Analysis of the Kinetics and Effects of Vemurafenib + Cobimetinib on Intratumoral and Host Immunity in Patients With Advanced BRAFV600 Mutant Melanoma: Implications for Combination With Immunotherapy

This study is for patients with malignant melanoma which has spread beyond the local area and cannot be surgically removed, and who have melanoma tumors that are accessible for repeat biopsies. This research study is a way of gaining new knowledge about treatment options for metastatic melanoma. This research study is evaluating the effects of the drugs vemurafenib and cobimetinib on the immune system.

Vemurafenib has been approved by the FDA for treatment of patients with advanced melanoma that harbors a B-RAF mutation. Vemurafenib works by blocking a protein called B-RAF. Researchers have found that a large number of melanomas have mutations (changes) in the BRAF gene. Genes are specific parts of your DNA that contain information on hereditary characteristics such as hair color and eye color. The BRAF gene codes for a protein called B-RAF, which is involved in sending signals in cells that can lead to cell growth. Research has determined that mutations in the BRAF gene at the V600 position cause a change in the B-RAF protein that can drive the growth and spread of melanoma cells.

Cobimetinib (GDC-0973, XL518) is a potent and highly selective inhibitor of MEK1 and MEK2, central components of the RAS/RAF pathway.

The purpose of this research study is to determine how vemurafenib and cobitmetinib may alter the immune system's reaction to melanoma, in order to learn how best to combine immune therapies with vemurafenib in the future.