In this study, the drugs being used are vemurafenib, cobimetinib, and bevacizumab. Vemurafenib has been approved by the FDA for treatment of patients with advanced melanoma that harbors a BRAF mutation. However, vemurafenib in combination with cobimetinib has not been approved by the FDA for the treatment of cancer. Bevacizumab has been approved by the FDA for use in combination with first line chemotherapies for treatment of patients with colorectal, breast and lung cancer. Bevacizumab has not been approved for use in patients with metastatic melanoma.

Vemurafenib and cobimetinib attack different proteins that cause cancer cells to grow. 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. 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. Vemurafenib works by preventing these altered B-RAF proteins from working, and thereby may block the growth and spread of cancer cells in patients with melanoma. Cobimetinib works by blocking a protein called MEK. MEK has been known to promote growth in cancer that carries either a mutation in the BRAF or KRAS genes. The vemurafenib/cobimetinib combination has been used in prior clinical studies. Information from those other research studies suggests that these drugs can shrink melanoma tumors in the majority of patients and slow tumor growth as compared to standard chemotherapy. Another drug to block the BRAF and MEK proteins was recently approved by the FDA in the treatment of patients with B-RAFV600 mutant melanoma. The researchers want to see if using vemurafenib and cobimetinib together will work in a similar way to treat malignant melanoma.

Bevacizumab is a humanized monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer) produced by using recombinant DNA technology. Bevacizumab is an antibody directed against vascular endothelial growth factor or VEGF. VEGF is a potent, specific growth factor with a well-defined role in normal and abnormal blood vessel formation. It is present in a wide variety of normal tissues, but is produced in excess by most solid cancers (tumors). In the setting of cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. Its expression by the tumor has been associated with worse outcome in patients with a number of tumors types including melanoma. In laboratory experiments, bevacizumab inhibits the growth of several different types of human cancer cells by blocking the effects of VEGF.

The purpose of this research study is to determine the effectiveness of using the study drugs vemurafenib, cobimetinib, and bevacizumab together relative to vemurafenib and cobimetinib alone. This study will investigate whether using both study drugs lengthens the amount of time before participants' melanoma worsens, increases the number of people whose melanoma responds to treatment and what the side effects are of using the drugs together rather than separately.