This phase I/II trial studies the side effects and best dose of tazemetostat and how well it works when given together with pembrolizumab in treating patients with urothelial carcinoma that has spread to nearby tissue or lymph nodes or other places in the body (locally advanced/metastatic). Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tazemetostat and pembrolizumab may work better in treating patients with urothelial carcinoma compared to pembrolizumab without tazemetostat.
Description: Response rates will be summarized in each cohort by proportions and 95% exact confidence intervals. Time to progression will be summarized using the Kaplan-Meier product limit curve.Measure: Objective response rate (ORR) Time: Up to 1 year
Description: Will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. All adverse events will be summarized as to type, grade, timing, frequency and attribution using frequencies and percentagesMeasure: Incidence of adverse events Time: Up to 30 days after treatment discontinuation
Description: Will determine if EZH2, H3K27me3 and mutations in genes associated with histone methylation determine disease response to EZH2 and PD1. Each gene will be related to response using Fisher's exact test.Measure: EZH2 and H3K27me3 chromatin methylation and mutations in genes associated with histone methylation Time: Baseline
Single Group Assignment
There is one SNP
JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing are not eligible - Patients with a prior history of T-cell lymphoblastic lymphoma (T-LBL) or T-cell acute lymphoblastic leukemia (T-ALL) are not eligible - Patients who have received prior PD-L1/PD-1/PD-L2 or EZH2 inhibitor therapy are not eligible - Patients who have had a prior monoclonal antibody within 4 weeks prior to study day 1 are not eligible - Patients with a known additional malignancy that is progressing or requires active treatment are not eligible. --- V617F ---