Pembrolizumab and Tazemetostat to Overcome Immune Tolerance Following ASCT or CAR T-cell Therapy in Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma

This phase II trial tests how well pembrolizumab and tazemetostat work to treat patients who have received autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T cell therapy for aggressive non hodgkins lymphoma. A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and tazemetostat may work better to treat patients who have received ASCT or CAR-T cell therapy for aggressive non hodgkins lymphoma.

PRIMARY OBJECTIVE: I. To assess the event-free survival (EFS) for the combination of pembrolizumab and tazemetostat as maintenance for 12 months in patients with aggressive B-cell Non- Hodgkin's Lymphoma following ASCT or CAR T-cell therapy. SECONDARY OBJECTIVES: I. To assess the progression-free survival (PFS) for the combination of pembrolizumab and tazemetostat as maintenance for 12 months in patients with aggressive B-cell Non-Hodgkin's Lymphoma following ASCT or CAR T-cell therapy. II. To assess the overall survival (OS) for the combination of pembrolizumab and tazemetostat as maintenance for 12 months in patients with aggressive B-cell Non-Hodgkin's Lymphoma following ASCT or CAR T-cell therapy. III. To evaluate the safety and toxicity of the combination of pembrolizumab and tazemetostat as maintenance therapy for 12 months following ASCT or CAR T cell therapy. IV. To determine the objective response rate (ORR), complete response (CR) rate and partial response (PR) rate in patients receiving CAR T-cell therapy during maintenance phase (as assessed by Lugano Criteria). EXPLORATORY OBJECTIVES: I. To assess the change in immune cell subsets and cytokines, measured by flow and proteomics, with pembrolizumab alone and in combination with tazemetostat. II. To determine survival outcomes (event free survival \[EFS\], PFS and OS) by type of treatment and line of therapy (ASCT, CAR T-cell therapy in second and third line). OUTLINE: Starting on day 14 after standard of care ASCT or CAR-T cell treatment patients receive pembrolizumab intravenously (IV) on day 1 of each cycle. Starting cycle 2, patients receive tazemetostat orally (PO) twice daily(BID) on days 1-21 of each cycle. Cycles repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening, computed tomography (CT) scan, positron emission tomography (PET) scan, and blood sample collection throughout the study. After completion of study treatment, patients are followed up within 90 days and periodically for up to 18 months.