NCT04471974

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

Active, enrolled Phase 2 Last updated 22 July 2025

What this trial tests

Phase 2 trial testing BET Bromodomain Inhibitor ZEN-3694 in Castration-Resistant Prostate Carcinoma in 61 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

26 January 2021

Primary endpoint
31 May 2028

31 May 2028

Quick facts

Lead sponsor	Rahul Aggarwal
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	61
Start date	26 January 2021
Primary completion	31 May 2028
Estimated completion	31 May 2028
Sites	3 locations across United States

Drugs / interventions tested

• BET Bromodomain Inhibitor ZEN-3694 — full drug profile →
• Enzalutamide (enzalutamide) — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Castration-Resistant Prostate Carcinoma — all drugs for Castration-Resistant Prostate Carcinoma →
• Metastatic Prostate Adenocarcinoma — all drugs for Metastatic Prostate Adenocarcinoma →
• Metastatic Prostate Small Cell Carcinoma — all drugs for Metastatic Prostate Small Cell Carcinoma →
• Stage IV Prostate Cancer AJCC v8 — all drugs for Stage IV Prostate Cancer AJCC v8 →

Sponsor

Rahul Aggarwal — full company profile →

Who can join

18 and older, male only, with Castration-Resistant Prostate Carcinoma or Metastatic Prostate Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials.
   He Y, Xu W, Xiao YT, Huang H, et al · · 2022 · cited 192× · PMID 35750683 · DOI 10.1038/s41392-022-01042-7
2. MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.
   Ahmadi SE, Rahimi S, Zarandi B, Chegeni R, et al · · 2021 · cited 158× · PMID 34372899 · DOI 10.1186/s13045-021-01111-4
3. Epigenetics-targeted drugs: current paradigms and future challenges.
   Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
4. Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.
   Wang ZQ, Zhang ZC, Wu YY, Pi YN, et al · · 2023 · cited 128× · PMID 37926722 · DOI 10.1038/s41392-023-01647-6
5. BET Proteins as Attractive Targets for Cancer Therapeutics.
   Sarnik J, Popławski T, Tokarz P. · · 2021 · cited 51× · PMID 34681760 · DOI 10.3390/ijms222011102
6. Recent Advances in Epigenetic Biomarkers and Epigenetic Targeting in Prostate Cancer.
   Kumaraswamy A, Welker Leng KR, Westbrook TC, Yates JA, et al · · 2021 · cited 51× · PMID 33785255 · DOI 10.1016/j.eururo.2021.03.005
7. Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy.
   Czajka-Francuz P, Prendes MJ, Mankan A, Quintana Á, et al · · 2023 · cited 46× · PMID 37427115 · DOI 10.3389/fonc.2023.1200646
8. Clinical considerations for the management of androgen indifferent prostate cancer.
   Berchuck JE, Viscuse PV, Beltran H, Aparicio A. · · 2021 · cited 46× · PMID 33568748 · DOI 10.1038/s41391-021-00332-5