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This open-label, dose-escalation study of vemurafenib in combination with cobimetinib will evaluate the safety, tolerability and pharmacokinetics in participants with BRAFV600 mutation-positive metastatic melanoma. Participants with previously untreated, BRAFV600E mutation-positive, locally advanced/unresectable or metastatic melanoma or those who have progressed on vemurafenib monotherapy immediately prior to enrolling in this trial are eligible. Participants will be assigned to different cohorts with escalating oral doses of vemurafenib and cobimetinib. This study consists of 2 stages, Stage 1 (Dose Escalation Stage [DES] and Cohort Expansion Stage [CES]) and the anticipated time on study treatment is until disease progression, unacceptable toxicity or any other discontinuation criterion is met.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib | Experimental | Participants will receive oral 60 milligrams (mg) cobimetinib once daily (QD) on Days 1-14, followed by 14 days off on Days 15-28 (14/14 dosing schedule) and oral 720 mg vemurafenib twice daily (BID) on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
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| DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on Days 1-21, followed by 7 days off on Days 22-28 (21/7 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
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| DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
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| DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on Days 1-28 (28/0 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cobimetinib | Drug | Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) During DES in Combination Cohorts | DLT is defined as 1 of the following toxicities considered by the investigator to be related to study treatment: a) Grade 3 nausea, vomiting or diarrhea that resolved to Grade less than or equal to (≤) 1 within 7 days, b) Grade 3 rash or photosensitivity that resolved to Grade ≤2 within 7 days, c) Grade 3 cutaneous squamous cell carcinoma (cuSCC) that was subsequently resected, d) Grade greater than or equal to (≥) 3 fatigue or hyperuricemia that resolved to Grade ≤2 within 7 days, e) Grade 3 fever, f) Grade 3 or 4 elevation of serum creatine phosphokinase (CPK) levels, which is asymptomatic, deemed by the investigator to be clinically insignificant and that returned to Grade ≤2 during the 14-day cobimetinib treatment holiday, g) Grade ≥3 febrile neutropenia, h) Grade ≥4 neutropenia (absolute neutrophil count [ANC] less than <500/microliter [μL]), i) Grade ≥4 thrombocytopenia, j) Grade ≥4 anemia, k) Grade ≥3 elevation of total bilirubin, hepatic transaminase or alkaline phosphatase. | 28 Days |
| Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES | The highest dose level(s) at which fewer than one-third of participants experienced a DLT was declared the MTD. DLT is defined as 1 of the following toxicities considered by the investigator to be related to study treatment: a) Grade 3 nausea, vomiting or diarrhea that resolved to Grade ≤1 within 7 days, b) Grade 3 rash/photosensitivity that resolved to Grade ≤2 within 7 days, c) Grade 3 cuSCC that was subsequently resected, d) Grade ≥3 fatigue/hyperuricemia that resolved to Grade ≤2 within 7 days, e) Grade 3 fever, f) Grade 3 or 4 elevation of serum CPK levels, which is asymptomatic, deemed to be clinically insignificant and returns to Grade ≤2 during the 14-day cobimetinib treatment holiday, g) Grade ≥3 febrile neutropenia, h) Grade ≥4 neutropenia (ANC <500/ μL), i) Grade ≥4 thrombocytopenia, j) Grade ≥4 anemia, k) Grade ≥3 elevation of total bilirubin, hepatic transaminase or alkaline phosphatase. | 28 Days |
| Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 1, Cycle 1 | Cycle 1: predose (0 hours [hr]) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (V) 1.1 | Tumor response of CR or PR is considered as objective response. CR: disappearance of all target lesions, reduction in short axis <10 millimeters in pathological lymph nodes (target and non-target lesions); PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Responses were confirmed by repeat assessments ≥4 weeks after initial documentation. |
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Inclusion Criteria:
Participants with histologically confirmed melanoma (unresectable Stage IIIc and Stage IV metastatic melanoma, as defined by American Joint Committee on Cancer [AJCC])
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V) 1.1
Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to (</=) 1
Participants must
Life expectancy >/=12 weeks
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Department of Medicine | Los Angeles | California | 90024 | United States | ||
| University of California at San Francisco |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32746839 | Derived | Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x. | |
| 25037139 |
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Participants data were pooled across dose/regimen cohorts from two stages and analyzed separately per final analysis for vemurafenib-PD and BRAFi-naive participants who received cobimetinib and vemurafenib. Data is presented based on the final CSR. As of 2017 per-cohort data were not collected
Study included two stages. Stage 1: dose escalation stage (DES), consisted of 9 "Cobimetinib + Vemurafenib" combination arms and 1 Cobimetinib monotherapy. Stage 2: cohort expansion stage (CES), consisted of 2 "Cobimetinib + Vemurafenib" combination arms, treated with recommended phase 2 dose.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vemurafenib PD Participants | All participants who progressed on vemurafenib monotherapy immediately prior to enrollment into this study were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. |
