Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
Warsaw
02-781
Poland
Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
Badalona
Barcelona
08915
Spain
ClÃnica Universidad de Navarra
Pamplona
Navarre
31620
Spain
Hospital Clinic de Barcelona
Barcelona
08036
Spain
Hospital Universitario de la Princesa
Madrid
28006
Spain
Hospital Univ 12 de Octubre
Madrid
28041
Spain
Skånes Universitetssjukhus
Lund
221 85
Sweden
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
FG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
FG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
FG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG00316 subjects
FG00415 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
NOT COMPLETED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG00316 subjects
FG00415 subjects
Type
Comment
Reasons
Death
FG0005 subjects
FG0015 subjects
FG0024 subjects
FG00310 subjects
FG0048 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Participant in another sponsor study.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Study terminated by sponsor
FG0001 subjects
FG0010 subjects
FG0022 subjects
FG0033 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Participant summarized as 'ongoing' due to missing data entry for Long-term Follow Up period on eCRF
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
BG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
BG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
BG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0026
BG00316
BG00415
BG00549
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
BG00065.8± 7.6
BG00166.5± 6.1
BG00268.0± 5.9
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0004
BG0013
BG002
Race/Ethnicity, Customized
Number
Participants
Title
Denominators
Categories
White
Title
Measurements
BG0006
BG0016
BG002
Race/Ethnicity, Customized
Number
Participants
Title
Denominators
Categories
Hispanic or Latino
Title
Measurements
BG0000
BG0010
BG002
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
Percentage of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An AE was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. New or pre-existing conditions which worsened during the study were also considered AEs.
The safety evaluable population included all participants who received any amount of study drug.
Posted
Number
Percentage of Participants
Randomization up to end of study (up to approximately 3 years, 7 months)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG000100.0
OG001100.0
OG002100.0
OG003
Primary
Percentage of Participants With Overall Response Rate (ORR) as Determined by the Investigator Using International Myeloma Working Group (IMWG) Response Criteria
ORR was defined as a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) and was analyzed in the safety evaluable population and in the biomarker-selected sub-populations of t(11;14) and RAS mutations.
The safety evaluable population included all participants who received any amount of study drug.
Posted
Number
95% Confidence Interval
Percentage of Participants
From randomization to the first occurrence of a response as defined above (up to approximately 3 years, 7 months)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Secondary
Percentage of Participants With Clinical Benefit as Determined by the Investigator Using IMWG Response Criteria
Clinical benefit rate (CBR) was defined as a minimal response (MR) or better (PR,VGPR, CR, sCR).
The safety evaluable population included all participants who received any amount of study drug.
Posted
Number
95% Confidence Interval
Percentage of Participants
From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 3 years, 7 months)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Progression-Free Survival (PFS) as Determined by the Investigator Using IMWG Response Criteria
PFS was defined as the time from randomization (for randomized participants) or first treatment date (for non-ranomized participants) to the first occurrence of disease progression or relapse as determined by the investigator using the IMWG criteria or death from any cause during the study, whichever occurred first.
The safety evaluable population included all participants who received any amount of study drug.
Posted
Median
95% Confidence Interval
Months
From enrollment or first treatment date to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 3 years, 7 months)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Secondary
Duration of Response (DOR) as Determined by the Investigator Using IMWG Response Criteria
DOR was applicable to participants who achieved at least a PR, and was measured from the first observation of PR or better to the time of disease progression.
The safety evaluable population included all participants who received any amount of study drug.
Posted
Median
95% Confidence Interval
Months
Time from the first observation of partial response (PR) or better to the time of disease progression (up to approximately 3 years, 7 months)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Overall Survival (OS)
OS was defined as the time from randomization until death from any cause.
The safety evaluable population included all participants who received any amount of study drug.
Posted
Median
95% Confidence Interval
Months
From randomization until death from any cause (up to approximately 3 years, 7 months)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of Cobimetinib
AUC0-24hr area under the plasma concentration-time curve from time 0 to 24 hrs
The PK population included participants from Arms A, B, and C who received at least one dose of study medication and for whom at least one evaluable PK sample was collected.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr*ng/mL
Pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Cobimetinib
Cmax is the maximum observed plasma concentration at steady state.
The PK population included participants from Arms A, B, and C who received at least one dose of study medication and for whom at least one evaluable PK sample was collected.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Time to Reach Cmax (Tmax) of Cobimetinib
Tmax is the time to reach Cmax.
