Metastatic Melanoma
Conditions
Brief summary
This study will evaluate the efficacy and safety of cobimetinib plus atezolizumab in participants with BRAFV600 wild-type melanoma with central nervous system (CNS) metastases and of cobimetinib plus atezolizumab and vemurafenib in BRAFV600 mutation-positive melanoma patients with CNS metastases.
Interventions
DRUGCobimetinib
60 mg (three tablets of 20 mg each) orally (PO) once a day (QD) on Days 1-21 of each 28-day cycle.
DRUGAtezolizumab
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle. Only for cohort 2, no dose of atezolizumab will be given during the run-in period (cycle 1).
DRUGVemurafenib
Participants will receive vemurafenib 960 mg (four 240 mg tablets) orally (PO) twice daily (BID) on days 1-21 of the run-in period (cycle 1); thereafter, they will receive vemurafenib 720 mg dose (three 240 mg tablets) PO BID on days 22-28 of cycle 1 and on days 1-28 of all subsequent cycles.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Disease-specific inclusion criteria: * Histologically confirmed melanoma with radiologically confirmed brain metastases * Documented BRAFV600 mutation status of melanoma tumour tissue using a validated genetic test. * Measurable brain metastases * Prior systemic therapy for metastatic melanoma is allowed with exceptions as detailed in the
Exclusion criteria
* Prior SRT or surgical therapy of ≤ 10 brain metastases is allowed but prior WBRT is not allowed * Adverse effects of all prior systemic or local treatment must have either returned to baseline or become stable and manageable prior to initiation of study treatment. General inclusion criteria: * Age ≥18 years * Able to comply with the study protocol, in the investigator's judgment * ECOG Performance Status ≤ 2 * Life expectancy of \> 3 months * Willing and able to complete health and quality of life questionnaires required by the protocol * Adequate hematologic and end-organ function * Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective forms of contraception during the course of this study and for at least six months after completion of study therapy. * Male patients must agree to refrain from donating sperm for at least six months after the last dose of cobimetinib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial Objective Response Rate (ORR) | Baseline up to cut of date (approximately 2.5 years) | Intracranial ORR is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) in their intracranial disease based on two consecutive assessments \>= 4 weeks apart. Disease status for this endpoint will be determined by an Independent Review Committee (IRC) in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) with modified measurability definition for intracranial lesions (\>= 0.5 cm by MRI) and allowing up to five intracranial target lesions. CR is defined as disappearance of all lesions. PR is defined as \>=30% decrease in tumor burden, in the absence of CR. The primary endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall ORR | Baseline up to cut of date (approximately 2.5 years) | Overall ORR, defined as the percentage of participants with either a CR or PR in their overall disease (i.e. including intracranial and extracranial disease) based on two consecutive assessments \>= 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. |
| Progression-Free Survival (PFS) | Baseline up to cut of date (approximately 2.5 years) | Intracranial, extracranial and overall PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1. |
| Duration of Response (DOR) | Baseline up to cut of date (approximately 2.5 years) | Intracranial, extracranial and overall DOR, defined as the time from the first occurrence of a documented objective response based on two consecutive assessments ≥ 4 weeks apart to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure. |
| Disease Control Rate (DCR) | At 16 weeks | Intracranial, extracranial and overall DCR, defined as the percentage of participants with a CR or PR or stable disease (SD) at 16 weeks from study treatment initiation, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression is defined as \>=20% increase in tumor burden. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure. |
| Extracranial ORR | Baseline up to cut of date (approximately 2.5 years) | Extracranial ORR, defined as the percentage of participants with either a CR or PR in their extracranial disease based on two consecutive assessments \>=4 weeks apart, as determined by the investigator according to RECIST v1.1. |
| Time to Cognitive Symptom Deterioration | Up to 48 months | Time from study treatment initiation to cognitive symptom deterioration, defined as a change (\>= 10 points on a 0-100 scale) on selected scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-BN20) (visual disorder, motor dysfunction, communication deficit, headaches, seizures and drowsiness). |
| Time to Symptom and Function Deterioration | Up to 48 months | Time from study treatment initiation to symptom and function deterioration defined as a change (\>= 10 points on a 0-100 scale) in fatigue, physical functioning, cognitive functioning, or role functioning as measured by the Fatigue, Physical, Cognitive, Role Functioning scales of the EORTC QLQ-C30. |
| Duration of Stable/Improved Health-related Quality of Life (HRQoL) Scores | Baseline up to cut of date (approximately 2.5 years) | Duration of Stable/Improved HRQoL scores as assessed through use of the two-item Global Health Status (GHS)/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30. |
| Percentage of Participants With Adverse Events | Baseline up to 4 years, 4 months | The safety profile of Cobimetinib plus Atezolizumab and Cobimetinib plus Atezolizumab plus Vemurafenib is evaluated in terms of occurrence and severity of AEs. Severity will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) |
| Overall Survival (OS) | Baseline up to 4 years, 4 months | OS is defined as the time from study treatment initiation to death from any cause. |
Countries
Brazil, France, Germany, Hungary, Italy, Latvia, Spain, Switzerland
Participant flow
Recruitment details
The study was conducted at 21 centers in 7 countries.
