A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma (coBRIM)

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ClinicalTrials.gov Identifier: NCT01689519

Recruitment Status : Completed

First Posted : September 21, 2012

Results First Posted : October 30, 2015

Last Update Posted : May 2, 2022

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Sponsor:

Information provided by (Responsible Party):

Hoffmann-La Roche

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Malignant Melanoma
Interventions	Drug: Placebo Drug: Vemurafenib Drug: Cobimetinib
Enrollment	495

Participant Flow

Recruitment Details
Pre-assignment Details	Written informed consent for participation in the study was obtained before performing any study-specific screening tests or evaluations.


Arm/Group Title	Cobimetinib + Vemurafenib	Placebo + Vemurafenib
Arm/Group Description	Participants received cobimetinib 6...	Participants received placebo orall...
Arm/Group Description	Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Period Title: Intent to Treat
Started	247	248
Completed	0	0
Not Completed	247	248
Reason Not Completed
Death	157	167
Lost to Follow-up	4	8
Other	2	4
Physician Decision	4	1
Study terminated by Spon6sor	59	48
Withdrawal by Subject	21	20
Period Title: Safety Population
Started	248	245
Completed	0	0
Not Completed	248	245
Reason Not Completed
Death	158	165
Lost to Follow-up	4	8
Other	2	4
Physician Decision	4	1
Study Terminated By Sponsor	60	47
Withdrawal by Subject	20	20

Baseline Characteristics

Arm/Group Title		Cobimetinib + Vemurafenib	Placebo + Vemurafenib	Total
Arm/Group Description		Participants received cobimetinib 6...	Participants received placebo orall...	Total of all reporting groups
Arm/Group Description		Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Total of all reporting groups
Overall Number of Baseline Participants		247	248	495
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	247 participants	248 participants	495 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	183 74.1%	179 72.2%	362 73.1%
	>=65 years	64 25.9%	69 27.8%	133 26.9%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	247 participants	248 participants	495 participants
		54.9 (14.0)	55.3 (13.8)	55.1 (13.9)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	247 participants	248 participants	495 participants
	Female	101 40.9%	108 43.5%	209 42.2%
	Male	146 59.1%	140 56.5%	286 57.8%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Count of Participants	Number Analyzed	247 participants	248 participants	495 participants
Asian		1	0	1
More than one race		1	1	2
Native Hawaiian or other Pacific Islande		0	1	1
Black or African American		0	0	0
White		227	235	462
Unknown or Not Reported		16	9	25
Other		2	2	4
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Count of Participants	Number Analyzed	247 participants	248 participants	495 participants
Hispanic or Latino		14	12	26
Not Hispanic or Latino		213	223	436
Not Stated		16	10	26
Unknown		4	3	7

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival
Description	Progression-free survival was defined as the time from randomization t...
Description	Progression-free survival was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause, whichever came first. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Time Frame	Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.


Arm/Group Title	Cobimetinib + Vemurafenib	Placebo + Vemurafenib
Arm/Group Description:	Participants received cobimetinib 6...	Participants received placebo orall...
Arm/Group Description:	Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed	247	248
Median (95% Confidence Interval) Unit of Measure: Months
Primary Analysis: 9 May 2014	9.90 ^[1] (9.00 to NA)	6.20 (5.55 to 7.39)
Post hoc Efficacy Analysis: 16 January 2015	12.30 (9.50 to 13.40)	7.20 (5.60 to 7.50)
Extended 5-Year Analysis: 21 July 2019	12.60 (9.50 to 14.80)	7.20 (5.60 to 7.50)

[1]

NA = not estimable, could not be calculated due to too few events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Primary Analysis 9 May 2014
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0001
	Comments	The analysis was stratified by geographic region and metastasis classification (disease stage).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95% 0.39 to 0.68
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Post hoc Efficacy Analysis: 16 January 2015
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The analysis was stratified by geographic region and metastasis classification (disease stage).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95% 0.46 to 0.72
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Extended 5-Year Analysis: 21 July 2019
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The analysis was stratified by geographic region and metastasis classification (disease stage).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95% 0.53 to 0.79
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival
Description	Overall survival was defined as the time from randomization until the ...
Description	Overall survival was defined as the time from randomization until the date of death from any cause.
Time Frame	Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.