The PK population included participants from Arms A, B, and C who received at least one dose of study medication and for whom at least one evaluable PK sample was collected.
Posted
Median
Full Range
hr
Pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
AUClast of Venetoclax
AUClast=area under the plasma concentration-time curve (samples collected to 8hr postdose on C1D15)
The PK population included participants from Arms B and C who received at least one dose of study medication and for whom at least one evaluable PK sample was collected.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr*ug/mL
Pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Cmax of Venetoclax
Cmax is the maximum observed plasma concentration at steady state.
The PK population included participants from Arms B and C who received at least one dose of study medication and for whom at least one evaluable PK sample was collected.
Posted
Geometric Mean
Geometric Coefficient of Variation
ug/mL
Pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Tmax of Venetoclax
Tmax is the time to reach Cmax.
The PK population included participants from Arms B and C who received at least one dose of study medication and for whom at least one evaluable PK sample was collected.
Posted
Median
Full Range
hr
Pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days)
ID
Title
Description
OG000
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG002
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Secondary
Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
The immunogenicity analysis population for atezolizumab consisted of all participants from Arm C with any ADA assessment.
Posted
Count of Participants
Participants
Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3 (cycle length: 28 days); at treatment discontinuation visit (up to approximately 3 years, 7 months)
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
OG001
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Time Frame
Randomization up to end of study (up to approximately 3 years, 7 months)
Description
AEs were recorded for the safety-evaluable population, which included all participants who received any amount of study drug and analyzed according to the treatment arm they received.
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
Safety Run-In: Cobimetinib + Venetoclax
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Participants received cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
5
6
3
6
6
6
EG002
A: Cobimetinib
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
4
6
3
6
5
6
EG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
11
16
12
16
15
16
EG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
8
15
11
15
15
15
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 affected6 at risk
EG0015 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG0032 events1 affected16 at risk
EG0040 events0 affected15 at risk
FEBRILE NEUTROPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NEUTROPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0013 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
THROMBOCYTOPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INTESTINAL ULCER
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
GENERAL PHYSICAL HEALTH DETERIORATION
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PAIN
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PYREXIA
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CHOLECYSTITIS
Hepatobiliary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
GASTROINTESTINAL INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMOPHILUS SEPSIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INFLUENZA
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INTERVERTEBRAL DISCITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
LISTERIA SEPSIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ORAL HERPES
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PNEUMOCOCCAL BACTERAEMIA
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PNEUMONIA
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PNEUMONIA PNEUMOCOCCAL
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
PROSTATE INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
STAPHYLOCOCCAL SEPSIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NEUTROPHIL COUNT DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RESPIROVIRUS TEST POSITIVE
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERCALCAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPOKALAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPONATRAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
TUMOUR LYSIS SYNDROME
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NECK PAIN
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMORRHAGIC STROKE
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
SPINAL CORD COMPRESSION
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SYNCOPE
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ACUTE KIDNEY INJURY
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RENAL FAILURE
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RESPIRATORY FAILURE
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 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 events1 affected6 at risk
EG0012 events2 affected6 at risk
EG0021 events1 affected6 at risk
EG00311 events9 affected16 at risk
EG00414 events9 affected15 at risk
FEBRILE NEUTROPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMORRHAGIC DIATHESIS
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
LEUKOPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0004 events2 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
LYMPHOPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NEUTROPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0004 events3 affected6 at risk
EG00110 events4 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PANCYTOPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
THROMBOCYTOPENIA
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ATRIOVENTRICULAR BLOCK
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CARDIAC FAILURE
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SUPRAVENTRICULAR TACHYCARDIA
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
TINNITUS
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
VERTIGO
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERPARATHYROIDISM
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERTHYROIDISM
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPOTHYROIDISM
Endocrine disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLEPHARITIS
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLEPHAROCHALASIS
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CHALAZION
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DETACHMENT OF RETINAL PIGMENT EPITHELIUM
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DRY EYE
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
EYE HAEMORRHAGE
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
OPTIC NERVE CUPPING
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PHOTOPHOBIA