| 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 20, 2016 |
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| DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Experimental | Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Experimental | Participants will receive oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Experimental | Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| Cobimetinib Monotherapy (100 mg or 60 mg) | Experimental | Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Experimental | Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
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| vemurafenib | Drug | Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| Cmax of Cobimetinib on Day 1, Cycle 1 in Cohort 3 | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Time Taken to Reach Maximum Plasma Concentration (Tmax) of Cobimetinib on Day 1, Cycle 1 | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Area Under Concentration Versus Time Curve (AUC) Over a Period of 24 Hours (AUC0-24) of Cobimetinib on Day 1, Cycle 1 | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| AUC0-24 of Cobimetinib on Day 1, Cycle 1 of Cohort 3 | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Cmax of Cobimetinib on Day 14 (Steady State), Cycle 1 | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
| Tmax of Cobimetinib on Day 14 (Steady State), Cycle 1 | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
| AUC0-24 of Cobimetinib on Day 14, Cycle 1 | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
| Clearance (CL) of Cobimetinib on Day 14 (Steady State), Cycle 1 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
| Cmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study | Predose (0 hr) on Days -1, 1; 2, 4, 6, 8 hr postdose on Day -1 |
| Cmax of Vemurafenib on Day -1, Cycle 1 of Cohorts 1C and 2A in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study | Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1 |
| Tmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study | Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1 |
| Cmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants | Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Cmax of Vemurafenib on Day 1, Cycle 1 in Cohort 1A in BRAFi-naïve Participants | Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Tmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants | Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| Cmax of Vemurafenib on Day 14, Cycle 1 | Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14 |
| Tmax of Vemurafenib on Day 14, Cycle 1 | Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14 |
| Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression (up to 82 months) |
| Percentage of Participants With Disease Progression According to RECIST V 1.1 | Progressive disease (PD) according to RECIST V 1.1: at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (nadir), including baseline; in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of 1 or more lesions is also considered as progression. | Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression or death (up to 82 months) |
| Median Duration of Response (DOR) | Duration of response, defined as the time from first occurrence of a documented objective response until the time of disease progression, as determined by investigator review of tumor assessments using RECIST v 1.1, or death from any cause during the study (that is within 30 days after the last dose of study treatment). | Time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months) |
| Overall Survival (OS) | OS was defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up. OS analyzed using Kaplan-Meier estimate. | Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression or death (up to 82 months) |
| Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2 | The pharmacodynamic effect of cobimetinib in combination with vemurafenib was assessed by measuring changes in FDG uptake as characterized by the lean body mass corrected (LBM) maximum standardized uptake value (SUV max) measurement using FDG-PET. Post-baseline timepoint Cycle 1 was averaged between Days 10 to 14 and Cycle 2 for Days 14+7. | Cycle 1 (Days 10 to 14), Cycle 2 (Days 14+7) |
| Pharmacodynamics: Number of Participants With Mitogen-Activated Protein Kinase (MAPK) Inhibition, as Assessed by Immunohistochemistry (IHC) | Changes in effector molecules of the MAPK pathway that are directly or indirectly affected by BRAF and MEK inhibition (including but not limited to ERK and phosphorylated ERK and MEK) by IHC using biopsies at baseline, between Days 10-14 of Cycle 1, and at disease progression. IHC is a staining process performed on fresh/frozen tumor tissue samples. | At baseline; Cycle 1: Day 14; at disease progression (Up to 32 months) |
| San Francisco |
| California |
| 94115 |
| United States |
| The Angeles Clinic and Research Institute, Santa Monica Office | Santa Monica | California | 90025 | United States |
| University of Colorado; Anschutz Cancer Pavilion | Aurora | Colorado | 80045 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Indiana University - Department of Medicine, Division of Gastroenterology/Hepatology | Indianapolis | Indiana | 46202 | United States |
| Karmanos Cancer Inst. ; Hudson Webber; Cancer Research Building | Detroit | Michigan | 48201 | United States |
| New York University Medical Center | New York | New York | 10036 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Peter Maccallum Cancer Institute; Medical Oncology | Melbourne | Victoria | 3000 | Australia |
| Derived |
| Ribas A, Gonzalez R, Pavlick A, Hamid O, Gajewski TF, Daud A, Flaherty L, Logan T, Chmielowski B, Lewis K, Kee D, Boasberg P, Yin M, Chan I, Musib L, Choong N, Puzanov I, McArthur GA. Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study. Lancet Oncol. 2014 Aug;15(9):954-65. doi: 10.1016/S1470-2045(14)70301-8. Epub 2014 Jul 15. |
