Trial Outcomes & Findings for A Study of Vemurafenib and GDC-0973 (Cobimetinib) in Participants With BRAFV600E Mutation-Positive Metastatic Melanoma (NCT NCT01271803)

NCT ID: NCT01271803

Last Updated: 2019-07-29

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

131 participants

Primary outcome timeframe

Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Results posted on

2019-07-29

Participant Flow

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.

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

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	66	63	2
Overall Study COMPLETED	11	24	0
Overall Study NOT COMPLETED	55	39	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Progressive disease	0	0	2
Overall Study Death	53	34	0
Overall Study Withdrawal by Subject	1	5	0
Overall Study Lost to Follow-up	1	0	0

Baseline Characteristics

A Study of Vemurafenib and GDC-0973 (Cobimetinib) in Participants With BRAFV600E Mutation-Positive Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vemurafenib PD Participants n=66 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.	BRAFi-naïve Participants n=63 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.	Cobimetinib Monotherapy (100 mg or 60 mg) n=2 Participants 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.	Total n=131 Participants Total of all reporting groups
Age, Continuous	53.0 years STANDARD_DEVIATION 14.8 • n=93 Participants	54.0 years STANDARD_DEVIATION 13.0 • n=4 Participants	62.5 years STANDARD_DEVIATION 9.2 • n=27 Participants	53.6 years STANDARD_DEVIATION 13.9 • n=483 Participants
Sex: Female, Male Female	24 Participants n=93 Participants	28 Participants n=4 Participants	1 Participants n=27 Participants	53 Participants n=483 Participants
Sex: Female, Male Male	42 Participants n=93 Participants	35 Participants n=4 Participants	1 Participants n=27 Participants	78 Participants n=483 Participants

PRIMARY outcome

Timeframe: 28 Days

Population: 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.

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=27 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=5 Participants 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.	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.	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.
Number of Participants With Dose-Limiting Toxicities (DLTs) During DES in Combination Cohorts	0 participants	0 participants	1 participants	0 participants	2 participants	0 participants	0 participants	0 participants	1 participants	—	—

PRIMARY outcome

Timeframe: 28 Days

Population: Safety-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=63 Participants Participants received oral 60 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.	DES (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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES Cobimetinib dose (21/7 dosing schedule)	60 mg	—	—	—	—	—	—	—	—	—	—
Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES Vemurafenib dose (21/7 dosing schedule)	960 mg	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hours [hr]) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: 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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=26 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=5 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=27 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=38 Participants 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.	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.
Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 1, Cycle 1	159 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 110	146 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 100	121 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 96	136 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 81	130 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53	133 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 37	146 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 79	93.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 26	84.3 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 67	105 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 64	—

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants Participants received oral 60 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.	DES (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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Cmax of Cobimetinib on Day 1, Cycle 1 in Cohort 3	51.6 ng/mL Standard Deviation 50.1	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=26 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=2 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=5 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=27 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=38 Participants 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.
Time Taken to Reach Maximum Plasma Concentration (Tmax) of Cobimetinib on Day 1, Cycle 1	4.00 hours Interval 2.0 to 5.5	4.0 hours Interval 2.0 to 27.0	4.00 hours Interval 1.0 to 25.0	2.03 hours Interval 2.0 to 24.0	3.99 hours Interval 1.0 to 6.2	4.02 hours Interval 4.0 to 4.1	4.03 hours Interval 4.0 to 4.3	3.05 hours Interval 2.0 to 4.1	4.00 hours Interval 2.0 to 6.0	4.00 hours Interval 0.5 to 6.0	4.00 hours Interval 1.0 to 24.0

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=26 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=5 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=27 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=38 Participants 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.	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.
Area Under Concentration Versus Time Curve (AUC) Over a Period of 24 Hours (AUC0-24) of Cobimetinib on Day 1, Cycle 1	2280 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 90	1990 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 99	1790 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 88	1300 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 35	1850 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 35	1600 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 29	2300 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 100	1410 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 29	1220 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 63	1530 nanogramshours per milliliter (ngh/mL) Geometric Coefficient of Variation 65	—

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants Participants received oral 60 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.	DES (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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
AUC0-24 of Cobimetinib on Day 1, Cycle 1 of Cohort 3	727 ng*h/mL Standard Deviation 556	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=32 Participants 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.
Cmax of Cobimetinib on Day 14 (Steady State), Cycle 1	342 ng/mL Geometric Coefficient of Variation 130	307 ng/mL Geometric Coefficient of Variation 75	232 ng/mL Geometric Coefficient of Variation 80	239 ng/mL Geometric Coefficient of Variation 14	414 ng/mL Geometric Coefficient of Variation 16	195 ng/mL Geometric Coefficient of Variation 48	383 ng/mL Geometric Coefficient of Variation 50	215 ng/mL Geometric Coefficient of Variation 19	350 ng/mL Geometric Coefficient of Variation 37	177 ng/mL Geometric Coefficient of Variation 74	200 ng/mL Geometric Coefficient of Variation 91

