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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002794-35 | EudraCT Number |
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Sponsor decision
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The purpose of this study was to evaluate safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in patients with BRAF V600 mutant, unresectable and metastatic melanoma.
This study was designed as a phase III, multi-center study consisting of 3 parts:
For all parts of the study, the treatment continued until the subject experiences any of the following events: disease progression according to RECIST 1.1 as determined by the Investigator, unacceptable toxicity, initiation of a new anti-neoplastic therapy, pregnancy, withdrawal of consent, physician's decision, loss to follow-up, death, or termination of the study by the Sponsor. Safety evaluations are conducted for all subjects for up to 150 days after the last dose of spartalizumab/placebo (safety follow-up period).
Subjects who discontinued study treatment without disease progression as per RECIST 1.1 continued with tumor assessments according to the protocol until documented disease progression, withdrawal of consent, loss to follow-up, or death, regardless of the initiation of new anti-neoplastic therapy (efficacy follow-up period).
Subjects entered the survival follow-up period after completing the safety follow-up period or experiencing disease progression as per RECIST 1.1 or response criteria for immunotherapy, whichever period is longer (survival follow-up period).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Safety run-in Cohort | Experimental | In Part 1, participants are treated at different dose levels to determine the recommended Phase 3 regimen of spartalizumab in combination with dabrafenib and trametinib. The starting dose of spartalizumab is 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD). |
|
| Part 2: Biomarker cohort | Experimental | In Part 2, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD). |
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| Part 3- Arm 1: Spartalizumab in combination with dabrafenib and trametinib | Experimental | In Part 3, participants are randomized to receive spartalizumab at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
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| Part 3- Arm 2: Placebo in combination with dabrafenib and trametinib | Placebo Comparator | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Spartalizumab | Biological | Spartalizumab powder for solution is used in Part 1 and Part 2, and as concentrate for solution for infusion for Part 3. Spartalizumab is administered via intravenous infusion over 30 minutes once every 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs) | DLT was defined as an adverse event or abnormal laboratory value that was unrelated to disease, disease progression, inter-current illness, or concomitant medications and occured within 8 weeks of treatment with spartalizumab in combination with dabrafenib and trametinib. The DLT criteria included Grade 4 hematological adverse events, Grade 4 bilirubin elevation, specific gastrointestinal adverse events, symptomatic serum amylase or lipase elevation, Grade 3 or higher hypertension, Grade 3 or higher cardiac events, Grade 2 or higher pneumonitis, Grade 3 or higher immune-related toxicities, infusion-related reactions, other clinically significant adverse events, and toxicities leading to a dosing delay of over 12 weeks. NCI CTCAE v4.03 was used for grading DLTs | Up to 8 weeks (Part 1) |
| Biomarker Cohort (Part 2): Change From Baseline in Programmed Cell Death-ligand 1 (PD-L1) Expression Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib | Change from baseline in PD-L1 expression (as determined by immunohistochemistry in tissue samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2 | Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days |
| Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib | Change from baseline in CD8+ cells (as determined by flow cytometry in blood samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2 | Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days |
| Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1 | Progression-free survival was defined as the time from the date of first dose to the date of the first documented radiological progression per investigator's assessment according to RECIST 1.1 or death due to any cause. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | Overall survival was defined as the time from date of randomization to date of death due to any cause | Up to death due to any cause, assessed up to approximately 7 years |
| Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1 |
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Inclusion criteria Part 1: Safety run-in
Part 2: Biomarker cohort
Part 3: Double-blind, randomized, placebo-controlled part
Exclusion Criteria:
Part 1: Safety run-in
Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part
Other protocol-defined Inclusion/Exclusion may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Cancer Associates for Research and Excellence | Encinitas | California | 92024 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35728875 | Derived | Tawbi HA, Robert C, Brase JC, Gusenleitner D, Gasal E, Garrett J, Savchenko A, Gorgun G, Flaherty KT, Ribas A, Dummer R, Schadendorf D, Long GV, Nathan PD, Ascierto PA. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with BRAF V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i). J Immunother Cancer. 2022 Jun;10(6):e004226. doi: 10.1136/jitc-2021-004226. | |
| 35030011 |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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The screening phase began once written informed consent was provided and ended after 28 days or when subject received the first dose (Part 1 and 2) or was randomized (Part 3), whichever came first.