| 22651703 | Derived | Baudy AR, Dogan T, Flores-Mercado JE, Hoeflich KP, Su F, van Bruggen N, Williams SP. FDG-PET is a good biomarker of both early response and acquired resistance in BRAFV600 mutant melanomas treated with vemurafenib and the MEK inhibitor GDC-0973. EJNMMI Res. 2012 May 31;2(1):22. doi: 10.1186/2191-219X-2-22. |
| FG001 | BRAFi-naïve Participants | All participants who were previously untreated or previously treated but naïve to BRAF or MEK inhibitor therapy were considered as BRAFi-naïve participants. These participants were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. |
| FG002 | Cobimetinib Monotherapy (100 mg or 60 mg) | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| NOT COMPLETED |
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Demographic data was not reported across dose/regimen cohort per final analysis, as it was pooled across separately for vemurafenib-PD and BRAFi-naive participants who received cobimetinib and vemurafenib. Data is presented based on the final CSR. As of 2017 per-cohort data were not collected
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| ID | Title | Description |
|---|---|---|
| BG000 | Vemurafenib PD Participants | All participants who progressed on vemurafenib monotherapy immediately prior to enrollment into this study were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. |
| BG001 | BRAFi-naïve Participants | All participants who were previously untreated or previously treated but naïve to BRAF or MEK inhibitor therapy were considered as BRAFi-naïve participants. These participants were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. |
| BG002 | Cobimetinib Monotherapy (100 mg or 60 mg) | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| BG003 | 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, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | 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 | |||||||||||||||||||||||||||||||||
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| Primary | Number of Participants With Dose-Limiting Toxicities (DLTs) During DES in Combination Cohorts | DLT is defined as 1 of the following toxicities considered by the investigator to be related to study treatment: a) Grade 3 nausea, vomiting or diarrhea that resolved to Grade less than or equal to (≤) 1 within 7 days, b) Grade 3 rash or photosensitivity that resolved to Grade ≤2 within 7 days, c) Grade 3 cutaneous squamous cell carcinoma (cuSCC) that was subsequently resected, d) Grade greater than or equal to (≥) 3 fatigue or hyperuricemia that resolved to Grade ≤2 within 7 days, e) Grade 3 fever, f) Grade 3 or 4 elevation of serum creatine phosphokinase (CPK) levels, which is asymptomatic, deemed by the investigator to be clinically insignificant and that returned to Grade ≤2 during the 14-day cobimetinib treatment holiday, g) Grade ≥3 febrile neutropenia, h) Grade ≥4 neutropenia (absolute neutrophil count [ANC] less than <500/microliter [μL]), i) Grade ≥4 thrombocytopenia, j) Grade ≥4 anemia, k) Grade ≥3 elevation of total bilirubin, hepatic transaminase or alkaline phosphatase. | Safety-evaluable population (SEP) included all participants who received at least one dose of study drug. SEP participants who received combination study treatment (cobimetinib + Vemurafenib) were included in the analysis of this outcome. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Number | participants | 28 Days |
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| Primary | Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES | The highest dose level(s) at which fewer than one-third of participants experienced a DLT was declared the MTD. DLT is defined as 1 of the following toxicities considered by the investigator to be related to study treatment: a) Grade 3 nausea, vomiting or diarrhea that resolved to Grade ≤1 within 7 days, b) Grade 3 rash/photosensitivity that resolved to Grade ≤2 within 7 days, c) Grade 3 cuSCC that was subsequently resected, d) Grade ≥3 fatigue/hyperuricemia that resolved to Grade ≤2 within 7 days, e) Grade 3 fever, f) Grade 3 or 4 elevation of serum CPK levels, which is asymptomatic, deemed to be clinically insignificant and returns to Grade ≤2 during the 14-day cobimetinib treatment holiday, g) Grade ≥3 febrile neutropenia, h) Grade ≥4 neutropenia (ANC <500/ μL), i) Grade ≥4 thrombocytopenia, j) Grade ≥4 anemia, k) Grade ≥3 elevation of total bilirubin, hepatic transaminase or alkaline phosphatase. | Safety-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Number | mg | 28 Days |
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| Primary | Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 1, Cycle 1 | PK population included all participants who received study treatment and had at least one vemurafenib and cobimetinib plasma concentration available. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Cycle 1: predose (0 hours [hr]) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
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| Primary | Cmax of Cobimetinib on Day 1, Cycle 1 in Cohort 3 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
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| Primary | Time Taken to Reach Maximum Plasma Concentration (Tmax) of Cobimetinib on Day 1, Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Median | Full Range | hours | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
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| Primary | Area Under Concentration Versus Time Curve (AUC) Over a Period of 24 Hours (AUC0-24) of Cobimetinib on Day 1, Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
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| Primary | AUC0-24 of Cobimetinib on Day 1, Cycle 1 of Cohort 3 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Mean | Standard Deviation | ng*h/mL | Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
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| Primary | Cmax of Cobimetinib on Day 14 (Steady State), Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
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| Primary | Tmax of Cobimetinib on Day 14 (Steady State), Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Median | Full Range | hours | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
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| Primary | AUC0-24 of Cobimetinib on Day 14, Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
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| Primary | Clearance (CL) of Cobimetinib on Day 14 (Steady State), Cycle 1 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour (L/h) | Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 |
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| Primary | Cmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study | PK population. Here, number of participants analyzed = participants who were previously treated with vemurafenib prior to enrollment into this study. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliliter (mcg/mL) | Predose (0 hr) on Days -1, 1; 2, 4, 6, 8 hr postdose on Day -1 |
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| Primary | Cmax of Vemurafenib on Day -1, Cycle 1 of Cohorts 1C and 2A in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study | PK population. Here, number of participants analyzed = participants who were previously treated with vemurafenib prior to enrollment into this study. | Posted | Mean | Standard Deviation | mcg/mL | Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1 |
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| Primary | Tmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study | PK population. Here, number of participants analyzed = participants who were previously treated with vemurafenib prior to enrollment into this study. | Posted | Median | Full Range | hours | Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1 |
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| Primary | Cmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants | PK population.Here, number of participants analyzed = participants who were BRAFi-naïve participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| |||||||||||||||||||||||||||||||||||||||||
| Primary | Cmax of Vemurafenib on Day 1, Cycle 1 in Cohort 1A in BRAFi-naïve Participants | PK population. Here, number of participants analyzed = participants who were BRAFi-naïve participants. | Posted | Mean | Standard Deviation | mcg/mL | Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
|
| ||||||||||||||||||||||||||||||||||||||||
| Primary | Tmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants | PK population. Here, number of participants analyzed = participants who were BRAFi-naïve participants. | Posted | Median | Full Range | hours | Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 |
| |||||||||||||||||||||||||||||||||||||||||
| Primary | Cmax of Vemurafenib on Day 14, Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14 |
| |||||||||||||||||||||||||||||||||||||||||
| Primary | Tmax of Vemurafenib on Day 14, Cycle 1 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Median | Full Range | hours | Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14 |
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (V) 1.1 | Tumor response of CR or PR is considered as objective response. CR: disappearance of all target lesions, reduction in short axis <10 millimeters in pathological lymph nodes (target and non-target lesions); PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Responses were confirmed by repeat assessments ≥4 weeks after initial documentation. | Efficacy evaluable population who had measurable disease at baseline and had either a post-baseline tumour assessment or progressed before any tumour assessment was included in the analysis of this outcome. | Posted | Number | 95% Confidence Interval | percentage of participants | Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression (up to 82 months) |
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Disease Progression According to RECIST V 1.1 | Progressive disease (PD) according to RECIST V 1.1: at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (nadir), including baseline; in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of 1 or more lesions is also considered as progression. | Efficacy evaluable population who had measurable disease at baseline and had either a post-baseline tumour assessment or progressed before any tumour assessment was included in the analysis of this outcome. | Posted | Number | percentage of participants | Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression or death (up to 82 months) |
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Median Duration of Response (DOR) | Duration of response, defined as the time from first occurrence of a documented objective response until the time of disease progression, as determined by investigator review of tumor assessments using RECIST v 1.1, or death from any cause during the study (that is within 30 days after the last dose of study treatment). | Efficacy evaluable population who had measurable disease at baseline and had either a post-baseline tumour assessment or progressed before any tumour assessment was included in the analysis of this outcome. Number of participants analysed who were evaluated for this outcome measure. | Posted | Median | 95% Confidence Interval | months | Time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months) |
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | OS was defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up. OS analyzed using Kaplan-Meier estimate. | Efficacy evaluable population who had measurable disease at baseline and had either a post-baseline tumour assessment or progressed before any tumour assessment was included in the analysis of this outcome. | Posted | Median | Full Range | months | Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression or death (up to 82 months) |
