The Effects of Vemurafenib + Cobimetinib on Immunity in Patients With Melanoma

This is multicenter study of vemurafenib and cobimetinib in patients with biopsy-accessible advanced metastatic melanoma. The trial will consist of a screening period, a treatment phase, and one post-study follow-up visit occurring about 30 days after the last dose of drug. Day 1 of the study will be defined as the first day a subject receives vemurafenib and/or cobitmetinib. During the treatment phase, all study assessments will be conducted on Day 1 (± 3 days) of each cycle, with the exception of computed tomography (CT) and/or magnetic resonance imaging (MRI), which should occur every 6 weeks (+/- 7 days). All subjects will have biopsies performed of safely accessible tumors before starting treatment and at 1, 2, and 4 weeks later (days 8, 15, 29). In addition, any patient with accessible tumor at the time of progression will have a tumor biopsy performed at that time. Mixed-effects models will be used to study the change in CD8 T cell counts per mm\^2 of tissue, changes in expression of immunoinhibitory proteins (B7-H1/PD-L1, IDO, arginase), and changes in endothelial homing receptor ligands and tumor associated chemokines at pre-treatment at pre-treatment and at weeks 1, 2, and 4 after therapy. Subjects will be treated as random effects to account for individual variability. Potential covariates are age, gender, and ECOG performance status. 60 ml of blood for lymphocytes will be drawn on days 1, 8, 15, and 29.