Part 1 and 2 were conducted in 18 centers across 12 countries. Part 3 is conducted in 190 centers across 29 countries
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 1, participants are treated with Spartalizumab (PDR001) 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD). |
| FG001 | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 27, 2023 | Jun 23, 2023 |
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Part 1 and Part 2 are open- label. Part 3 is double-blind and randomized.
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| Placebo | Other | Placebo is administered via intravenous infusion over 30 minutes once every 4 weeks |
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| Dabrafenib | Drug | Dabrafenib 150 mg capsules BID is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions. |
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| Trametinib | Drug | Trametinib 2 mg tablets QD is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions |
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| Up to disease progression or death due to any cause, whichever occurs first, assessed up to 2.8 years (Part 3) |
ORR was defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters |
| Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 years |
| Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1 | DOR was defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria. The distribution of DOR was estimated using the KM method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters | From first documented response to date of first documented progression or death, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3) |
| Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1 | DCR was defined as the percentage of participants with CR or PR or subjects with stable disease (SD) lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. | Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 year |
| Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status Scores | The EORTC QLQ-C30 was a 30-item questionnaire that patients complete, consisting of both multi-item scales and single-item measures. It included five functional scales, three symptom scales, six single items, and a Global Health Status/Quality of Life (GHS/QoL) scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The change from baseline in GHS/QoL scores was calculated. A positive change from baseline indicated improvement in the patient's quality of life. | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
| Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Physical Functioning Scale Scores | The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 physical functioning scale measured a patient's ability to carry out daily activities and tasks requiring physical exertion. It consisted of five questions asking patients to rate their level of physical functioning, with response options ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating better physical functioning. The change from baseline in physical functioning scale scores was calculated. A positive change from baseline indicated improvement in physical functioning. | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
| Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Pain Symptom Scale Scores | The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 pain symptom scale was one of the symptom scales in the questionnaire, which measured the severity of pain experienced by the patient. The pain symptom scale consisted of two items, one measuring the severity of pain and the other measuring the use of painkillers. The items were rated on a 4-point scale ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating more severe pain. The change from baseline in pain symptom scale scores was calculated. A negative change from baseline indicated improvement. | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
| Randomized (Part 3): Time to 10 Point Definitive Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status | The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The time to definitive 10 point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the GHS/QoL score or death due to any cause. If a subject had not had an event, the time to deterioration was censored at the date of the last adequate assessment. The distribution was estimated using KM method. | From baseline to date of at least 10 points relative to baseline worsening of the global health status score or death due to any cause, up to 2.8 years (Part 3) |
| Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score | The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) quality of life questionnaire was composed of the FACT-General (FACT-G) plus the Melanoma Subscale and the Melanoma Surgery Subscale, which complemented the general scale with items specific to quality of life (QoL) in melanoma. The Melanoma Subscale of FACT-M included 16 questions, with response options of 0= "Not at all", 1= "a little bit", 2= "somewhat", 3= "quite a bit" and 4= "very much". The FACT-M melanoma subscale score ranged from 0 to 64, with higher scores indicating a higher quality of life in relation to melanoma. The change from baseline in melanoma subscale scores was calculated. A positive change from baseline indicated improvement. | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
| Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score | The EQ-5D-5L is a standardized questionnaire used to assess health-related quality of life, and it includes a Visual Analog Scale (VAS). The VAS score is obtained by asking the individual to rate their current health status on a scale from 0 to 100, where 0 represents the worst possible health state and 100 represents the best possible health state. The change from baseline in EQ-5D-5L VAS score was calculated. A positive change from baseline indicates improvement in the health status. | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
| Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression | PFS was defined as the time from the date of first dose to the date of the first documented radiological progression as per investigator's assessment using RECIST 1.1 response criteria or death due to any cause. The distribution of PFS was estimated using the KM method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. PFS analysis was performed by PD-L1 status (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression. | Up to disease progression or death due to any cause, up to 2.8 years (Part 3) |
| Randomized (Part 3): OS by PD-L1 Expression | Overall survival was defined as the time from date of randomization to date of death due to any cause. OS analysis was performed by PD-L1 subgroup (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression. | Up to death due to any cause, assessed up to approximately 7 years |
| Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline | Spartalizumab ADA prevalence at baseline was calculated as the percentage of participants who had an spartalizumab ADA positive result at baseline. | Baseline |
| Spartalizumab ADA Incidence | Spartalizumab ADA incidence was calculated as the percentage of participants who were treatment-induced spartalizumab ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted spartalizumab ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer) | Throughout study until 150 days after the last dose of spartalizumab, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). |
| Trough Concentration (Ctrough) for Spartalizumab | Ctrough for spartalizumab refers to the serum concentration of spartalizumab immediately prior to the administration of a dose of spartalizumab on Day 1 of Cycle 2 and later cycles. | Pre-infusion on Day 1 of each Cycle starting from Cycle 2, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days |
| Pre-dose Plasma Concentration for Dabrafenib | Plasma concentration of dabrafenib immediately prior to the administration of a dose of dabrafenib. | Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days |
| Pre-dose Plasma Concentration for Trametinib | Plasma concentration of trametinib immediately prior to the administration of a dose of trametinib. | Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days |
| Number of Participants With Dose Interruptions | Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib | From baseline to end of treatment, assessed up to approximately 7 years |
| Number of Participants With Dose Reductions | Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib | From baseline to end of treatment, assessed up to approximately 7 years |
| Relative Dose Intensity | Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio (expressed as percentage) of dose intensity and planned dose intensity:
| From baseline to end of treatment, assessed up to approximately 7 years |
| UC Irvine Medical Center |
| Orange |
| California |
| 92613-4091 |
| United States |
| California Pacific Medical Center | San Francisco | California | 94115 | United States |
| Stanford Cancer Center | Stanford | California | 94305 | United States |
| University of Kansas Cancer Center | Westwood | Kansas | 66205 | United States |
| Johns Hopkins U | Lutherville | Maryland | 21093 | United States |
| Nebraska Cancer Specialists | Omaha | Nebraska | 68130 | United States |
| NYU Laura and Isaac Perlmutter Cancer Center | New York | New York | 10016 | United States |
| University of Pittsburgh Med Center | Pittsburgh | Pennsylvania | 15213 | United States |
| University of Tennessee Medical Ctr | Knoxville | Tennessee | 37920 | United States |
| Univ of TX MD Anderson Cancer Cntr | Houston | Texas | 77030 | United States |
| Utah Cancer Specialists | Salt Lake City | Utah | 84106 | United States |
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| Novartis Investigative Site | Omsk | 644013 | Russia |
| Novartis Investigative Site | Saint Petersburg | 197758 | Russia |
| Novartis Investigative Site | Saint Petersburg | 198255 | Russia |
| Novartis Investigative Site | Samara | 443011 | Russia |
| Novartis Investigative Site | Málaga | Andalusia | 29010 | Spain |
| Novartis Investigative Site | Seville | Andalusia | 41009 | Spain |
| Novartis Investigative Site | Jerez de la Frontera | Cadiz | 11407 | Spain |
| Novartis Investigative Site | Badalona | Catalonia | 08916 | Spain |
| Novartis Investigative Site | Barcelona | Catalonia | 08036 | Spain |
| Novartis Investigative Site | A Coruña | Galicia | 15006 | Spain |
| Novartis Investigative Site | Oviedo | Principality of Asturias | 33011 | Spain |
| Novartis Investigative Site | Valencia | Valencia | 46014 | Spain |
| Novartis Investigative Site | Las Palmas de Gran Canaria | 35016 | Spain |
| Novartis Investigative Site | Madrid | 28009 | Spain |
| Novartis Investigative Site | Madrid | 28034 | Spain |
| Novartis Investigative Site | Madrid | 28050 | Spain |
| Novartis Investigative Site | Madrid | 28222 | Spain |
| Novartis Investigative Site | Gothenburg | SE-413 45 | Sweden |
| Novartis Investigative Site | Lund | 221 85 | Sweden |
| Novartis Investigative Site | Stockholm | SE 171 76 | Sweden |
| Novartis Investigative Site | Aarau | Canton of Aargau | 5001 | Switzerland |
| Novartis Investigative Site | Zurich | 8091 | Switzerland |
| Novartis Investigative Site | Songkhla | Hat Yai | 90110 | Thailand |
| Novartis Investigative Site | Bangkok | 10330 | Thailand |
| Novartis Investigative Site | Truro | Cornwall | TR1 3LJ | United Kingdom |
| Novartis Investigative Site | Guildford | Surrey | GU2 7XX | United Kingdom |
| Novartis Investigative Site | Sutton | Surrey | SM2 5PT | United Kingdom |
| Novartis Investigative Site | Leicester | LE1 5WW | United Kingdom |
| Novartis Investigative Site | London | NW3 2QG | United Kingdom |
| Novartis Investigative Site | Manchester | M20 2BX | United Kingdom |
| Novartis Investigative Site | Middlesbrough | TS4 3BW | United Kingdom |
| Novartis Investigative Site | Preston | PR2 9HT | United Kingdom |
| Novartis Investigative Site | Rickmansworth Road | WD187HT | United Kingdom |
| Derived |
