PRIMARY OBJECTIVES:~I. To assess the safety and tolerability of vorinostat plus pembrolizumab therapy by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.~II. To determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of vorinostat when given in combination with pembrolizumab.~SECONDARY OBJECTIVE:~I. To obtain preliminary estimates of the anti-tumor activity of pembrolizumab plus vorinostat therapy by assessing the overall response rate (ORR), complete response (CR) rate, duration of response (DOR), overall survival (OS) and progression-free survival (PFS).~EXPLORATORY OBJECTIVES:~I. Evaluate responses and disease progression according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).~II. Explore genomic biomarkers of response and resistance to pembrolizumab plus vorinostat therapy in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or Hodgkin lymphoma (HL).~III. Explore immunologic biomarkers of response and resistance to pembrolizumab plus vorinostat therapy in patients with DLBCL, FL, or HL.~IV. Explore the value of circulating deoxyribonucleic acid (DNA) (ctDNA) as a biomarker of response to pembrolizumab plus vorinostat therapy.~OUTLINE: This is a dose-escalation study of vorinostat.~Patients receive vorinostat orally (PO) twice daily (BID) on days 1-5 and 8-12 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for 24 months 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.
This phase I trial studies the side effects and best dose of vorinostat when given together with pembrolizumab in treating patients with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma that has come back after a period of improvement or that does not respond to treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat and pembrolizumab together may work better than pembrolizumab alone in treating patients with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma.