Trial Outcomes & Findings for Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) (NCT NCT01400451)

Last Updated: 2015-01-01

Results Overview

AEs graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Lead In Period: between the first vemurafenib dose and the day prior to the first ipilimumab dose.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

From first vemurafenib dose to day prior to first ipilimumab dose (28 days); Patients who never progressed from Lead-in to combination treatment (720 mg Alone): first dose to last dose + 90 days (approximately 2 years)

Results posted on

2015-01-01

Participant Flow

Study started Nov 2011; Primary Endpoint April 2013; Completed safety follow-up December 2013. Dose-limiting toxicities observed early in dose escalation (Phase I) part of the study. The combination of drugs was not well tolerated, and a maximum tolerable dose was not attained so the study was closed to enrollment and Phase II part was not started.

18 participants enrolled; 12 treated with study drug and 6 participants were not treated because they no longer met study criteria. Two of the 12 only received vemurafenib while the other 10 received the combination of vemurafenib and ipilimumab.

Participant milestones

Participant milestones
Measure	3 mg/kg Ipilimumab + 960 mg Vemurafenib Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily throughout combination treatment.	3 mg/kg Ipilimumab + 720 mg Vemurafenib Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily throughout combination treatment.	720 mg Vemurafenib These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Note: the dose of vemurafenib could be escalated from 720 mg to 960 mg, at the investigator's discretion.
28 Day Lead In With Vemurafenib Alone STARTED	6	4	2
28 Day Lead In With Vemurafenib Alone COMPLETED	6	4	2
28 Day Lead In With Vemurafenib Alone NOT COMPLETED	0	0	0
Combination Treatment (or Intended) STARTED	6	4	2
Combination Treatment (or Intended) COMPLETED	0	0	0
Combination Treatment (or Intended) NOT COMPLETED	6	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	3 mg/kg Ipilimumab + 960 mg Vemurafenib Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily throughout combination treatment.	3 mg/kg Ipilimumab + 720 mg Vemurafenib Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily throughout combination treatment.	720 mg Vemurafenib These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Note: the dose of vemurafenib could be escalated from 720 mg to 960 mg, at the investigator's discretion.
Combination Treatment (or Intended) Withdrawal by Subject	2	1	1
Combination Treatment (or Intended) Drug Toxicity	0	1	0
Combination Treatment (or Intended) Adverse Event	1	0	0
Combination Treatment (or Intended) Disease Progression	3	1	1
Combination Treatment (or Intended) Dose-limiting toxicity	0	1	0

Baseline Characteristics

Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	3 mg/kg Ipilimumab + 960 mg Vemurafenib n=6 Participants Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1, plus 960 mg vemurafenib orally twice daily throughout combination treatment.	3 mg/kg Ipilimumab + 720 mg Vemurafenib n=4 Participants Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily throughout combination treatment.	720 mg Vemurafenib n=2 Participants These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=93 Participants	4 Participants n=4 Participants	1 Participants n=27 Participants	8 Participants n=483 Participants
Age, Categorical >=65 years	3 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	4 Participants n=483 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	11 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment United States	6 participants n=93 Participants	4 participants n=4 Participants	2 participants n=27 Participants	12 participants n=483 Participants

PRIMARY outcome

Timeframe: From first vemurafenib dose to day prior to first ipilimumab dose (28 days); Patients who never progressed from Lead-in to combination treatment (720 mg Alone): first dose to last dose + 90 days (approximately 2 years)

Population: All participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	960 mg Vemurafenib Lead in Period n=6 Participants Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	720 mg Vemurafenib Lead in Period n=4 Participants Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	720 mg Vemurafenib Alone n=2 Participants These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Events from first day of vemurafenib to last day of treatment + 90 days, up to date of data cut off for Primary Endpoint.
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 3 SAEs	2 participants	1 participants	1 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 4 SAEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 5 SAEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Drug Related Grade 3 SAEs	2 participants	1 participants	1 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Drug Related Grade 4 SAEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone AEs Leading to Study Drug Discontinuation	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 1 irAEs	2 participants	3 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 2 irAEs	1 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 3 irAEs	2 participants	0 participants	1 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 4 irAEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 1 AEs	0 participants	1 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 2 AEs	2 participants	2 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 3 AEs	4 participants	1 participants	2 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 4 AEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Grade 5 AEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Drug Related Grade 1 AEs	1 participants	1 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Drug Related Grade 2 AEs	2 participants	2 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Drug Related Grade 3 AEs	3 participants	1 participants	2 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Drug Related Grade 4 AEs	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Deaths	0 participants	0 participants	0 participants
During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone Deaths due to disease progression	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Combination drugs: Day 1 to last dose of drug + 90 days (approximately 2 years)

Population: All participants who received at least one dose of study drug.

AEs graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. AEs: onset on or after ipilimumab start and within 90 days of last dose. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Day 1=first dose of ipilimumab.

Outcome measures

Outcome measures
Measure	960 mg Vemurafenib Lead in Period n=6 Participants Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	720 mg Vemurafenib Lead in Period n=4 Participants Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	720 mg Vemurafenib Alone These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Events from first day of vemurafenib to last day of treatment + 90 days, up to date of data cut off for Primary Endpoint.
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Deaths	4 participants	1 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Deaths due to disease progression	4 participants	1 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 3 SAEs	3 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 4 SAEs	0 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 5 SAEs	2 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Drug Related Grade 3 SAEs	5 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Drug Related Grade 4 SAEs	0 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib AEs Leading to Study Drug Discontinuation	2 participants	1 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 1 irAEs	1 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 2 irAEs	1 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 3 irAEs	4 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 4 irAEs	0 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 1 AEs	0 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 2 AEs	1 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 3 AEs	3 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 4 AEs	0 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Grade 5 AEs	2 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Drug Related Grade 1 AEs	0 participants	0 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Drug Related Grade 2 AEs	1 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Drug Related Grade 3 AEs	5 participants	2 participants	—
During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib Drug Related Grade 4 AEs	0 participants	0 participants	—

PRIMARY outcome

Timeframe: Day 1 to last dose of drug + 90 (approximately 2 years)

Population: All participants who received at least one dose of concurrent study drugs.

DLT defined as a \>= Grade 3 drug-related AE during induction with ipilimumab in combination with vemurafenib excluding: Grade 3 AE of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor); Grade 3 cutaneous squamous cell carcinoma; Grade 3 photosensitivity that resolved to a Grade 1 or baseline within 15 days; Grade 3 immune-mediated events of the skin (rash, pruritis) or endocrine systems (hypothyroidism, hyperthyroidism, hypopituitarism, adrenal insufficiency, hypogonadism and cushingoid) that resolved to a Grade 1 or baseline within 28 days; a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Hepatic=elevated aspartate aminotransferase and alanine aminotransferase. Maximum tolerable dose (MTD) was defined as the maximum dose of combination treatment that could be given to 6 subjects such that no more than 2 subjects experience DLT. Day 1=first day of concurrent therapy with ipilimumab and vemurafenib.

Outcome measures

Outcome measures
Measure	960 mg Vemurafenib Lead in Period n=4 Participants Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	720 mg Vemurafenib Lead in Period n=2 Participants Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	720 mg Vemurafenib Alone These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Events from first day of vemurafenib to last day of treatment + 90 days, up to date of data cut off for Primary Endpoint.
Number of Participants With Hepatic Dose Limiting Toxicities (DLT) in Participants Treated With Concurrent Ipilimumab and Vemurafenib	4 participants	2 participants	—

Adverse Events

Lead-In Period 960 mg Vemurafenib

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Lead-In Period 720 mg Vemurafenib

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Lead- In Period 720 mg Vemurafenib Alone

