PRIMARY OBJECTIVE:~I. To investigate the potential efficacy of the combination of defactinib hydrochloride (defactinib [VS-6063]) and Raf/MEK serine/threonine kinase inhibitor RO5126766 (VS-6766) in patients with metastatic uveal melanoma.~SECONDARY OBJECTIVES:~I. To assess the effectiveness of defactinib in combination with VS-6766 in patients with metastatic uveal melanoma (MUM).~II. To assess the safety and toxicity profile of the combination of defactinib and VS6766.~EXPLORATORY OBJECTIVES:~I. To study the pharmacodynamic profile of defactinib in combination with VS-6766 in pre-treatment, on-treatment, and post-treatment tumor biopsies.~II. To investigate mechanisms of resistance to the combination of defactinib and VS-6766.~III. To investigate the potential efficacy of circulating cell free deoxyribonucleic acid (DNA) for prediction/monitoring.~OUTLINE:~Patients receive defactinib orally (PO) twice daily (BID) and VS-6766 PO twice a week (BIW) (Monday and Thursday or Tuesday and Friday) for 3 weeks in every cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy at baseline, after cycle 1 or 2, and post-treatment.~After completion of study treatment, patients are followed every 3 months until death or up to 2 years after the last patient is enrolled.
This phase II trial studies the effect of combining defactinib and VS-6766 in treating patients with uveal melanoma that has spread to other places in the body (metastatic). The way cells communicate with one another (different cell signaling pathways) are overactive in uveal melanoma tumor cells. Giving defactinib together with VS-6766 may block pathways that are important for the growth of uveal melanoma cells, and may result in shrinkage or stabilization of the cancer and prolonged time to disease progression and survival.