PRIMARY OBJECTIVES:~I. To evaluate antitumor activity of high dosing regimen of encorafenib + binimetinib combination therapy for patients with BRAFV600-mutant melanoma brain metastases and/or leptomeningeal disease (LMD) as measured by progression free survival (PFS).~II. To evaluate the safety/tolerability of high dosing regimen of encorafenib + binimetinib combination therapy for patients with BRAFV600-mutant melanoma brain metastases and/or LMD.~SECONDARY OBJECTIVE:~I. To further evaluate antitumor activity of high dosing regimen of encorafenib + binimetinib combination therapy for patients with BRAFV600-mutant melanoma and/or LMD, as measured by brain metastasis response rate (BMRR), extracranial response rate, global response rate, brain metastases disease control rate (DCR), overall survival (OS), and duration of response (DOR).~EXPLORATORY OBJECTIVES:~I. To compare the immunological effects of this treatment on immune cells in the cerebrospinal fluid (CSF) to those observed in the peripheral blood.~II. To compare levels of encorafenib and binimetinib in the CSF and peripheral blood.~III. To assess neurocognitive function as measured by the Montreal Cognitive Assessment (MoCA) and MD Anderson Symptom Inventory brain tumor module (MDASI-BT).~OUTLINE:~Patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on day 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.
This phase II trial studies the effects of binimetinib and encorafenib in treating patients with melanoma that has spread to the central nervous system (metastases). Binimetinib and encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and encorafenib may help control melanoma that has spread to the brain.