Arm/Group Title	Cobimetinib + Vemurafenib	Placebo + Vemurafenib
Arm/Group Description:	Participants received cobimetinib 6...	Participants received placebo orall...
Arm/Group Description:	Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed	247	248
Median (95% Confidence Interval) Unit of Measure: Months
Primary Analysis 9 May 2014	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)
Post hoc Analysis 16 January 2015	NA ^[1] (20.70 to NA)	17.00 ^[1] (15.00 to NA)
Final Analysis 28 August 2015	22.30 ^[1] (20.3 to NA)	17.40 (15.00 to 19.8)
Extended 5-year Analysis 21 July 2019	22.50 (20.30 to 28.80)	17.40 (15.00 to 19.80)

[1]

NA = not estimable, could not be calculated due to too few events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Primary Analysis 9 May 2014
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0463
	Comments	The analysis was stratified by geographic region and metastasis classification (disease stage).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.645
	Confidence Interval	(2-Sided) 95% 0.42 to 1.00
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Post hoc Analysis 16 January 2015
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0034
	Comments	The analysis was stratified by geographic region and metastasis classification (disease stage).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95% 0.49 to 0.87
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Final Analysis 28 August 2015
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0050
	Comments	The analysis was stratified by geographic region and metastasis classification (disease stage).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95% 0.55 to 0.90
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Percentage of Participants With an Objective Response
Description	An objective response was defined as a complete response or a partial ...
Description	An objective response was defined as a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors v1.1. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.
Time Frame	Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.


Arm/Group Title	Cobimetinib + Vemurafenib	Placebo + Vemurafenib
Arm/Group Description:	Participants received cobimetinib 6...	Participants received placebo orall...
Arm/Group Description:	Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed	247	248
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
Primary Analysis: 9 May 2014	67.60 (61.39 to 73.41)	44.80 (38.46 to 51.18)
Post hoc Efficacy Analysis: 16 January 2015	69.60 (63.50 to 75.30)	50.00 (43.60 to 56.40)
Extended 5-Year Analysis: 21 July 2019	69.60 (63.49 to 75.31)	49.60 (43.21 to 55.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Primary Analysis: 9 May 2014
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	22.85
	Confidence Interval	(2-Sided) 95% 14.13 to 31.58
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Post hoc Efficacy Analysis: 16 January 2015
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	19.6
	Confidence Interval	(2-Sided) 95% 11.0 to 28.3
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cobimetinib + Vemurafenib, Placebo + Vemurafenib
	Comments	Extended 5-Year Analysis: 21 July 2019
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	20.00
	Confidence Interval	(2-Sided) 95% 11.40 to 28.70
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Duration of Response
Description	Duration of response was defined as the time from first occurrence of ...
Description	Duration of response was defined as the time from first occurrence of a documented confirmed objective response until the time of disease progression, as determined by investigator review of tumor assessments using Response Evaluation Criteria in Solid Tumors v1.1 or death from any cause during the study. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Time Frame	Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received. Only participants with an objective response were included in the analysis.


Arm/Group Title		Cobimetinib + Vemurafenib	Placebo + Vemurafenib
Arm/Group Description:		Participants received cobimetinib 6...	Participants received placebo orall...
Arm/Group Description:		Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.	Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed		247	248
Median (95% Confidence Interval) Unit of Measure: Months
Primary Analysis: 9 May 2014	Number Analyzed	247 participants	248 participants
Primary Analysis: 9 May 2014		NA ^[1] (9.30 to NA)	7.29 ^[1] (5.78 to NA)
Extended 5-Year Analysis: 21 July 2019	Number Analyzed	172 participants	123 participants
Extended 5-Year Analysis: 21 July 2019		14.65 (12.90 to 19.30)	9.23 (7.50 to 12.90)

[1]

NA = not estimable, could not be calculated due to too few events.

Adverse Events

Time Frame	Adverse events were collected from the time of each participant's randomization into the study until their last visit until 28 days after the last dose of study drug and during extended 5-year efficacy and safety follow-up analyses (Safety data cut-off: July 2019; up to 7 years, 6 months).
Adverse Event Reporting Description	1 participant was randomized in Placebo + Vem but did not receive any study treatment, 1 participant randomized in Cobi+ Vem but did not receive any study treatment, two participants were randomized in Placebo + Vem but received the Cobi+Vem. All-cause Mortality is reported for the ITT population, SAEs and AEs are reported for the safety population. 1 participant died after 30 days from the last dose of treatment, after crossing over from the Placebo + Vem to the Cobi+Vem arm.