| Dummer R, Long GV, Robert C, Tawbi HA, Flaherty KT, Ascierto PA, Nathan PD, Rutkowski P, Leonov O, Dutriaux C, Mandala M, Lorigan P, Ferrucci PF, Grob JJ, Meyer N, Gogas H, Stroyakovskiy D, Arance A, Brase JC, Green S, Haas T, Masood A, Gasal E, Ribas A, Schadendorf D. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022 May 1;40(13):1428-1438. doi: 10.1200/JCO.21.01601. Epub 2022 Jan 14. |
| 33020648 | Derived | Dummer R, Lebbe C, Atkinson V, Mandala M, Nathan PD, Arance A, Richtig E, Yamazaki N, Robert C, Schadendorf D, Tawbi HA, Ascierto PA, Ribas A, Flaherty KT, Pakhle N, Campbell CD, Gusenleitner D, Masood A, Brase JC, Gasal E, Long GV. Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i. Nat Med. 2020 Oct;26(10):1557-1563. doi: 10.1038/s41591-020-1082-2. Epub 2020 Oct 5. |
In Part 2, participants are treated with Spartalizumab (PDR001) 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD). |
| FG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| FG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 1, participants are treated with Spartalizumab (PDR001) 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD). |
| BG001 | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 2, participants are treated with Spartalizumab (PDR001) 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD). |
| BG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| BG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs) | DLT was defined as an adverse event or abnormal laboratory value that was unrelated to disease, disease progression, inter-current illness, or concomitant medications and occured within 8 weeks of treatment with spartalizumab in combination with dabrafenib and trametinib. The DLT criteria included Grade 4 hematological adverse events, Grade 4 bilirubin elevation, specific gastrointestinal adverse events, symptomatic serum amylase or lipase elevation, Grade 3 or higher hypertension, Grade 3 or higher cardiac events, Grade 2 or higher pneumonitis, Grade 3 or higher immune-related toxicities, infusion-related reactions, other clinically significant adverse events, and toxicities leading to a dosing delay of over 12 weeks. NCI CTCAE v4.03 was used for grading DLTs | Dose-Determining Set (DDS) including all subjects in Part 1 who received at least one dose of study treatment who either 1) met the minimum exposure criterion and had sufficient safety evaluations, or 2) experienced a DLT during the first 8 weeks (56 days) of spartalizumab in combination with dabrafenib and trametinib dosing. | Posted | Count of Participants | Participants | Up to 8 weeks (Part 1) |
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| Primary | Biomarker Cohort (Part 2): Change From Baseline in Programmed Cell Death-ligand 1 (PD-L1) Expression Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib | Change from baseline in PD-L1 expression (as determined by immunohistochemistry in tissue samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2 | Participants in Part 2 who received at least one dose of study treatment and with evaluable data at the pre-specified time points | Posted | Mean | Standard Deviation | Percentage of positive tumor cells | Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days |
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| Primary | Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib | Change from baseline in CD8+ cells (as determined by flow cytometry in blood samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2 | Participants in Part 2 who received at least one dose of study treatment and with evaluable data at the pre-specified time points | Posted | Mean | Standard Deviation | Percentage Marker Area | Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days |
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| Primary | Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1 | Progression-free survival was defined as the time from the date of first dose to the date of the first documented radiological progression per investigator's assessment according to RECIST 1.1 or death due to any cause. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. | All participants in Part 3 to whom study treatment was assigned by randomization regardless of whether or not treatment was administered. | Posted | Median | 95% Confidence Interval | Months | Up to disease progression or death due to any cause, whichever occurs first, assessed up to 2.8 years (Part 3) |
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| Secondary | Overall Survival (OS) | Overall survival was defined as the time from date of randomization to date of death due to any cause | All participants to whom study treatment was assigned by randomization regardless of whether or not treatment was administered. | Posted | Median | 95% Confidence Interval | Months | Up to death due to any cause, assessed up to approximately 7 years |
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| Secondary | Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1 | ORR was defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters | For Part 1 and 2: all subjects to whom study treatment was assigned and who received at least one dose of any study treatment. For Part 3: all subjects to whom study treatment was assigned by randomization, regardless of whether or not treatment was administered. | Posted | Number | 95% Confidence Interval | Percentage of participants | Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 years |
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| Secondary | Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1 | DOR was defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria. The distribution of DOR was estimated using the KM method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters | For Part 1 and 2: all subjects to whom study treatment was assigned and who received at least one dose of any study treatment for whom best overall response was CR or PR. For Part 3: all subjects to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) for whom best overall response was CR or PR. | Posted | Median | 95% Confidence Interval | Months | From first documented response to date of first documented progression or death, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3) |