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RETINAL HAEMORRHAGE
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
SUBRETINAL FLUID
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SWELLING OF EYELID
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
VISUAL IMPAIRMENT
Eye disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ABDOMINAL PAIN UPPER
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ANORECTAL DISCOMFORT
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CONSTIPATION
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0023 events1 affected6 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG00010 events5 affected6 at risk
EG0019 events6 affected6 at risk
EG0022 events2 affected6 at risk
EG003
DRY MOUTH
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DYSPEPSIA
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DYSPHAGIA
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FAECES DISCOLOURED
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FLATULENCE
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
GASTROINTESTINAL PAIN
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
GASTROOESOPHAGEAL REFLUX DISEASE
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMATEMESIS
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMORRHOIDS
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
MELAENA
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NAUSEA
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0007 events6 affected6 at risk
EG0014 events4 affected6 at risk
EG0021 events1 affected6 at risk
EG003
ORAL DISCOMFORT
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ORAL PAIN
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PROCTITIS
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
STOMATITIS
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ASTHENIA
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CHEST PAIN
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FACE OEDEMA
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FATIGUE
General disorders
MedDRA 24.0
Systematic Assessment
EG0005 events4 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FEELING COLD
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
GENERAL PHYSICAL HEALTH DETERIORATION
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
OEDEMA
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
OEDEMA PERIPHERAL
General disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected6 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
PAIN
General disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PYREXIA
General disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERSENSITIVITY
Immune system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BRONCHIOLITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BRONCHITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CANDIDA INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CELLULITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
CONJUNCTIVITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0013 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DEVICE RELATED INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
EAR INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HERPES SIMPLEX
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HERPES ZOSTER
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
IMPETIGO
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INFLUENZA
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NASOPHARYNGITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0013 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ORAL CANDIDIASIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ORAL HERPES
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
OTITIS EXTERNA
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
PNEUMONIA
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PNEUMONIA PNEUMOCOCCAL
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
RASH PUSTULAR
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
RESPIRATORY SYNCYTIAL VIRUS INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SALMONELLOSIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SINUSITIS
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SKIN INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0022 events1 affected6 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
WOUND INFECTION
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
EYE CONTUSION
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FALL
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ALANINE AMINOTRANSFERASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
AMYLASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ASPARTATE AMINOTRANSFERASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD ALKALINE PHOSPHATASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD BILIRUBIN INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD CALCIUM INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD CREATINE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD CREATINE PHOSPHOKINASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0003 events3 affected6 at risk
EG0013 events3 affected6 at risk
EG0021 events1 affected6 at risk
EG003
BLOOD CREATININE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD LACTATE DEHYDROGENASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD POTASSIUM DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0012 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
BLOOD URIC ACID INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
EJECTION FRACTION DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMOGLOBIN DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INFLUENZA A VIRUS TEST POSITIVE
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
LIPASE INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
LYMPHOCYTE COUNT DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NEUTROPHIL COUNT DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PLATELET COUNT DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
TROPONIN INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
TROPONIN T INCREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
VITAMIN B12 DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
WEIGHT DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
WHITE BLOOD CELL COUNT DECREASED
Investigations
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
FOLATE DEFICIENCY
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERKALAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERPHOSPHATAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERTRIGLYCERIDAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERURICAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPOCALCAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPOKALAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPOMAGNESAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPONATRAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPOPHOSPHATAEMIA
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ARTHRALGIA
