ZEN-3694, Enzalutamide, and Pembrolizumab for the Treatment of Metastatic Castration-Resistant Prostate Cancer

This phase II trial investigates how well ZEN-3694, enzalutamide, and pembrolizumab work in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). ZEN-3694 blocks the expression of the MYC gene to prevent cellular growth in certain types of tumors, including castrate resistant prostate cancer. Enzalutamide has been shown to block testosterone from reaching prostate cancer cells by binding to a receptor on prostate cancer cells, called androgen receptors. This works similar to a lock and key. When enzalutamide (key) inserts into the androgen receptor (lock) testosterone cannot attach to the androgen receptor, which slows the growth of tumor cells and may cause them to shrink. Pembrolizumab is a monoclonal antibody (proteins that can protect the body from foreign organisms, such as bacteria and viruses) designed to block a specific control switch which may be activated by tumor cells to overcome the body's natural immune system defenses. It also enhances the activity of the body's immune cells against tumor cells. The purpose of this study is to find out the effects ZEN-3694, enzalutamide, and pembrolizumab on patients with metastatic castration-resistant prostate cancer who have previously experienced disease progression.

NCT Number	NCT04471974
Lead Sponsor	Rahul Aggarwal Collaborators: Zenith Epigenetics, Merck Sharp & Dohme LLC, U.S. Army Medical Research and Development Command
Conditions	Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Metastatic Prostate Small Cell Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8
Enrollment	61 participants
Start Date	2021-01-26
Primary Completion	2028-05-31 (estimated)
Study Completion	2028-05-31 (estimated)
Updated on ClinicalTrials.gov	2026-07-23