Low Dose Ipilimumab With Pembrolizumab in Treating Patients With Melanoma That Has Spread to the Brain

PRIMARY OBJECTIVE: I. To assess clinical benefit rate (CBR), defined as complete response (CR) + partial response (PR) + stable disease (SD) \> 6 months, in the brain in subjects with melanoma brain metastasis (MBM) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria who are treatment naive to anti-PD-1 agents in the metastatic setting (prior adjuvant anti-PD1 allowed). SECONDARY OBJECTIVES: I. To assess clinical benefit rate (CBR) in the brain in subjects with MBM per modified RECIST 1.1 in patients who previously progressed on PD-1 inhibitors. II. To assess overall survival (OS) and progression free survival (PFS). III. To evaluate the brain-specific safety and tolerability of the combination regimen in subjects with or without stereotactic radiotherapy (SRT) received prior to study entry, or on study. IV. To evaluate cytokine levels and changes in the T-cell population in the cerebrospinal fluid (CSF) and blood in patients treated with combination low dose ipilimumab and pembrolizumab. V. To assess changes in relative apparent diffusion coefficient as measured by magnetic resonance imaging (MRI) as an early predictor of response. VI. To assess changes in circulating cfDNA (cell-free deoxyribonucleic acid) as determinants of response and/or markers of early progression. VII. To evaluate molecular and immunological changes in extracranial lesions. OUTLINE: Patients receive ipilimumab intravenously (IV) over 90 minutes and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles for ipilimumab and up to 35 cycles for pembrolizumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 6 weeks for the first year, and then every 12 weeks thereafter.