Pre-assignment details
A total of 80 participants were enrolled at 21 centers.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1- Cobimetinib and Atezolizumab Participants with BRAFV600 wild-type disease will be administered cobimetinib on Days 1-21 of each 28-day cycle; and atezolizumab on Days 1 and 15 of each treatment cycle. | 15 |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib Participants with BRAFV600 mutation-positive disease will be administered cobimetinib, atezolizumab and vemurafenib in 28-day treatment cycles. Treatment includes a 28-day run-in period where participants will receive cobimetinib and vemurafenib only. Upon completion of the 28-day run-in period, atezolizumab will be added to their treatment regimen | 65 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 11 | 47 |
| Overall Study | Progressive Disease | 0 | 2 |
| Overall Study | Study Terminated By Sponsor | 1 | 13 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
| Overall Study | Withdrawal Of Consent | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Total | Cohort 1- Cobimetinib and Atezolizumab |
|---|---|---|---|
| Age, Continuous | 54.4 Years STANDARD_DEVIATION 13.9 | 55.6 Years STANDARD_DEVIATION 13.8 | 60.9 Years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 9 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 61 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) White | 61 Participants | 72 Participants | 11 Participants |
| Sex: Female, Male Female | 24 Participants | 33 Participants | 9 Participants |
| Sex: Female, Male Male | 41 Participants | 47 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 15 | 47 / 60 | 3 / 5 |
| other Total, other adverse events | 15 / 15 | 60 / 60 | 4 / 5 |
| serious Total, serious adverse events | 6 / 15 | 21 / 60 | 5 / 5 |
Outcome results
Primary
Intracranial Objective Response Rate (ORR)
Intracranial ORR is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) in their intracranial disease based on two consecutive assessments \>= 4 weeks apart. Disease status for this endpoint will be determined by an Independent Review Committee (IRC) in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) with modified measurability definition for intracranial lesions (\>= 0.5 cm by MRI) and allowing up to five intracranial target lesions. CR is defined as disappearance of all lesions. PR is defined as \>=30% decrease in tumor burden, in the absence of CR. The primary endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Population: The evaluable population included all enrolled participants who received study medication and had at least two post-baseline intracranial tumour assessments for response evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Intracranial Objective Response Rate (ORR) | 46.4 Percentage of participants |
Secondary
Disease Control Rate (DCR)
Intracranial, extracranial and overall DCR, defined as the percentage of participants with a CR or PR or stable disease (SD) at 16 weeks from study treatment initiation, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression is defined as \>=20% increase in tumor burden. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.
Time frame: At 16 weeks
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Disease Control Rate (DCR) | Intracranial | 50.8 Percentage of participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Disease Control Rate (DCR) | Extracranial | 50.8 Percentage of participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Disease Control Rate (DCR) | Overall | 50.8 Percentage of participants |
Secondary
Duration of Response (DOR)
Intracranial, extracranial and overall DOR, defined as the time from the first occurrence of a documented objective response based on two consecutive assessments ≥ 4 weeks apart to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Duration of Response (DOR) | Intracranial | 6.7 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Duration of Response (DOR) | Extracranial | 11.6 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Duration of Response (DOR) | Overall | 7.4 Months |
Secondary
Duration of Stable/Improved Health-related Quality of Life (HRQoL) Scores
Duration of Stable/Improved HRQoL scores as assessed through use of the two-item Global Health Status (GHS)/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Population: The PRO-evaluable population included all participants who received any amount of any study medication (e.g., atezolizumab, cobimetinib, or vemurafenib) and had a baseline and at least one post baseline PRO assessment in the questionnaire of interest (EORTC QLQ-C30 or EORTC QLQBN20).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Duration of Stable/Improved Health-related Quality of Life (HRQoL) Scores | NA Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Duration of Stable/Improved Health-related Quality of Life (HRQoL) Scores | 6.14 Months |
Secondary
Extracranial ORR
Extracranial ORR, defined as the percentage of participants with either a CR or PR in their extracranial disease based on two consecutive assessments \>=4 weeks apart, as determined by the investigator according to RECIST v1.1.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Extracranial ORR | 20.0 Percentage of participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Extracranial ORR | 56.9 Percentage of participants |
Secondary
Overall ORR
Overall ORR, defined as the percentage of participants with either a CR or PR in their overall disease (i.e. including intracranial and extracranial disease) based on two consecutive assessments \>= 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Overall ORR | 26.7 Percentage of participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Overall ORR | 52.3 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the time from study treatment initiation to death from any cause.
