Testing the Addition of Tazemetostat to the Immunotherapy Drug, Pembrolizumab (MK-3475), in Advanced Urothelial Carcinoma

Metastatic Urothelial Carcinoma Clinical Trial

Official title: A Pilot Study of Tazemetostat and Pembrolizumab (MK-3475) in Advanced Urothelial Carcinoma

Status Active, not recruiting

Clinical Trial Summary

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 (locally advanced ) or from where it first started (primary site) to other places in the body (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.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To conduct a safety lead-in phase that identifies the safe recommended phase II dose for combination tazemetostat and pembrolizumab (MK-3475).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of pembrolizumab (MK-3475) in combination with tazemetostat.

II. To evaluate the objective disease response rate of combination tazemetostat and pembrolizumab (MK-3475) in patients with advanced urothelial carcinoma that is cisplatin resistant (Arm A) or cisplatin ineligible (Arm B).

III. To evaluate the progression free survival to combination tazemetostat and pembrolizumab (MK-3475) in patients with advanced urothelial carcinoma that is cisplatin resistant (Arm A) or cisplatin ineligible (Arm B).

IV. To evaluate immune-related response using tumor response by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) in combination tazemetostat and pembrolizumab (MK-3475) in patients with advanced urothelial carcinoma that is cisplatin resistant (Arm A) or cisplatin ineligible (Arm B) based on irRECIST criteria.

CORRELATIVE OBJECTIVES:

I. To determine if EZH2 and H3K27me3 chromatin methylation determines disease response to EZH2 and PD1 inhibition in metastatic urothelial carcinoma by analyzing baseline tissue samples.

II. To determine if mutations in genes associated with histone methylation determine disease response to EZH2 and PD1 inhibition in metastatic urothelial carcinoma by analyzing baseline tissue samples.

III. To identify the immune response (T cell phenotypes), T-cell clonality with comparison to T-cell infiltrating lymphocytes and neoantigen profile of responsive and resistant urothelial carcinoma treated with combination anti-PD1 and EZH2i by analyzing blood and tissue samples throughout the study.

OUTLINE:

Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial and undergo collection of blood samples on study.

After completion of study treatment, patients are followed up every 3 months for 1 year. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Locally Advanced Urothelial Carcinoma
• Metastatic Urothelial Carcinoma
• Stage III Bladder Cancer AJCC v8
• Stage IV Bladder Cancer AJCC v8
• Urinary Bladder Neoplasms

• NCT number: NCT03854474
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 18, 2019
• Completion date: June 30, 2024