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=32 Participants 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.
Tmax of Cobimetinib on Day 14 (Steady State), Cycle 1	2.0 hours Interval 0.98 to 4.0	3.98 hours Interval 2.0 to 7.0	4.02 hours Interval 0.5 to 8.0	4.00 hours Interval 4.0 to 4.1	6.00 hours Interval 4.9 to 6.1	6.0 hours Interval 2.0 to 6.0	4.03 hours Interval 2.2 to 6.1	4.08 hours Interval 4.0 to 6.1	4.00 hours Interval 3.9 to 4.1	4.04 hours Interval 2.0 to 8.0	4.00 hours Interval 0.0 to 8.0

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=32 Participants 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.
AUC0-24 of Cobimetinib on Day 14, Cycle 1	5180 ng*h/mL Geometric Coefficient of Variation 170	4800 ng*h/mL Geometric Coefficient of Variation 76	3540 ng*h/mL Geometric Coefficient of Variation 83	4500 ng*h/mL Geometric Coefficient of Variation 17	7020 ng*h/mL Geometric Coefficient of Variation 27	3820 ng*h/mL Geometric Coefficient of Variation 48	6360 ng*h/mL Geometric Coefficient of Variation 46	3520 ng*h/mL Geometric Coefficient of Variation 35	5790 ng*h/mL Geometric Coefficient of Variation 36	2540 ng*h/mL Geometric Coefficient of Variation 84	3220 ng*h/mL Geometric Coefficient of Variation 124

PRIMARY outcome

Timeframe: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=32 Participants 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.
Clearance (CL) of Cobimetinib on Day 14 (Steady State), Cycle 1	11.6 Liters per hour (L/h) Geometric Coefficient of Variation 170	12.5 Liters per hour (L/h) Geometric Coefficient of Variation 76	17.0 Liters per hour (L/h) Geometric Coefficient of Variation 83	13.3 Liters per hour (L/h) Geometric Coefficient of Variation 17	8.55 Liters per hour (L/h) Geometric Coefficient of Variation 27	21.0 Liters per hour (L/h) Geometric Coefficient of Variation 48	15.7 Liters per hour (L/h) Geometric Coefficient of Variation 46	17.0 Liters per hour (L/h) Geometric Coefficient of Variation 35	13.8 Liters per hour (L/h) Geometric Coefficient of Variation 36	23.6 Liters per hour (L/h) Geometric Coefficient of Variation 84	18.6 Liters per hour (L/h) Geometric Coefficient of Variation 124

PRIMARY outcome

Timeframe: Predose (0 hr) on Days -1, 1; 2, 4, 6, 8 hr postdose on Day -1

Population: PK population. Here, number of participants analyzed = participants who were previously treated with vemurafenib prior to enrollment into this study.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=6 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=1 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=15 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=19 Participants 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.	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.	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.	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.
Cmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study	36.4 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 58	34.3 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 34	60.9 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 32	56.0 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 16	36.4 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 19	48.2 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation NA Geometric coefficient of variation is not applicable as only 1 participant had evaluable data.	40.9 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 110	48.6 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 37	—	—	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1

Population: PK population. Here, number of participants analyzed = participants who were previously treated with vemurafenib prior to enrollment into this study.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
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	38.8 mcg/mL Standard Deviation 9.61	48.8 mcg/mL Standard Deviation 35.4	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1

Population: PK population. Here, number of participants analyzed = participants who were previously treated with vemurafenib prior to enrollment into this study.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=6 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=1 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=15 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=19 Participants 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.	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.
Tmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study	2.42 hours Interval 1.3 to 4.5	2.50 hours Interval 0.7 to 7.5	3.69 hours Interval 1.1 to 11.0	4.55 hours Interval 3.1 to 6.0	2.03 hours Interval 0.9 to 2.5	1.65 hours Interval 1.3 to 2.0	1.92 hours Interval 0.6 to 4.8	0.83 hours Full range is not applicable as only 1 participant had evaluable data.	2.33 hours Interval 0.3 to 8.1	1.93 hours Interval 0.6 to 7.5	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population.Here, number of participants analyzed = participants who were BRAFi-naïve participants.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=16 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=1 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=1 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=11 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=19 Participants 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.	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.	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.	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.	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.
Cmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants	3.99 mcg/mL Geometric Coefficient of Variation 73	2.31 mcg/mL Geometric Coefficient of Variation NA Geometric coefficient of variation is not applicable as only 1 participant had evaluable data.	4.16 mcg/mL Geometric Coefficient of Variation 78	1.25 mcg/mL Geometric Coefficient of Variation NA Geometric coefficient of variation is not applicable as only 1 participant had evaluable data.	2.55 mcg/mL Geometric Coefficient of Variation 170	2.60 mcg/mL Geometric Coefficient of Variation 70	2.78 mcg/mL Geometric Coefficient of Variation 57	—	—	—	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population. Here, number of participants analyzed = participants who were BRAFi-naïve participants.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants Participants received oral 60 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.	DES (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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Cmax of Vemurafenib on Day 1, Cycle 1 in Cohort 1A in BRAFi-naïve Participants	2.08 mcg/mL Standard Deviation 1.64	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1