Time frame: Baseline up to 4 years, 4 months
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Overall Survival (OS) | 13.40 Months |
Secondary
Percentage of Participants With Adverse Events
The safety profile of Cobimetinib plus Atezolizumab and Cobimetinib plus Atezolizumab plus Vemurafenib is evaluated in terms of occurrence and severity of AEs. Severity will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
Time frame: Baseline up to 4 years, 4 months
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Occurrence | 15 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 1 | 1 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 2 | 3 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 3 | 9 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 4 | 1 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 5 | 1 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 5 | 1 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Occurrence | 60 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 3 | 35 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 4 | 10 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 1 | 1 Participants |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Percentage of Participants With Adverse Events | Grade 2 | 13 Participants |
| Cohort 2 - Cobimetinib and Vemurafenib | Percentage of Participants With Adverse Events | Grade 1 | 0 Participants |
| Cohort 2 - Cobimetinib and Vemurafenib | Percentage of Participants With Adverse Events | Grade 2 | 1 Participants |
| Cohort 2 - Cobimetinib and Vemurafenib | Percentage of Participants With Adverse Events | Grade 5 | 2 Participants |
| Cohort 2 - Cobimetinib and Vemurafenib | Percentage of Participants With Adverse Events | Grade 3 | 2 Participants |
| Cohort 2 - Cobimetinib and Vemurafenib | Percentage of Participants With Adverse Events | Occurrence | 5 Participants |
| Cohort 2 - Cobimetinib and Vemurafenib | Percentage of Participants With Adverse Events | Grade 4 | 0 Participants |
Secondary
Progression-Free Survival (PFS)
Intracranial, extracranial and overall PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Progression-Free Survival (PFS) | Intracranial | 2.17 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Progression-Free Survival (PFS) | Extracranial | 4.21 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Progression-Free Survival (PFS) | Overall | 1.81 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Progression-Free Survival (PFS) | Extracranial | 10.68 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Progression-Free Survival (PFS) | Intracranial | 5.78 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Progression-Free Survival (PFS) | Overall | 5.49 Months |
Secondary
Time to Cognitive Symptom Deterioration
Time from study treatment initiation to cognitive symptom deterioration, defined as a change (\>= 10 points on a 0-100 scale) on selected scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-BN20) (visual disorder, motor dysfunction, communication deficit, headaches, seizures and drowsiness).
Time frame: Up to 48 months
Population: The PRO-evaluable population included all participants who received any amount of any study medication (e.g., atezolizumab, cobimetinib, or vemurafenib) and had a baseline and at least one post baseline PRO assessment in the questionnaire of interest (EORTC QLQ-C30 or EORTC QLQBN20).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Visual Disorder | 3.75 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Motor Dysfunction | 1.87 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Communication Deficit | 6.44 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Headaches | NA Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Seizures | 8.31 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Drowsiness | 2.83 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Seizures | NA Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Visual Disorder | 2.99 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Headaches | 10.84 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Motor Dysfunction | 6.70 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Drowsiness | 7.16 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Cognitive Symptom Deterioration | Communication Deficit | 13.90 Months |
Secondary
Time to Symptom and Function Deterioration
Time from study treatment initiation to symptom and function deterioration defined as a change (\>= 10 points on a 0-100 scale) in fatigue, physical functioning, cognitive functioning, or role functioning as measured by the Fatigue, Physical, Cognitive, Role Functioning scales of the EORTC QLQ-C30.
Time frame: Up to 48 months
Population: The PRO-evaluable population included all participants who received any amount of any study medication (e.g., atezolizumab, cobimetinib, or vemurafenib) and had a baseline and at least one post baseline PRO assessment in the questionnaire of interest (EORTC QLQ-C30 or EORTC QLQBN20).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Physical Functioning | NA Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Role Functioning | 2.83 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Fatigue | 1.35 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Cognitive Functioning | 11.99 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Fatigue | 1.45 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Physical Functioning | 11.56 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Cognitive Functioning | 8.25 Months |
| Cohort 2 - Cobimetinib, Atezolizumab and Vemurafenib | Time to Symptom and Function Deterioration | Role Functioning | 4.07 Months |