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