Arm/Group Title	Cobimetinib + Vemurafenib		Placebo + Vemurafenib
Arm/Group Description	Participants received cobimetinib 6...		Participants received placebo orall...
Arm/Group Description	Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.		Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
All-Cause Mortality
	Cobimetinib + Vemurafenib		Placebo + Vemurafenib
	Affected / at Risk (%)		Affected / at Risk (%)
Total	160/247 (64.78%)		164/248 (66.13%)
Serious Adverse Events Serious Adverse Events
	Cobimetinib + Vemurafenib		Placebo + Vemurafenib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/248 (42.34%)		71/245 (28.98%)
Blood and lymphatic system disorders
ANAEMIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Cardiac disorders
ACUTE CORONARY SYNDROME ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
ATRIAL FIBRILLATION ^† 1	4/248 (1.61%)	8	1/245 (0.41%)	1
CARDIAC ARREST ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
CARDIAC FAILURE ^† 1	1/248 (0.40%)	1	2/245 (0.82%)	2
CARDIAC TAMPONADE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
MYOCARDIAL INFARCTION ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
PERICARDIAL EFFUSION ^† 1	0/248 (0.00%)	0	4/245 (1.63%)	4
SUPRAVENTRICULAR TACHYCARDIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
TACHYCARDIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Endocrine disorders
HYPERTHYROIDISM ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Eye disorders
CHORIORETINOPATHY ^† 1	3/248 (1.21%)	5	0/245 (0.00%)	0
IRIDOCYCLITIS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
RETINAL DETACHMENT ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
RETINAL HAEMORRHAGE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
SEROUS RETINAL DETACHMENT ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
UVEITIS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Gastrointestinal disorders
ABDOMINAL PAIN ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
APHTHOUS ULCER ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
COLITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
CONSTIPATION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
DIARRHOEA ^† 1	3/248 (1.21%)	3	0/245 (0.00%)	0
DYSPHAGIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
GASTRIC ANTRAL VASCULAR ECTASIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GASTROINTESTINAL HAEMORRHAGE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GASTROINTESTINAL PAIN ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
GASTROOESOPHAGEAL REFLUX DISEASE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
INGUINAL HERNIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
INTESTINAL OBSTRUCTION ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
INTESTINAL PERFORATION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
MELAENA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
OBSTRUCTION GASTRIC ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
PANCREATITIS ^† 1	1/248 (0.40%)	1	2/245 (0.82%)	2
PERIODONTAL DISEASE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
RECTAL POLYP ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
SMALL INTESTINAL OBSTRUCTION ^† 1	3/248 (1.21%)	3	0/245 (0.00%)	0
VOMITING ^† 1	2/248 (0.81%)	2	1/245 (0.41%)	1
General disorders
ASTHENIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
CHEST PAIN ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
DEATH ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
FATIGUE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GAIT DISTURBANCE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
MALAISE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
PERIPHERAL SWELLING ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
PYREXIA ^† 1	7/248 (2.82%)	9	3/245 (1.22%)	3
Hepatobiliary disorders
CHOLECYSTITIS ^† 1	0/248 (0.00%)	0	2/245 (0.82%)	2
DRUG-INDUCED LIVER INJURY ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
HEPATITIS ACUTE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Immune system disorders
HYPERSENSITIVITY ^† 1	3/248 (1.21%)	3	0/245 (0.00%)	0
SARCOIDOSIS ^† 1	1/248 (0.40%)	2	0/245 (0.00%)	0
Infections and infestations
ABDOMINAL SEPSIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
ANAL ABSCESS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
ARTHRITIS BACTERIAL ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
CAMPYLOBACTER GASTROENTERITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
CELLULITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
CLOSTRIDIUM DIFFICILE COLITIS ^† 1	1/248 (0.40%)	2	0/245 (0.00%)	0