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0022 events2 affected6 at risk
EG003
BONE PAIN
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
MUSCLE SPASMS
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
OSTEOARTHRITIS
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PAIN IN EXTREMITY
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
ADENOCARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
TUMOUR PAIN
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
AUTONOMIC NEUROPATHY
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DYSAESTHESIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DYSGEUSIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HEADACHE
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0003 events2 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERAESTHESIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HYPERSOMNIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
HYPOAESTHESIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NEURALGIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
NEUROPATHY PERIPHERAL
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PARAESTHESIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PERIPHERAL SENSORY NEUROPATHY
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
POST HERPETIC NEURALGIA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SCIATICA
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SYNCOPE
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
INSOMNIA
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
POLLAKIURIA
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
RENAL COLIC
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
RENAL FAILURE
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
URINARY INCONTINENCE
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
URINARY TRACT PAIN
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
BALANOPOSTHITIS
Reproductive system and breast disorders
MedDRA 24.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
EPISTAXIS
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
PRODUCTIVE COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SINUS PAIN
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ALOPECIA
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DERMATITIS
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DERMATITIS ACNEIFORM
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DRY SKIN
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ECCHYMOSIS
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ERYTHEMA
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
HYPERHIDROSIS
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
PRURITUS
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0003 events2 affected6 at risk
EG0010 events0 affected6 at risk
EG0023 events1 affected6 at risk
EG003
RASH
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0002 events2 affected6 at risk
EG0012 events2 affected6 at risk
EG0024 events3 affected6 at risk
EG003
RASH MACULO-PAPULAR
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SEBORRHOEA
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
SKIN ULCER
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0012 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
DEEP VEIN THROMBOSIS
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
ESSENTIAL HYPERTENSION
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
HAEMATOMA
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
HYPERTENSION
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
PERIPHERAL VENOUS DISEASE
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
In March 2019, this study was placed on voluntary enrollment hold. In May 2019, after an informal efficacy review, the Sponsor decided not to remove the hold and discontinued further development of the combination.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
OG00415
Title
Denominators
Categories
Safety Population
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG00316
ParticipantsOG00415
Title
Measurements
OG00016.7(0.00 to 54.82)
OG00133.3(0.00 to 79.39)
OG0020(0.0 to 8.33)
OG003
t(11;14) Population
ParticipantsOG0000
ParticipantsOG0011
ParticipantsOG0021
ParticipantsOG0032
RAS Mutation Population
ParticipantsOG0002
ParticipantsOG0011
ParticipantsOG0022
ParticipantsOG0037
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
OG00415
Title
Denominators
Categories
Title
Measurements
OG00033.3(0.00 to 79.39)
OG00133.3(0.00 to 79.39)
OG0020(0.00 to 8.33)
OG00343.8(16.32 to 71.18)
OG00433.3(6.14 to 60.52)
Participants received the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants were allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
OG00415
Title
Denominators
Categories
Title
Measurements
OG0001.7(0.9 to 3.7)
OG0013.4(2.1 to 4.6)
OG0022.8(1.9 to 4.7)
OG0034.9(1.9 to 10.3)
OG0043.8(1.4 to 4.7)
OG003
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0001
OG0012
OG0025
OG0034
Title
Denominators
Categories
Title
Measurements
OG00011.5(NA to NA)NA = not estimable, could not be calculated due to too few events.
OG0014.9(2.3 to NA)NA = not estimable, could not be calculated due to too few events.
OG00215.2(1.9 to NA)NA = not estimable, could not be calculated due to too few events.
OG003NA(1.9 to NA)NA = not estimable, could not be calculated due to too few events.
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG00316
OG00415
Title
Denominators
Categories
Title
Measurements
OG00011.4(6.3 to 13.9)
OG00114.3(14.1 to NA)NA = not estimable, could not be calculated due to too few events.
OG00212.9(3.2 to NA)NA = not estimable, could not be calculated due to too few events.
OG00313.5(8.0 to 26.9)
OG00422.0(15.5 to NA)NA = not estimable, could not be calculated due to too few events.
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0004
OG0014
OG0020
OG00311
OG0049
Title
Denominators
Categories
Title
Measurements
OG0002390± 53.4
OG0013190± 55.3
OG0032540± 78.1
OG0042900± 54.6
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0004
OG0015
OG0020
OG00313
OG00412
Title
Denominators
Categories
Title
Measurements
OG000157± 63.5
OG001192± 61.7
OG003148± 72.6
OG004166± 61.0
OG003
B: Cobimetinib + Venetoclax
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
OG004
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0004
OG0015
OG0020
OG00313
OG00412
Title
Denominators
Categories
Title
Measurements
OG0004.00(2.10 to 4.02)
OG0014.00(2.05 to 5.73)
OG0034.00(2.00 to 6.08)
OG0044.00(2.23 to 6.37)
OG003
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0004
OG0015
OG00213
OG00311
Title
Denominators
Categories
Title
Measurements
OG0004.96± 67.2
OG0015.13± 57.0
OG0026.52± 63.7
OG0036.52± 51.3
OG003
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.
Units
Counts
Participants
OG0004
OG0015
OG00213
OG00311
Title
Denominators
Categories
Title
Measurements
OG0001.25± 81.0
OG0011.16± 48.7
OG0021.32± 55.3
OG0031.35± 18.2
OG003
C: Cobimetinib + Venetoclax + Atezolizumab
Participants received cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurred first.