Trial Outcomes & Findings for A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases (NCT NCT01378975)

Last Updated: 2025-06-25

Results Overview

BORR assessed by IRC is defined as percentage of participants who were responders \[with best overall response (BOR) documented as confirmed complete response (CR) or partial response (PR)\]. The RECIST v1.1 criteria modified for independent review of body and brain lesions was based on current radiology practices. The modifications to RECIST v1.1 included allowing target lesions in the brain to be \>=5 mm by contrast-enhanced magnetic resonance imaging scan (in traditional RECIST v1.1 this is \>=10 mm), allowing up to 5 target lesions in the brain (in traditional RECIST v1.1 only 2 target lesions), and examining the lesions within the brain and outside the brain separately for analytical purposes. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm), PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

146 participants

Primary outcome timeframe

Baseline up to the disease progression or death from any cause (approximately 4 years)

Results posted on

2025-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1: Previously Untreated Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Study STARTED	90	56
Overall Study COMPLETED	4	6
Overall Study NOT COMPLETED	86	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Previously Untreated Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Study Death	77	46
Overall Study Investigator Request	1	0
Overall Study Lost to Follow-up	4	1
Overall Study Withdrew Consent	4	3

Baseline Characteristics

A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Total n=146 Participants Total of all reporting groups
Age, Continuous	55.7 years STANDARD_DEVIATION 12.73 • n=5 Participants	52.7 years STANDARD_DEVIATION 13.85 • n=7 Participants	54.5 years STANDARD_DEVIATION 13.20 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	22 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	34 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The intent to treat (ITT) population included all participants who were enrolled in the study.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Best Overall Response Rate (BORR) Within Brain of Previously Untreated Participants (Assessed by Independent Review Committee [IRC] Using Modified Response Evaluation Criteria in Solid Tumors [RECIST])	17.8 percentage of participants Interval 10.5 to 27.3	—

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study.

Percentage of participants who were responders with BOR documented as confirmed CR or PR, stable disease (SD), progressive disease (PD). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1 Complete Response	2.2 percentage of participants	0.0 percentage of participants
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1 Partial Response	15.6 percentage of participants	17.9 percentage of participants
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1 Stable Disease	43.3 percentage of participants	41.1 percentage of participants
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1 Progressive Disease	32.2 percentage of participants	33.9 percentage of participants
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1 Unevaluable	6.7 percentage of participants	7.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study.

BORR within brain assessed by IRC is defined as percentage of participants who were responders (with BOR documented as confirmed CR or PR). According to RECIST v1.1 criteria modified for brain metastases, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=56 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1	17.9 percentage of participants Interval 8.9 to 30.4	—

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study. Here, number participants analyzed is the total number of participants who had measurable disease outside brain at baseline.

BORR outside of brain assessed by IRC is defined as percentage of participants who were responders (with BOR documented as confirmed CR or PR). According to RECIST v1.1 criteria modified for brain metastases, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=79 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=40 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Best Overall Response Rate Outside the Brain (Assessed by IRC)	32.9 percentage of participants Interval 22.7 to 44.4	22.5 percentage of participants Interval 10.8 to 38.5

SECONDARY outcome

Timeframe: Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years)

Population: The ITT population included all participants who were enrolled in the study. Here, 'n' indicates number of participants who were responders within brain or outside brain assessed by investigator or IRC.

Duration of response was defined as the time interval between the date of the earliest qualifying response and the earliest date of PD or death from any cause. For participants who were alive without progression following the qualifying response, DOR were censored on the date of last available tumor assessment on or before the data cutoff date.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=26 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=13 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Duration of Response (DOR) (Assessed by Investigator and IRC) Investigator: DOR (Within Brain) (n=26, 13)	4.67 months Interval 2.66 to 24.21	6.64 months Interval 1.87 to 21.98
Duration of Response (DOR) (Assessed by Investigator and IRC) Investigator: DOR (Outside Brain) (n=25, 11)	5.55 months Interval 1.84 to 25.63	10.74 months Interval 1.84 to 23.1
Duration of Response (DOR) (Assessed by Investigator and IRC) IRC: DOR (Within Brain) (n=16, 10)	4.60 months Interval 2.66 to 29.9	6.64 months Interval 0.95 to 18.4
Duration of Response (DOR) (Assessed by Investigator and IRC) IRC: DOR (Outside Brain) (n=26, 9)	7.72 months Interval 1.84 to 21.55	11.07 months Interval 1.84 to 23.1

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study.