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2 | The pharmacodynamic effect of cobimetinib in combination with vemurafenib was assessed by measuring changes in FDG uptake as characterized by the lean body mass corrected (LBM) maximum standardized uptake value (SUV max) measurement using FDG-PET. Post-baseline timepoint Cycle 1 was averaged between Days 10 to 14 and Cycle 2 for Days 14+7. | Safety evaluable population who received combination study treatment (Cobimetinib + Vemurafenib) was included in the analysis of this outcome. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Mean | Standard Deviation | Percent change in FDG-PET | Cycle 1 (Days 10 to 14), Cycle 2 (Days 14+7) |
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacodynamics: Number of Participants With Mitogen-Activated Protein Kinase (MAPK) Inhibition, as Assessed by Immunohistochemistry (IHC) | Changes in effector molecules of the MAPK pathway that are directly or indirectly affected by BRAF and MEK inhibition (including but not limited to ERK and phosphorylated ERK and MEK) by IHC using biopsies at baseline, between Days 10-14 of Cycle 1, and at disease progression. IHC is a staining process performed on fresh/frozen tumor tissue samples. | Number of participants analyzed=number of participants available for analysis of this outcome measure. | Posted | Number | participants | At baseline; Cycle 1: Day 14; at disease progression (Up to 32 months) |
|
Up to 82 months
Safety data was not reported per dose/regimen cohort. Due to final analysis data for adverse events were reported collectively for both the reporting groups- Vemurafenib PD and BRAFi-naïve participants along with Cobimetinib Monotherapy. Data is presented based on the final CSR. As of 2017 per-cohort data were not collected.
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 | Vemurafenib PD Participants | All participants who progressed on vemurafenib monotherapy immediately prior to enrollment into this study were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. | 21 | 66 | 64 | 66 | ||
| EG001 | BRAFi-naïve Participants | All participants who were previously untreated or previously treated but naïve to BRAF or MEK inhibitor therapy were considered as BRAFi-naïve participants. These participants were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. | 36 | 63 | 63 | 63 | ||
| EG002 | Cobimetinib Monotherapy (100 mg or 60 mg) | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 0 | 2 | 2 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congestive cardiomyopathy | Cardiac disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Iridocyclitis | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Biloma | Hepatobiliary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Ophthalmic herpes zoster | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia chlamydial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsil cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vogt-koyanagi-harada syndrome | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Face Oedema | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haemtemesis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypersenstivity | Immune system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Streptococcal bacteraemia | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Adrenal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Non-systematic Assessment |
| |
| Glomerulonephritis | Renal and urinary disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chorioretinopathy | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Salpingo-Oophorectomy unilateral | Surgical and medical procedures | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Keratosis pilaris | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Panniculitis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rosacea | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Blood alkaline phophatase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Gamma-glutamyl transferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Sunburn | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 20.0 | Non-systematic Assessment |
| |
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Non-systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
| Mar 19, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| 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 |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C574276 | cobimetinib |
| D000077484 | Vemurafenib |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib |
Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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| OG003 | DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG004 | DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG005 | DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG006 | DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG007 | DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG008 | DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG009 | CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
| OG010 | CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib | Participants received oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. |
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All participants who were previously untreated or previously treated but naïve to BRAF or MEK inhibitor therapy were considered as BRAFi-naïve participants. These participants were treated with vemurafenib in combination with cobimetinib at a particular dose combination and dosing schedule depending on the cohort in which they were enrolled until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.
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