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

Status: Recruiting
Diagnosis: Melanoma
NCT ID: NCT01656642 (View complete trial on
DFCI Protocol ID: 12-376


This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (anti-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.


Conducting Institutions:
Beth-Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Frank Stephen Hodi, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
David McDermott, MD, Beth Israel Deaconess Medical Center
Donald Lawrence, MD, Massachusetts General Hospital

Dana-Farber Cancer Institute: Janice Russell,
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAF V600 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 (ECOG) performance status of 0 or 1 - Adequate hematologic and end organ function - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 effective forms of contraceptive methods including at least 1 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 2 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 and optional, but encouraged in Escalation Cohorts 2 & 3) 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 (PD)-1 or programmed death-ligand 1 (PD-L1) targeted therapy or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) targeted therapy, including ipilimumab (this exclusion criterion does not apply to patients enrolled in Expansion Cohort A) - Receipt of prior mitogen-activated protein kinase (MAPK) inhibitor pathway agents, including mitogen-activated protein kinase (MEK) 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 CYP3A4 enzyme inducer) or grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor) within 7 days prior to initiation of study 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
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