Progression-free survival was defined as the time between enrollment on Day 1 and the date of first radiographically documented progressive disease (within or outside the brain), clinical progressive disease, as assessed by the investigator or death whichever occurred first.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)	3.65 months Interval 0.3 to 33.35	3.71 months Interval 0.26 to 27.37

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study.

Progression-free survival was defined as the time between enrollment on Day 1 and the date of first radiographically documented progressive disease (within brain), clinical progressive disease, as assessed by the investigator or death whichever occurred first.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )	3.68 months Interval 0.36 to 33.35	4.04 months Interval 0.26 to 27.37

SECONDARY outcome

Timeframe: Date of first treatment and the earliest date of documentation of new brain lesions (approximately up to 4 years)

Population: The ITT population included all participants who were enrolled in the study. Here, number of participants analyzed is the participants who were responders.

Time to development of new lesions within the brain was defined as the interval between the date of first treatment and the earliest date of documentation of new brain lesions. Participants who were known to be free of new lesions were censored on the date of last tumor assessment.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=26 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=13 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Time to Development of New Brain Metastases in Responders	14.92 months Interval 3.48 to 33.35	14.52 months Interval 2.79 to 27.37

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study.

Overall survival was defined as time between enrollment on Day 1 and date of death, irrespective of the cause of death. Participants for whom no death was captured on the clinical database were censored at the latest date they were known to be alive prior to or on the cutoff date.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Survival	8.87 months Interval 0.59 to 34.53	9.63 months Interval 0.66 to 34.3

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study. Here, 'n' indicates the number participants who were evaluable for within brain assessment and who had measurable disease outside brain at baseline for outside brain assessment.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Complete Response (Within Brain) (n=90, 56)	2.2 percentage of participants	0.0 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Partial Response (Within Brain) (n=90, 56)	26.7 percentage of participants	23.2 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Stable Disease (Within Brain) (n=90, 56)	40.0 percentage of participants	53.6 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Progressive Disease (Within Brain) (n=90, 56)	27.8 percentage of participants	19.6 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Unevaluable (Within Brain) (n=90, 56)	3.3 percentage of participants	3.6 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Complete Response (Outside Brain) (n=79, 40)	0.0 percentage of participants	5.0 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Partial Response (Outside Brain) (n=79, 40)	31.6 percentage of participants	22.5 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Stable Disease (Outside Brain) (n=79, 40)	49.4 percentage of participants	52.5 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Progressive Disease (Outside Brain) (n=79, 40)	11.4 percentage of participants	15.0 percentage of participants
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator) Unevaluable (Outside Brain) (n=79, 40)	7.6 percentage of participants	5.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to the disease progression or death from any cause (approximately 4 years)

Population: The ITT population included all participants who were enrolled in the study.

Percentage of participants who were responders (with best overall response (BOR) documented as confirmed complete response \[CR\] or partial response \[PR\]) were reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator)	18.9 percentage of participants Interval 11.4 to 28.5	17.9 percentage of participants Interval 8.9 to 30.4

SECONDARY outcome

Timeframe: From signing of informed consent form up to 28 days after the last dose of study drug (approximately up to 4 years)

Population: The safety population included all participants who received at least one dose of study medication.

An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug.

Outcome measures

Outcome measures
Measure	Cohort 1: Previously Untreated Participants n=90 Participants Participants who had not received previous treatment for brain metastases \[i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases\] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.	Cohort 2: Previously Treated Participants n=56 Participants Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant's safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Percentage of Participants With Adverse Events (AE)	97.8 percentage of participants	94.6 percentage of participants

Adverse Events

Cohort 1: Previously Untreated Participants

Serious events: 37 serious events

Other events: 85 other events

Deaths: 77 deaths

Cohort 2: Previously Treated Participants

Serious events: 27 serious events

Other events: 53 other events

Deaths: 46 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER