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. 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.
Name: Pembrolizumab
Description: Given IVType: BiologicalTreatment (tazemetostat, pembrolizumab)
Name: Tazemetostat
Description: Given POType: DrugTreatment (tazemetostat, pembrolizumab)
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 yearDescription: Will be assessed using NCI CTCAE version 5. All adverse events will be summarized as to type, grade, timing, frequency and attribution using frequencies and percentages
Measure: Incidence of adverse events Time: Up to 30 days after treatment discontinuationDescription: 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: BaselineSingle 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 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier are not eligible - Patients with a known additional malignancy that is progressing or requires active treatment are not eligible. --- V617F ---