A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma

Genentech, Inc.67 enrolled

Overview

This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (anti-programmed death-ligand 1 \[PD-L1\] antibody) in combination with vemurafenib or vemurafenib plus cobimetinib in participants with BRAFV600-mutation positive metastatic melanoma. Enrolled participants may continue treatment until they are no longer experiencing clinical benefit as assessed by the investigator and in alignment with the protocol.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Malignant Melanoma

Interventions

AtezolizumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAFV600 Mutation Test. Origin of the primary tumor may be of skin, mucosal, or acral locations but not of uveal origin. Participants having an unknown primary tumor may be eligible if uveal melanoma can be ruled out * Eastern Cooperative Oncology Group performance status of 0 or 1 * Adequate hematologic and end organ function * Measurable disease per RECIST v1.1 * For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use two effective forms of contraceptive methods including at least one that results in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 6 months after the last dose of study drug * For men, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm * Agreement to mandatory archival tissue or fresh biopsy * Agreement to the collection of serial fresh lesion samples (required, if feasible, for entry into Escalation Cohorts 4 and Expansion Cohorts A \& B and optional, but encouraged in Escalation Cohorts 2 \& 3 and Expansion Cohort C) Exclusion Criteria: * Receipt of prior systemic anti-cancer therapy for unresectable, locally advanced or metastatic melanoma * Receipt of prior immunomodulatory agents, including programmed death-1 or PD-L1 targeted therapy or cytotoxic T-lymphocyte-associated antigen 4 targeted therapy including ipilimumab (this exclusion criterion does not apply to participants enrolled in Expansion Cohort A) * Receipt of prior mitogen-activated protein kinase inhibitor pathway agents including mitogen-activated protein kinase inhibitor and BRAF kinase inhibitor * Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the study * Radiotherapy less than or equal to (\<=) 7 days prior to Day 1 * Adverse events from prior anti-cancer therapy that have not resolved to Grade \<= 1 except for alopecia * Any active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years * For participants to be enrolled into the vemurafenib+cobimetinib+ atezolizumab cohorts: history of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration * Pregnant or breastfeeding women * Intake of St. John's wort or hyperforin (potent cytochrome P450 \[CYP\] 3A4 enzyme inducer) or grapefruit juice (potent CYP3A4 enzyme inhibitor) within 7 days preceding the start of study treatment to the end of treatment * Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation or known hypersensitivity to any component of cobimetinib or vemurafenib * Inability to comply with study and follow-up procedures

Locations (8)

UCLA

Los Angeles, California, United States

The Angeles Clinic and Research Institute - W LA Office

Los Angeles, California, United States

University of Colorado Health Science Center; Biomedical Research Bldg. Room 511

Aurora, Colorado, United States

Florida Cancer Specialists - Sarasota

Sarasota, Florida, United States

Massachusetts General Hospital.

Boston, Massachusetts, United States

Dana Farber Can Ins

Boston, Massachusetts, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

Percentage of Participants With Dose Limiting Toxicities

Time frame: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab

Percentage of Participants With Adverse Events

Time frame: Baseline up to approximately 6 years

Secondary Outcomes

Area Under the Concentration-Time Curve (AUC) of Atezolizumab

Time frame: Predose (0 hour), 30 minutes postdose on Day (D) 1 of Cycles (C) 1, 2; predose on D15, D8 of C1; predose on D1 of C3, 4, 5, 7, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days)

Maximum Serum Concentration of Atezolizumab

Maximum Plasma Concentration of Vemurafenib

Time frame: Run-in period: predose (0 hour) on D1, 8, and 22, 3 hours postdose on D22; combination treatment period: predose (0 hour) on D1 of C1 and 2, 3 hours postdose on D1 of C2 (Cycle = 28 days)

Minimum Observed Plasma Trough Concentration (Cmin) of Vemurafenib

Time frame: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 of C1 and 2 (Cycle = 28 days)

Maximum Plasma Concentration of Cobimetinib

Time frame: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 and 15 of C1 and D15 of C2, 3 hours postdose on D15 of Cycle 1 (Cycle = 28 days)

Cmin of Cobimetinib

Time frame: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 and 15 of C1 and D15 of C2 (Cycle = 28 days)

Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)

Time frame: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

Percentage of Participants with Objective Response According to RECIST v1.1

Percentage of Participants with Objective Response According to Immune-Related Response Criteria (irRC)

Duration of Objective Response According to RECIST v1.1

Duration of Objective Response According to irRC

Progression Free Survival According to RECIST v1.1

Progression Free Survival According to irRC

Overall Survival Duration

Time frame: Baseline until death up to 6 years

Mean Atezolizumab Dose

Time frame: Approximately 12 months

Total Number of Atezolizumab Cycles

Time frame: Approximately 12 months

Percentage of Participants With Anti-Atezolizumab Antibodies

Time frame: Predose (0 hour) on D1 (run-in period), predose (0 hour) on D1 of C2, 3, 4, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days)