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

3 mg/kg Ipilimumab + 960 mg Vemurafenib

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

3 mg/kg Ipilimumab + 720 mg Vemurafenib

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lead-In Period 960 mg Vemurafenib n=6 participants at risk Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	Lead-In Period 720 mg Vemurafenib n=4 participants at risk Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	Lead- In Period 720 mg Vemurafenib Alone n=2 participants at risk These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.	3 mg/kg Ipilimumab + 960 mg Vemurafenib n=6 participants at risk 3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily and continuing during combination treatment.	3 mg/kg Ipilimumab + 720 mg Vemurafenib n=4 participants at risk 3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily continuing during combination treatment.
Infections and infestations Cytomegalovirus enteritis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Psychiatric disorders Confusional state	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Rash pustular	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Vascular disorders Temporal arteritis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Alanine aminotransferase increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	66.7% 4/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Liver function test abnormal	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.

Other adverse events

Other adverse events
Measure	Lead-In Period 960 mg Vemurafenib n=6 participants at risk Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	Lead-In Period 720 mg Vemurafenib n=4 participants at risk Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13). Events between the first vemurafenib dose and the day prior to the first ipilimumab dose.	Lead- In Period 720 mg Vemurafenib Alone n=2 participants at risk These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the DLTs were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.	3 mg/kg Ipilimumab + 960 mg Vemurafenib n=6 participants at risk 3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily and continuing during combination treatment.	3 mg/kg Ipilimumab + 720 mg Vemurafenib n=4 participants at risk 3 mg/kg ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily continuing during combination treatment.
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Psychiatric disorders Adjustment disorder	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Candidiasis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Renal and urinary disorders Chromaturia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	75.0% 3/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Eye swelling	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Flatulence	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Keratosis pilaris	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Lymphocyte count decreased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Secretion discharge	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Blood creatinine increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Chills	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Injury, poisoning and procedural complications Contrast media reaction	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Metabolism and nutrition disorders Decreased appetite	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Dizziness	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Electrocardiogram QT prolonged	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Lacrimation increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Palmar erythema	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash erythematous	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Injury, poisoning and procedural complications Sunburn	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Blood bilirubin increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Conjunctivitis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Lipase increased	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Nausea	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	75.0% 3/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Oedema peripheral	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash papular	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Xerosis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Constipation	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Dysgeusia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Hyperkeratosis	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Metabolism and nutrition disorders Hypokalaemia	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Influenza	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Temperature intolerance	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Weight decreased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Blood alkaline phosphatase increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Conjunctival hyperaemia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Dry eye	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Renal and urinary disorders Dysuria	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Episcleritis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Fatigue	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	75.0% 3/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Endocrine disorders Hypothyroidism	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	66.7% 4/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	75.0% 3/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Eye disorders Visual impairment	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Vomiting	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Coordination abnormal	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Faeces pale	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Headache	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	75.0% 3/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Hypogeusia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Influenza like illness	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Psychiatric disorders Insomnia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Pharyngitis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Reproductive system and breast disorders Vulvovaginal discomfort	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Asthenia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Nasopharyngitis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 1/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Photosensitivity reaction	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	100.0% 2/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
General disorders Pyrexia	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Rash pustular	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Blood and lymphatic system disorders Thrombocytopenia	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Alanine aminotransferase increased	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	33.3% 2/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Infections and infestations Bronchitis	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Lacunar infarction	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Investigations Liver function test abnormal	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Nervous system disorders Neuropathy peripheral	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	25.0% 1/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 3/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	50.0% 2/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.
Skin and subcutaneous tissue disorders Rash generalised	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/2 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	16.7% 1/6 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.	0.00% 0/4 • From the first vemurafenib dose in the Lead In Period to the last dose of combination drugs in the Treatment Period + 90 days, up to last patient, last visit, approximately 2 years. Final safety follow-up was 23 December 2013.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
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