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| Secondary | Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1 | DCR was defined as the percentage of participants with CR or PR or subjects with stable disease (SD) lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. | For Part 1 and 2: all subjects to whom study treatment was assigned and who received at least one dose of any study treatment. For Part 3: all subjects to whom study treatment was assigned by randomization, regardless of whether or not treatment was administered. | Posted | Number | 95% Confidence Interval | Percentage of participants | Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 year |
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| Secondary | Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status Scores | The EORTC QLQ-C30 was a 30-item questionnaire that patients complete, consisting of both multi-item scales and single-item measures. It included five functional scales, three symptom scales, six single items, and a Global Health Status/Quality of Life (GHS/QoL) scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The change from baseline in GHS/QoL scores was calculated. A positive change from baseline indicated improvement in the patient's quality of life. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) and with available data at the pre-specified time points | Posted | Mean | Standard Deviation | Score on a Scale | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Physical Functioning Scale Scores | The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 physical functioning scale measured a patient's ability to carry out daily activities and tasks requiring physical exertion. It consisted of five questions asking patients to rate their level of physical functioning, with response options ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating better physical functioning. The change from baseline in physical functioning scale scores was calculated. A positive change from baseline indicated improvement in physical functioning. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) and with available data at the pre-specified time points | Posted | Mean | Standard Deviation | Score on a Scale | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Pain Symptom Scale Scores | The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 pain symptom scale was one of the symptom scales in the questionnaire, which measured the severity of pain experienced by the patient. The pain symptom scale consisted of two items, one measuring the severity of pain and the other measuring the use of painkillers. The items were rated on a 4-point scale ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating more severe pain. The change from baseline in pain symptom scale scores was calculated. A negative change from baseline indicated improvement. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) and with available data at the pre-specified time points | Posted | Mean | Standard Deviation | Score on a Scale | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): Time to 10 Point Definitive Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status | The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The time to definitive 10 point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the GHS/QoL score or death due to any cause. If a subject had not had an event, the time to deterioration was censored at the date of the last adequate assessment. The distribution was estimated using KM method. | All participants in Part 3 to whom study treatment was assigned by randomization regardless of whether or not treatment was administered. | Posted | Median | 95% Confidence Interval | Months | From baseline to date of at least 10 points relative to baseline worsening of the global health status score or death due to any cause, up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score | The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) quality of life questionnaire was composed of the FACT-General (FACT-G) plus the Melanoma Subscale and the Melanoma Surgery Subscale, which complemented the general scale with items specific to quality of life (QoL) in melanoma. The Melanoma Subscale of FACT-M included 16 questions, with response options of 0= "Not at all", 1= "a little bit", 2= "somewhat", 3= "quite a bit" and 4= "very much". The FACT-M melanoma subscale score ranged from 0 to 64, with higher scores indicating a higher quality of life in relation to melanoma. The change from baseline in melanoma subscale scores was calculated. A positive change from baseline indicated improvement. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) and with available data at the pre-specified time points | Posted | Mean | Standard Deviation | Score on a scale | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score | The EQ-5D-5L is a standardized questionnaire used to assess health-related quality of life, and it includes a Visual Analog Scale (VAS). The VAS score is obtained by asking the individual to rate their current health status on a scale from 0 to 100, where 0 represents the worst possible health state and 100 represents the best possible health state. The change from baseline in EQ-5D-5L VAS score was calculated. A positive change from baseline indicates improvement in the health status. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) and with available data at the pre-specified time points | Posted | Mean | Standard Deviation | Score on a Scale | From baseline to 60 days post progression, assessed up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression | PFS was defined as the time from the date of first dose to the date of the first documented radiological progression as per investigator's assessment using RECIST 1.1 response criteria or death due to any cause. The distribution of PFS was estimated using the KM method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. PFS analysis was performed by PD-L1 status (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) with an evaluable PD-L1 assessment. | Posted | Median | 95% Confidence Interval | Months | Up to disease progression or death due to any cause, up to 2.8 years (Part 3) |
