Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma

Inclusion Criteria: * Signed informed consent * Signed HIV testing consent * Life expectancy ≥ 12 weeks * Able to swallow pills * ECOG performance status 2 or less * Adequate bone marrow function * Adequate renal function * Adequate liver function * Negative urine pregnancy test within 7 days prior to commencement of dosing in premenopausal women * Histological diagnosis of unresectable AJCC stage III or stage IV, BRAFV600E/K mutant melanoma * Measurable disease * Accessible tumor that can be biopsied * Naive to targeted therapy (Prior immune-based therapy in the adjuvant setting or for advanced disease will be allowed if \>2 weeks from study entry) Exclusion Criteria: * Active systemic infection * Active autoimmune disease or history of known or suspected autoimmune disease * Active brain metastases or leptomeningeal metastases * Treatment with any immunomodulatory medication within 4 weeks of initiation of study therapy. * Positive test for hepatitis B virus * Positive test for hepatitis C virus * Positive test for human immunodeficiency virus (HIV) * Pregnant, lactating or breast feeding women * Localized radiation therapy within the last 14 days * History of malabsorption * No consumption of the following within 7 days prior to start of treatment: * St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer) * Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor * History or evidence of cardiovascular risk * History or evidence of retinal pathology