Population: PK population. Here, number of participants analyzed = participants who were BRAFi-naïve participants.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=2 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=16 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=1 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=1 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=11 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=19 Participants 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.	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.	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.	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.
Tmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants	5.2 hours Interval 4.4 to 6.0	4.15 hours Interval 1.0 to 6.0	5.17 hours Full range is not applicable as only 1 participant had evaluable data.	5.33 hours Interval 2.0 to 6.2	2.08 hours Full range is not applicable as only 1 participant had evaluable data.	4.00 hours Interval 2.0 to 6.0	4.00 hours Interval 2.0 to 6.0	4.00 hours Interval 1.0 to 24.0	—	—	—

PRIMARY outcome

Timeframe: Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=32 Participants 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.
Cmax of Vemurafenib on Day 14, Cycle 1	34.7 mcg/mL Geometric Coefficient of Variation 41	29.4 mcg/mL Geometric Coefficient of Variation 25	43.7 mcg/mL Geometric Coefficient of Variation 37	31.7 mcg/mL Geometric Coefficient of Variation 42	51.3 mcg/mL Geometric Coefficient of Variation 14	43.6 mcg/mL Geometric Coefficient of Variation 45	30.6 mcg/mL Geometric Coefficient of Variation 53	40.9 mcg/mL Geometric Coefficient of Variation 20	33.7 mcg/mL Geometric Coefficient of Variation 16	33.3 mcg/mL Geometric Coefficient of Variation 58	36.3 mcg/mL Geometric Coefficient of Variation 29

PRIMARY outcome

Timeframe: Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14

Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=8 Participants 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.	DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib n=3 Participants 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.	DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib n=4 Participants 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.	DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib n=3 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=25 Participants 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.	CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib n=32 Participants 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.
Tmax of Vemurafenib on Day 14, Cycle 1	1.98 hours Interval 0.0 to 7.7	2.15 hours Interval 0.0 to 7.3	1.95 hours Interval 0.0 to 8.0	1.98 hours Interval 0.3 to 6.5	0.33 hours Interval 0.2 to 8.2	5.6 hours Interval 1.7 to 5.6	1.05 hours Interval 0.0 to 6.4	1.83 hours Interval 0.8 to 4.4	1.85 hours Interval 0.1 to 4.0	1.17 hours Interval 0.0 to 7.9	1.90 hours Interval 0.0 to 7.6

SECONDARY outcome

Timeframe: Assessed at screening (within 28 days prior to initiation of Cycle 1), every 6 weeks thereafter until disease progression (up to 82 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=66 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=63 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
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	15.2 percentage of participants Interval 7.5 to 25.5	87.3 percentage of participants Interval 76.7 to 94.4	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=66 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=63 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Percentage of Participants With Disease Progression According to RECIST V 1.1	36.4 percentage of participants	3.2 percentage of participants	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Time from first occurrence of objective response until the time of disease progression or death from any cause (up to 82 months)

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).

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=10 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=55 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Median Duration of Response (DOR)	6.8 months Interval 4.9 to 10.4	14.3 months Interval 9.7 to 23.0	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=66 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=63 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Overall Survival (OS)	8.5 months Interval 1.6 to 76.4	31.8 months Interval 2.7 to 69.2	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 (Days 10 to 14), Cycle 2 (Days 14+7)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=63 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=63 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2 Baseline (n=63,63)	8.75 Percent change in FDG-PET Standard Deviation 5.55	8.19 Percent change in FDG-PET Standard Deviation 5.00	—	—	—	—	—	—	—	—	—
Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2 Percent Change at Cycle 1 (Days 10-14) (n=59,60)	-43.33 Percent change in FDG-PET Standard Deviation 26.00	-65.74 Percent change in FDG-PET Standard Deviation 14.82	—	—	—	—	—	—	—	—	—
Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2 Percent Change at Cycle 2 (Days 14+7) (n=50,56)	-33.09 Percent change in FDG-PET Standard Deviation 35.18	-70.73 Percent change in FDG-PET Standard Deviation 17.05	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At baseline; Cycle 1: Day 14; at disease progression (Up to 32 months)

Population: Number of participants analyzed=number of participants available for analysis of this outcome measure.

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.

Outcome measures

Outcome measures
Measure	DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib n=7 Participants Participants received oral 60 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.	DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib n=5 Participants 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.	DES (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.	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.	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.	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.	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.	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.	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.	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.	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.
Pharmacodynamics: Number of Participants With Mitogen-Activated Protein Kinase (MAPK) Inhibition, as Assessed by Immunohistochemistry (IHC)	7 participants	5 participants	—	—	—	—	—	—	—	—	—

Adverse Events

Vemurafenib PD Participants

Serious events: 21 serious events

Other events: 64 other events

Deaths: 0 deaths

BRAFi-naïve Participants

Serious events: 36 serious events

Other events: 63 other events

Deaths: 0 deaths

Cobimetinib Monotherapy (100 mg or 60 mg)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER