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

Study Description

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Brief Summary:

This open-label, dose-escalation study of vemurafenib in combination with cobimetinib will evaluate the safety, tolerability and pharmacokinetics in participants with BRAFV600 mutation-positive metastatic melanoma. Participants with previously untreated, BRAFV600E mutation-positive, locally advanced/unresectable or metastatic melanoma or those who have progressed on vemurafenib monotherapy immediately prior to enrolling in this trial are eligible. Participants will be assigned to different cohorts with escalating oral doses of vemurafenib and cobimetinib. This study consists of 2 stages, Stage 1 (Dose Escalation Stage [DES] and Cohort Expansion Stage [CES]) and the anticipated time on study treatment is until disease progression, unacceptable toxicity or any other discontinuation criterion is met.

Condition or disease	Intervention/treatment	Phase
Malignant Melanoma	Drug: Cobimetinib; Drug: vemurafenib	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	131 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase IB, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of Vemurafenib in Combination With GDC-0973 (Cobimetinib) When Administered in BRAFV600E Mutation-Positive Patients Previously Treated (But Without Prior Exposure to BRAF or MEK Inhibitor Therapy) or Previously Untreated for Locally Advanced/Unresectable or Metastatic Melanoma or Those Who Have Progressed After Treatment With Vemurafenib
Actual Study Start Date :	February 17, 2011
Actual Primary Completion Date :	October 1, 2013
Estimated Study Completion Date :	June 29, 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: DES (Cohort 1): 60 mg Cobimetinib + 720 mg Vemurafenib; Participants will receive oral 60 milligrams (mg) cobimetinib once daily (QD) on Days 1-14, followed by 14 days off on Days 15-28 (14/14 dosing schedule) and oral 720 mg vemurafenib twice daily (BID) on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on Days 1-21, followed by 7 days off on Days 22-28 (21/7 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 1C): 60 mg Cobimetinib + 720 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on Days 1-28 (28/0 dosing schedule) and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 1D): 60 mg Cobimetinib + 960 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on 28/0 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 2): 80 mg Cobimetinib + 720 mg Vemurafenib; Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 2A): 100 mg Cobimetinib + 720 mg Vemurafenib; Participants will receive oral 100 mg cobimetinib QD on 14/14 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 3): 60 mg Cobimetinib + 960 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: DES (Cohort 4): 80 mg Cobimetinib + 960 mg Vemurafenib; Participants will receive oral 80 mg cobimetinib QD on 14/14 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: Cobimetinib Monotherapy (100 mg or 60 mg); Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule, or oral 100 mg cobimetinib QD on 14/14 dosing schedule of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973
Experimental: CES (Cohort 1A): 60 mg Cobimetinib + 720 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 720 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Experimental: CES (Cohort 1B): 60 mg Cobimetinib + 960 mg Vemurafenib; Participants will receive oral 60 mg cobimetinib QD on 21/7 dosing schedule and oral 960 mg vemurafenib BID on Days 1-28 of every cycle (1 Cycle=28 Days), until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.	Drug: Cobimetinib; Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Other Name: GDC-0973 Drug: vemurafenib; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Outcome Measures

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Primary Outcome Measures :

1. Number of Participants With Dose-Limiting Toxicities (DLTs) During DES in Combination Cohorts [ Time Frame: 28 Days ]
   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.
2. Maximum Tolerated Doses (MTD) of Vemurafenib and Cobimetinib When Administered in Combination in DES [ Time Frame: 28 Days ]
   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.
3. Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 1, Cycle 1 [ Time Frame: Cycle 1: predose (0 hours [hr]) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
4. Cmax of Cobimetinib on Day 1, Cycle 1 in Cohort 3 [ Time Frame: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
5. Time Taken to Reach Maximum Plasma Concentration (Tmax) of Cobimetinib on Day 1, Cycle 1 [ Time Frame: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
6. Area Under Concentration Versus Time Curve (AUC) Over a Period of 24 Hours (AUC0-24) of Cobimetinib on Day 1, Cycle 1 [ Time Frame: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
7. AUC0-24 of Cobimetinib on Day 1, Cycle 1 of Cohort 3 [ Time Frame: Cycle 1: predose (0 hr) on Days 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
8. Cmax of Cobimetinib on Day 14 (Steady State), Cycle 1 [ Time Frame: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 ]
9. Tmax of Cobimetinib on Day 14 (Steady State), Cycle 1 [ Time Frame: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 ]
10. AUC0-24 of Cobimetinib on Day 14, Cycle 1 [ Time Frame: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 ]
11. Clearance (CL) of Cobimetinib on Day 14 (Steady State), Cycle 1 [ Time Frame: Cycle 1: predose (0 hr) on Days 8, 14; 0.5, 1, 2, 4, 6 hr postdose on Day 14 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
12. Cmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study [ Time Frame: Predose (0 hr) on Days -1, 1; 2, 4, 6, 8 hr postdose on Day -1 ]
13. 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 [ Time Frame: Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1 ]
14. Tmax of Vemurafenib on Day -1, Cycle 1 in Participants Previously Treated With Vemurafenib Prior to Enrollment Into This Study [ Time Frame: Predose (0 hr) on Day -1, 1; 2, 4, 6, 8 hr postdose on Day -1 ]
15. Cmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants [ Time Frame: Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
16. Cmax of Vemurafenib on Day 1, Cycle 1 in Cohort 1A in BRAFi-naïve Participants [ Time Frame: Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
17. Tmax of Vemurafenib on Day 1, Cycle 1 in BRAFi-naïve Participants [ Time Frame: Predose (0 hr) on Day 1, 2; 0.5, 1, 2, 4, 6 hr postdose on Day 1 ]
18. Cmax of Vemurafenib on Day 14, Cycle 1 [ Time Frame: Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14 ]
19. Tmax of Vemurafenib on Day 14, Cycle 1 [ Time Frame: Predose (0 hr) on Days 14, 15; 0.5, 1, 2, 4, 6, 8 hr postdose on Day 14 ]