CLOSTRIDIUM DIFFICILE INFECTION ^† 1	1/248 (0.40%)	2	0/245 (0.00%)	0
DEVICE RELATED INFECTION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
DIVERTICULITIS ^† 1	1/248 (0.40%)	1	2/245 (0.82%)	2
ENTEROCOCCAL SEPSIS ^† 1	1/248 (0.40%)	2	0/245 (0.00%)	0
ERYSIPELAS ^† 1	1/248 (0.40%)	1	3/245 (1.22%)	4
GASTROENTERITIS ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
GASTROENTERITIS CLOSTRIDIAL ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
GASTROENTERITIS VIRAL ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
GASTROINTESTINAL BACTERIAL INFECTION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GENITOURINARY TRACT INFECTION ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
GROIN ABSCESS ^† 1	1/248 (0.40%)	2	0/245 (0.00%)	0
INFECTION ^† 1	1/248 (0.40%)	2	0/245 (0.00%)	0
PNEUMONIA ^† 1	6/248 (2.42%)	6	3/245 (1.22%)	3
SEPSIS ^† 1	1/248 (0.40%)	1	2/245 (0.82%)	2
SEPTIC SHOCK ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
TONSILLITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
TUBERCULOSIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
URINARY TRACT INFECTION ^† 1	2/248 (0.81%)	2	1/245 (0.41%)	1
VULVAL CELLULITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
WOUND INFECTION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Injury, poisoning and procedural complications
FACIAL BONES FRACTURE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
FALL ^† 1	2/248 (0.81%)	4	0/245 (0.00%)	0
FEMORAL NECK FRACTURE ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
FRACTURE DISPLACEMENT ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
OVERDOSE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
RIB FRACTURE ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
SKIN LACERATION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
THORACIC VERTEBRAL FRACTURE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
TRAUMATIC HAEMATOMA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
UPPER LIMB FRACTURE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED ^† 1	4/248 (1.61%)	4	2/245 (0.82%)	2
ASPARTATE AMINOTRANSFERASE INCREASED ^† 1	3/248 (1.21%)	3	2/245 (0.82%)	2
BLOOD ALKALINE PHOSPHATASE INCREASED ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
BLOOD CREATINE PHOSPHOKINASE INCREASED ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
BLOOD CREATININE INCREASED ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
EJECTION FRACTION DECREASED ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
ELECTROCARDIOGRAM QT PROLONGED ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
ELECTROCARDIOGRAM T WAVE ABNORMAL ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED ^† 1	3/248 (1.21%)	3	1/245 (0.41%)	1
HAEMOGLOBIN DECREASED ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
LIPASE INCREASED ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
LIVER FUNCTION TEST INCREASED ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
Metabolism and nutrition disorders
DEHYDRATION ^† 1	6/248 (2.42%)	6	0/245 (0.00%)	0
DIABETES MELLITUS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
HYPERNATRAEMIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
HYPOKALAEMIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
HYPONATRAEMIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
TYPE 2 DIABETES MELLITUS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
BACK PAIN ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
BURSITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
MUSCULAR WEAKNESS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
MUSCULOSKELETAL CHEST PAIN ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
MUSCULOSKELETAL PAIN ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
MYALGIA ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
PATHOLOGICAL FRACTURE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
POLYARTHRITIS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
RHABDOMYOLYSIS ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACANTHOMA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
ADENOCARCINOMA OF COLON ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
BENIGN NEOPLASM ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
ENDOMETRIAL ADENOCARCINOMA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GASTROINTESTINAL TRACT ADENOMA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
KAPOSI'S SARCOMA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
KERATOACANTHOMA ^† 1	0/248 (0.00%)	0	4/245 (1.63%)	4