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| Secondary | Randomized (Part 3): OS by PD-L1 Expression | Overall survival was defined as the time from date of randomization to date of death due to any cause. OS analysis was performed by PD-L1 subgroup (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression. | All participants in Part 3 to whom study treatment was assigned by randomization (regardless of whether or not treatment was administered) with an evaluable PD-L1 assessment. | Posted | Median | 95% Confidence Interval | Months | Up to death due to any cause, assessed up to approximately 7 years |
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| Secondary | Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline | Spartalizumab ADA prevalence at baseline was calculated as the percentage of participants who had an spartalizumab ADA positive result at baseline. | Part 1 and 2: All subjects to whom study treatment was assigned and who received any study treatment with a determinant baseline immunogenicity sample and at least one determinant post-baseline immunogenicity sample. Part 3: All subjects randomized to spartalizumab with dabrafenib and trametinib with a determinant baseline immunogenicity sample and at least one determinant post-baseline immunogenicity sample. Determinant sample: sample that is neither ADA-inconclusive nor unevaluable | Posted | Count of Participants | Participants | Baseline |
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| Secondary | Spartalizumab ADA Incidence | Spartalizumab ADA incidence was calculated as the percentage of participants who were treatment-induced spartalizumab ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted spartalizumab ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer) | Part 1 and 2: All subjects to whom study treatment was assigned and who received any study treatment with a determinant baseline immunogenicity sample and at least one determinant post-baseline immunogenicity sample. Part 3: All subjects randomized to spartalizumab with dabrafenib and trametinib with a determinant baseline immunogenicity sample and at least one determinant post-baseline immunogenicity sample. Determinant sample: sample that is neither ADA-inconclusive nor unevaluable | Posted | Count of Participants | Participants | Throughout study until 150 days after the last dose of spartalizumab, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). |
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| Secondary | Trough Concentration (Ctrough) for Spartalizumab | Ctrough for spartalizumab refers to the serum concentration of spartalizumab immediately prior to the administration of a dose of spartalizumab on Day 1 of Cycle 2 and later cycles. | All subjects who provided at least one evaluable spartalizumab PK concentration at the specified time points. | Posted | Mean | Standard Deviation | microgram (μg)/miliLiter (mL) | Pre-infusion on Day 1 of each Cycle starting from Cycle 2, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days |
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| Secondary | Pre-dose Plasma Concentration for Dabrafenib | Plasma concentration of dabrafenib immediately prior to the administration of a dose of dabrafenib. | All subjects who provided at least one evaluable dabrafenib PK concentration at the specified time points. | Posted | Mean | Standard Deviation | nanogram (ng)/ miliLiter (mL) | Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days |
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| Secondary | Pre-dose Plasma Concentration for Trametinib | Plasma concentration of trametinib immediately prior to the administration of a dose of trametinib. | All subjects who provided at least one evaluable trametinib PK concentration at the specified time points. | Posted | Mean | Standard Deviation | ng/mL | Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days |
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| Secondary | Number of Participants With Dose Interruptions | Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib | All participants who received at least one dose of study treatment | Posted | Count of Participants | Participants | From baseline to end of treatment, assessed up to approximately 7 years |
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| Secondary | Number of Participants With Dose Reductions | Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib | All participants who received at least one dose of study treatment | Posted | Count of Participants | Participants | From baseline to end of treatment, assessed up to approximately 7 years |
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| Secondary | Relative Dose Intensity | Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio (expressed as percentage) of dose intensity and planned dose intensity:
| All participants who received at least one dose of study treatment | Posted | Mean | Standard Deviation | Percentage of planned dose intensity | From baseline to end of treatment, assessed up to approximately 7 years |
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Adverse Events (AEs) were collected from first dose of study medication until the last dose plus 30 days safety follow-up, assessed up to approximately 86 months. Deaths were recorded from study start date until end of extended follow-up phase (end of study), assessed up to approximately 90 months.
