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