LUNG ADENOCARCINOMA ^† 1	0/248 (0.00%)	0	2/245 (0.82%)	3
MALIGNANT MELANOMA IN SITU ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
MUCINOUS BREAST CARCINOMA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
PAPILLOMA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
SQUAMOUS CELL CARCINOMA OF SKIN ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
TRANSITIONAL CELL CARCINOMA ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
TUMOUR HAEMORRHAGE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
TUMOUR PAIN ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Nervous system disorders
CEREBRAL HAEMORRHAGE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
CEREBROVASCULAR ACCIDENT ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
COMA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
DIZZINESS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
DYSARTHRIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
DYSGEUSIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
FACIAL PARALYSIS ^† 1	2/248 (0.81%)	2	1/245 (0.41%)	1
FACIAL PARESIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
GENERALISED TONIC-CLONIC SEIZURE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
HAEMORRHAGIC STROKE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
HEADACHE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
HEMIPARESIS ^† 1	2/248 (0.81%)	2	0/245 (0.00%)	0
HYDROCEPHALUS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
ISCHAEMIC STROKE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
MYASTHENIA GRAVIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
PARAESTHESIA ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
POLYNEUROPATHY ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
SEIZURE ^† 1	3/248 (1.21%)	3	0/245 (0.00%)	0
SUBARACHNOID HAEMORRHAGE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
SYNCOPE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Psychiatric disorders
MANIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY ^† 1	3/248 (1.21%)	3	2/245 (0.82%)	3
DIABETIC NEPHROPATHY ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
RENAL COLIC ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
URETEROLITHIASIS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Reproductive system and breast disorders
CERVICAL POLYP ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Respiratory, thoracic and mediastinal disorders
ATELECTASIS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
DYSPNOEA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
INTERSTITIAL LUNG DISEASE ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
PLEURAL EFFUSION ^† 1	0/248 (0.00%)	0	3/245 (1.22%)	3
PNEUMONITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
PULMONARY EMBOLISM ^† 1	3/248 (1.21%)	3	1/245 (0.41%)	1
PULMONARY HAEMORRHAGE ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
Skin and subcutaneous tissue disorders
DERMATITIS EXFOLIATIVE GENERALISED ^† 1	0/248 (0.00%)	0	2/245 (0.82%)	2
DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS ^† 1	1/248 (0.40%)	1	1/245 (0.41%)	1
ERYTHEMA MULTIFORME ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
ERYTHEMA NODOSUM ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
HYPERKERATOSIS ^† 1	0/248 (0.00%)	0	1/245 (0.41%)	1
PANNICULITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
PHOTOSENSITIVITY REACTION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
RASH ^† 1	4/248 (1.61%)	4	2/245 (0.82%)	2
RASH GENERALISED ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
RASH MACULAR ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
RASH MACULO-PAPULAR ^† 1	3/248 (1.21%)	3	2/245 (0.82%)	2
RASH MORBILLIFORM ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
URTICARIA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
Vascular disorders
HYPERTENSION ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
HYPERTENSIVE CRISIS ^† 1	2/248 (0.81%)	2	1/245 (0.41%)	1
SUBGALEAL HAEMATOMA ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
VASCULITIS ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
VENOUS THROMBOSIS LIMB ^† 1	1/248 (0.40%)	1	0/245 (0.00%)	0
1 Term from vocabulary, MedDRA (22.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0.05%
	Cobimetinib + Vemurafenib		Placebo + Vemurafenib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	239/248 (96.37%)		236/245 (96.33%)
Blood and lymphatic system disorders
ANAEMIA ^† 1	51/248 (20.56%)	76	21/245 (8.57%)	26
Eye disorders
CHORIORETINOPATHY ^† 1	30/248 (12.10%)	36	4/245 (1.63%)	9
VISION BLURRED ^† 1	32/248 (12.90%)	37	8/245 (3.27%)	9