Deaths in the extended follow-up (efficacy follow-up period or survival follow-up period) were not considered adverse events. The total number at risk in the extended follow-up included patients who entered this period. All-cause Mortality was assessed for all participants enrolled in the study, while Serious and Other Adverse Events were assessed for all participants who received at least one dose of the study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 1- Safety run-in: PDR001 400 mg Q4W + dabrafenib 150 mg BID + trametinib 2 mg QD - Events up to 30 days safety follow-up | 2 | 9 | 7 | 9 | 9 | 9 |
| EG001 | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker cohort: PDR001 400 mg Q4W + dabrafenib 150 mg BID + trametinib 2 mg QD - Events up to 30 days safety follow-up | 3 | 27 | 18 | 27 | 27 | 27 |
| EG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + dabrafenib 150 mg BID + trametinib 2 mg QD - Events up to 30 days safety follow-up | 28 | 267 | 150 | 267 | 262 | 267 |
| EG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + dabrafenib 150 mg BID + trametinib 2 mg QD - Events up to 30 days safety follow-up | 33 | 265 | 123 | 264 | 250 | 264 |
| EG004 | Part 1- Safety run-in: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 1- Safety run-in: Spartalizumab (PDR001) 400 mg Q4W + dabrafenib 150 mg BID + trametinib 2 mg QD (Extended F/Up) - Deaths in the extended follow-up (efficacy follow-up period or survival follow-up period) were not considered adverse events. | 1 | 7 | 0 | 0 | 0 | 0 |
| EG005 | Part 2- Biomarker Cohort: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD(Extended F/Up) | Part 2- Biomarker cohort: Spartalizumab (PDR001) 400 mg Q4W + dabrafenib 150 mg BID + trametinib 2 mg QD (Extended F/Up) - Deaths in the extended follow-up (efficacy follow-up period or survival follow-up period) were not considered adverse events. | 15 | 24 | 0 | 0 | 0 | 0 |
| EG006 | Part 3- Arm 1: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 3- Arm 1: Spartalizumab (PDR001) 400 mg Q4W + dabrafenib 150 mg BID + trametinib 2 mg QD (Extended F/Up) - Deaths in the extended follow-up (efficacy follow-up period or survival follow-up period) were not considered adverse events. | 99 | 239 | 0 | 0 | 0 | 0 |
| EG007 | Part 3- Arm 2: Placebo+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 3- Arm 2: Placebo + dabrafenib 150 mg BID + trametinib 2 mg QD (Extended F/Up) - Deaths in the extended follow-up (efficacy follow-up period or survival follow-up period) were not considered adverse events. | 117 | 232 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lymphadenopathy mediastinal | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Arteriosclerosis coronary artery | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cardiac disorder | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Coronary artery stenosis | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sinus node dysfunction | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypophysitis | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Angle closure glaucoma | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Detachment of retinal pigment epithelium | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Iridocyclitis | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Macular detachment | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Retinal degeneration | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal wall haematoma | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Autoimmune colitis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Umbilical hernia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Administration site extravasation | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Discomfort | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatotoxicity | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Liver disorder | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Contrast media allergy | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Haemophagocytic lymphohistiocytosis | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sarcoidosis | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Appendicitis perforated | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Bacterial food poisoning | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Febrile infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Post procedural infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Post procedural sepsis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Sweating fever | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Systemic infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary tract infection fungal | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Post embolisation syndrome | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Scapula fracture | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Wound haemorrhage | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Alanine aminotransferase abnormal | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Aspartate aminotransferase abnormal | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| General physical condition abnormal | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Streptococcus test positive | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sacral pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Soft tissue necrosis | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Adenocarcinoma pancreas | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Benign breast neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Malignant melanoma in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Non-Hodgkin's lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Oncologic complication | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Thyroid neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary tract neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Uterine neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cerebral haematoma | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Immune-mediated encephalopathy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Intracranial tumour haemorrhage | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Meningism | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Metabolic