Secondary Outcome Measures :

1. 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 [ Time Frame: Screening to up to data cut-off (01 October 2013) (assessed at screening [within 28 days prior to initiation of Cycle 1], every 6 weeks thereafter until disease progression or death or data cut-off [01 October 2013]) up to 32 months ]
   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.
2. Percentage of Participants With Disease Progression According to RECIST V 1.1 [ Time Frame: Screening to up to data cut-off (01 October 2013) (assessed at screening [within 28 days prior to initiation of Cycle 1], every 6 weeks thereafter until disease progression or death or data cut-off [01 October 2013]) up to 32 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.
3. Median Duration of Response (DOR) [ Time Frame: Screening to up to data cut-off (01 October 2013) (assessed at screening [within 28 days prior to initiation of Cycle 1], every 6 weeks thereafter until disease progression or death or data cut-off [01 October 2013]) up to 32 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).
4. Overall Survival (OS) [ Time Frame: Screening to up to data cut-off (01 October 2013) (assessed at screening [within 28 days prior to initiation of Cycle 1], every 6 weeks thereafter until disease progression or death or data cut-off [01 October 2013]) up to 32 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.
5. Average Percent Change From Baseline in Fluorodeoxyglucose-positron Emission Tomography (FDG-PET) at Cycle 1 and Cycle 2 [ Time Frame: Cycle 1 (Days 10 to 14), Cycle 2 (Days 14+7) ]
   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.
6. Pharmacodynamics: Number of Participants With Mitogen-Activated Protein Kinase (MAPK) Inhibition, as Assessed by Immunohistochemistry (IHC) [ Time Frame: At baseline; Cycle 1: Day 14; at disease progression (Up to 32 months) ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Participants with histologically confirmed melanoma (unresectable Stage IIIc and Stage IV metastatic melanoma, as defined by American Joint Committee on Cancer [AJCC])
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V) 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to (</=) 1

• Participants must

  1. be previously untreated for locally advanced/unresectable or metastatic melanoma or
  2. previously treated but without prior exposure to any BRAF or MEK inhibitor therapy or
  3. progressed on vemurafenib while participating in a Phase I (including clinical pharmacology studies), II, or III clinical study or expanded access programs (EAP) immediately prior to enrollment in this study or
  4. progressed on vemurafenib administered in a postmarketing setting immediately prior to enrollment in this study.
• Life expectancy >/=12 weeks

Exclusion Criteria:

• History of prior significant toxicity from another RAF or MEK pathway inhibitor requiring discontinuation of treatment
• Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment
• Experimental therapy within 4 weeks prior to first dose of study drug treatment except vemurafenib
• Major surgery within 4 weeks of first dose of study drug treatment or planning a major surgery during the study

Contacts and Locations

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Locations

United States, California
UCLA Department of Medicine
Los Angeles, California, United States, 90024
University of California at San Francisco
San Francisco, California, United States, 94115
The Angeles Clinic and Research Institute, Santa Monica Office
Santa Monica, California, United States, 90025
United States, Colorado
University of Colorado; Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University - Department of Medicine, Division of Gastroenterology/Hepatology
Indianapolis, Indiana, United States, 46202
United States, Michigan
Karmanos Cancer Inst. ; Hudson Webber; Cancer Research Building
Detroit, Michigan, United States, 48201
United States, New York
New York University Medical Center
New York, New York, United States, 10036
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Australia, Victoria
Peter Maccallum Cancer Institute; Medical Oncology
Melbourne, Victoria, Australia, 3000

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:	Clinical Trials	Hoffmann-La Roche

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ribas A, Gonzalez R, Pavlick A, Hamid O, Gajewski TF, Daud A, Flaherty L, Logan T, Chmielowski B, Lewis K, Kee D, Boasberg P, Yin M, Chan I, Musib L, Choong N, Puzanov I, McArthur GA. Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study. Lancet Oncol. 2014 Aug;15(9):954-65. doi: 10.1016/S1470-2045(14)70301-8. Epub 2014 Jul 15. Erratum in: Lancet Oncol. 2014 Sep;15(10):417.

Baudy AR, Dogan T, Flores-Mercado JE, Hoeflich KP, Su F, van Bruggen N, Williams SP. FDG-PET is a good biomarker of both early response and acquired resistance in BRAFV600 mutant melanomas treated with vemurafenib and the MEK inhibitor GDC-0973. EJNMMI Res. 2012 May 31;2(1):22. doi: 10.1186/2191-219X-2-22.

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01271803 History of Changes
Other Study ID Numbers:	NO25395
First Posted:	January 7, 2011
Results First Posted:	June 17, 2016
Last Update Posted:	April 9, 2018
Last Verified:	April 2018

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms	Neoplasms, Nerve Tissue; Nevi and Melanomas; Vemurafenib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action