PRIMARY OBJECTIVES:~I. To assess the best overall response rate (BORR = complete response + partial response) of the combination of pembrolizumab and imatinib for treatment of melanomas harboring c-Kit mutation or amplification.~II. To evaluate the safety and adverse effect profile of the combination of pembrolizumab and imatinib in patients with melanomas harboring c-KIT aberrations (mutations or amplifications).~SECONDARY OBJECTIVES:~I. To assess the median time to progression (TTP), progression free survival (PFS), and overall survival (OS).~TERTIARY OBJECTIVES:~I. Assessment of programmed cell death ligand (PD-L)1 expression in melanoma patients with c-KIT aberrations before and after combined therapy.~OUTLINE:~Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and imatinib mesylate orally (PO) once daily (QD) on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days and every 9 weeks for 1 year, and then every 12 weeks thereafter.
This phase I/II trial studies the side effects and how well pembrolizumab and imatinib mesylate work in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and imatinib mesylate may work better in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body.