Gastrointestinal disorders
ABDOMINAL PAIN ^† 1	30/248 (12.10%)	37	20/245 (8.16%)	23
ABDOMINAL PAIN UPPER ^† 1	15/248 (6.05%)	17	18/245 (7.35%)	21
CONSTIPATION ^† 1	27/248 (10.89%)	37	29/245 (11.84%)	31
DIARRHOEA ^† 1	151/248 (60.89%)	311	84/245 (34.29%)	162
DYSPEPSIA ^† 1	19/248 (7.66%)	22	13/245 (5.31%)	15
NAUSEA ^† 1	108/248 (43.55%)	184	67/245 (27.35%)	83
STOMATITIS ^† 1	17/248 (6.85%)	27	3/245 (1.22%)	3
VOMITING ^† 1	69/248 (27.82%)	108	33/245 (13.47%)	42
General disorders
ASTHENIA ^† 1	51/248 (20.56%)	96	43/245 (17.55%)	50
CHILLS ^† 1	25/248 (10.08%)	28	14/245 (5.71%)	17
FATIGUE ^† 1	93/248 (37.50%)	137	83/245 (33.88%)	99
OEDEMA PERIPHERAL ^† 1	38/248 (15.32%)	49	28/245 (11.43%)	32
PYREXIA ^† 1	77/248 (31.05%)	130	60/245 (24.49%)	77
Infections and infestations
CONJUNCTIVITIS ^† 1	18/248 (7.26%)	19	8/245 (3.27%)	10
FOLLICULITIS ^† 1	19/248 (7.66%)	22	12/245 (4.90%)	15
NASOPHARYNGITIS ^† 1	23/248 (9.27%)	29	18/245 (7.35%)	21
UPPER RESPIRATORY TRACT INFECTION ^† 1	14/248 (5.65%)	18	11/245 (4.49%)	15
URINARY TRACT INFECTION ^† 1	17/248 (6.85%)	25	11/245 (4.49%)	13
Injury, poisoning and procedural complications
SUNBURN ^† 1	37/248 (14.92%)	60	45/245 (18.37%)	68
Investigations
ALANINE AMINOTRANSFERASE INCREASED ^† 1	65/248 (26.21%)	94	44/245 (17.96%)	48
ASPARTATE AMINOTRANSFERASE INCREASED ^† 1	64/248 (25.81%)	87	29/245 (11.84%)	30
BLOOD ALKALINE PHOSPHATASE INCREASED ^† 1	46/248 (18.55%)	67	26/245 (10.61%)	30
BLOOD BILIRUBIN INCREASED ^† 1	20/248 (8.06%)	29	17/245 (6.94%)	22
BLOOD CHOLESTEROL INCREASED ^† 1	16/248 (6.45%)	19	10/245 (4.08%)	10
BLOOD CREATINE PHOSPHOKINASE INCREASED ^† 1	90/248 (36.29%)	171	10/245 (4.08%)	13
BLOOD CREATININE INCREASED ^† 1	45/248 (18.15%)	59	20/245 (8.16%)	25
BLOOD LACTATE DEHYDROGENASE INCREASED ^† 1	15/248 (6.05%)	30	8/245 (3.27%)	8
EJECTION FRACTION DECREASED ^† 1	31/248 (12.50%)	46	12/245 (4.90%)	13
ELECTROCARDIOGRAM QT PROLONGED ^† 1	12/248 (4.84%)	15	13/245 (5.31%)	19
GAMMA-GLUTAMYLTRANSFERASE INCREASED ^† 1	57/248 (22.98%)	82	45/245 (18.37%)	61
WEIGHT DECREASED ^† 1	18/248 (7.26%)	20	14/245 (5.71%)	17
Metabolism and nutrition disorders
DECREASED APPETITE ^† 1	55/248 (22.18%)	75	50/245 (20.41%)	55
HYPONATRAEMIA ^† 1	13/248 (5.24%)	19	3/245 (1.22%)	3
Musculoskeletal and connective tissue disorders
ARTHRALGIA ^† 1	96/248 (38.71%)	172	105/245 (42.86%)	179
BACK PAIN ^† 1	21/248 (8.47%)	30	15/245 (6.12%)	15
MUSCULOSKELETAL PAIN ^† 1	17/248 (6.85%)	18	16/245 (6.53%)	19
MYALGIA ^† 1	41/248 (16.53%)	53	33/245 (13.47%)	37
PAIN IN EXTREMITY ^† 1	32/248 (12.90%)	51	40/245 (16.33%)	54
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA ^† 1	16/248 (6.45%)	33	6/245 (2.45%)	6
KERATOACANTHOMA ^† 1	5/248 (2.02%)	6	20/245 (8.16%)	26
MELANOCYTIC NAEVUS ^† 1	5/248 (2.02%)	5	17/245 (6.94%)	26
SEBORRHOEIC KERATOSIS ^† 1	15/248 (6.05%)	15	21/245 (8.57%)	24
SKIN PAPILLOMA ^† 1	18/248 (7.26%)	26	30/245 (12.24%)	36
SQUAMOUS CELL CARCINOMA OF SKIN ^† 1	10/248 (4.03%)	25	33/245 (13.47%)	66
Nervous system disorders
DIZZINESS ^† 1	18/248 (7.26%)	18	7/245 (2.86%)	8
DYSGEUSIA ^† 1	27/248 (10.89%)	29	16/245 (6.53%)	17
HEADACHE ^† 1	50/248 (20.16%)	76	41/245 (16.73%)	50
Psychiatric disorders
ANXIETY ^† 1	16/248 (6.45%)	18	11/245 (4.49%)	12
DEPRESSION ^† 1	15/248 (6.05%)	17	11/245 (4.49%)	11
INSOMNIA ^† 1	19/248 (7.66%)	24	27/245 (11.02%)	31
Respiratory, thoracic and mediastinal disorders
COUGH ^† 1	28/248 (11.29%)	36	32/245 (13.06%)	37
DYSPNOEA ^† 1	19/248 (7.66%)	26	19/245 (7.76%)	23
OROPHARYNGEAL PAIN ^† 1	19/248 (7.66%)	20	22/245 (8.98%)	28
Skin and subcutaneous tissue disorders
ACTINIC KERATOSIS ^† 1	13/248 (5.24%)	32	27/245 (11.02%)	31
ALOPECIA ^† 1	42/248 (16.94%)	44	75/245 (30.61%)	78
DERMATITIS ACNEIFORM ^† 1	37/248 (14.92%)	47	22/245 (8.98%)	26
DRY SKIN ^† 1	37/248 (14.92%)	40	42/245 (17.14%)	46
ERYTHEMA ^† 1	32/248 (12.90%)	56	36/245 (14.69%)	57
HYPERKERATOSIS ^† 1	31/248 (12.50%)	39	74/245 (30.20%)	130
KERATOSIS PILARIS ^† 1	13/248 (5.24%)	14	26/245 (10.61%)	30
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME ^† 1	18/248 (7.26%)	23	9/245 (3.67%)	10
PHOTOSENSITIVITY REACTION ^† 1	86/248 (34.68%)	119	48/245 (19.59%)	58
PRURITUS ^† 1	51/248 (20.56%)	85	48/245 (19.59%)	54
RASH ^† 1	101/248 (40.73%)	158	97/245 (39.59%)	121
RASH MACULO-PAPULAR ^† 1	37/248 (14.92%)	61	37/245 (15.10%)	47
SOLAR DERMATITIS ^† 1	18/248 (7.26%)	34	14/245 (5.71%)	23
Vascular disorders
HYPERTENSION ^† 1	50/248 (20.16%)	60	30/245 (12.24%)	33
1 Term from vocabulary, MedDRA (22.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

