Defactinib and VS-6766 for the Treatment of Patients With Metastatic Uveal Melanoma

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.