encephalopathy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Monoparesis | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nerve compression | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Neuritis | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Neurological decompensation | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Calculus urinary | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Immune-mediated nephritis | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nephritis | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Urethral stenosis | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Prostatic disorder | Reproductive system and breast disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Autoimmune lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Respiratory arrest | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dermatitis exfoliative generalised | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Toxic skin eruption | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Aneurysm ruptured | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypovolaemic shock | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Shock haemorrhagic | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ear congestion | Ear and labyrinth disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Motion sickness | Ear and labyrinth disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypophysitis | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Thyroiditis | Endocrine disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Iridocyclitis | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Myopia | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ocular discomfort | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Papilloedema | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Retinal haemorrhage | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vitreal cells | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cheilitis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Glossitis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Trichoglossia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Axillary pain | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Oedema due to cardiac disease | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Xerosis | General disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatic cytolysis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatic steatosis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sarcoidosis | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Gastrointestinal viral infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Otitis media chronic | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Viral pharyngitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Viral rhinitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Compression fracture | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood testosterone decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood thyroid stimulating hormone decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Globulins increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Myoglobin blood increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Fibrous histiocytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Anosmia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Peroneal nerve palsy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Bradyphrenia | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Nocturia | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Granuloma annulare | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Palmoplantar keratoderma | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Panniculitis | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sensitive skin | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Stasis dermatitis | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Superficial vein thrombosis | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862 778 8300 | Novartis.email@Novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 21, 2024 | May 28, 2025 | SAP_002.pdf |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D012878 | Skin Neoplasms |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000711728 | spartalizumab |
| C561627 | dabrafenib |
| C560077 | trametinib |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Other |
|
| Unknown |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
In Part 2, participants are treated with Spartalizumab (PDR001) 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
| OG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
In Part 2, participants are treated with Spartalizumab (PDR001) 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
| OG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG001 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG001 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG001 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
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In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
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| Participants |
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| Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
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| OG002 | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
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| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
|
|
In Part 3, participants are randomized to receive Spartalizumab (PDR001) at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)
| OG003 | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD) |
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| With at least one dose interruption |
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| With at least one dose interruption |
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| With at least one dose reduction and/or interruption |
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