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Name/Title:	Medical Communications
Organization:	Hoffmann-La Roche
Phone:	800 821-8590

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

Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.

Ascierto PA, Dreno B, Larkin J, Ribas A, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Atkinson V, Dutriaux C, Garbe C, Hsu J, Jones S, Li H, McKenna E, Voulgari A, McArthur GA. 5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation-Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study. Clin Cancer Res. 2021 Oct 1;27(19):5225-5235. doi: 10.1158/1078-0432.CCR-21-0809.

Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.

de la Cruz-Merino L, Di Guardo L, Grob JJ, Venosa A, Larkin J, McArthur GA, Ribas A, Ascierto PA, Evans JTR, Gomez-Escobar A, Barteselli G, Eng S, Hsu JJ, Uyei A, Dreno B. Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF-mutated melanoma treated in the randomized coBRIM study. J Transl Med. 2017 Jun 24;15(1):146. doi: 10.1186/s12967-017-1246-0.

Dreno B, Ribas A, Larkin J, Ascierto PA, Hauschild A, Thomas L, Grob JJ, Koralek DO, Rooney I, Hsu JJ, McKenna EF, McArthur GA. Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study. Ann Oncol. 2017 May 1;28(5):1137-1144. doi: 10.1093/annonc/mdx040.

Ascierto PA, McArthur GA, Dreno B, Atkinson V, Liszkay G, Di Giacomo AM, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Yan Y, Wongchenko M, Chang I, Hsu JJ, Koralek DO, Rooney I, Ribas A, Larkin J. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1248-60. doi: 10.1016/S1470-2045(16)30122-X. Epub 2016 Jul 30.

Larkin J, Ascierto PA, Dreno B, Atkinson V, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014 Nov 13;371(20):1867-76. doi: 10.1056/NEJMoa1408868. Epub 2014 Sep 29.

Layout table for additonal information

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01689519
Other Study ID Numbers:	GO28141 2012-003008-11 ( EudraCT Number )
First Submitted:	September 18, 2012
First Posted:	September 21, 2012
Results First Submitted:	July 1, 2015
Results First Posted:	October 30, 2015
Last Update Posted:	May 2, 2022

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