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Combination of ZEN003694 and Enzalutamide for Advanced Prostate Cancer

A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

Phase 2 Interventional Zenith Epigenetics · NCT04986423

This study is testing if combining a new drug called ZEN003694 with enzalutamide can help men with advanced prostate cancer who didn't do well on previous treatments feel better compared to just using enzalutamide alone.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years and up
SexMale
SponsorZenith Epigenetics Industry-sponsored
Drugs / interventionschemotherapy, Radiation
Locations31 sites (Los Angeles, California and 30 other locations)
Trial IDNCT04986423 on ClinicalTrials.gov

What this trial studies

This Phase 2b clinical trial evaluates the effectiveness of ZEN003694 in combination with enzalutamide compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously progressed on abiraterone. Participants are divided into two cohorts based on their response to prior abiraterone treatment, with specific criteria defining poor responders and those with a better response. The study aims to determine if the combination therapy can improve outcomes for patients who have not responded well to previous treatments.

Who should consider this trial

Good fit: Ideal candidates are males aged 18 years and older with metastatic castration-resistant prostate cancer who have progressed on prior abiraterone treatment.

Not a fit: Patients who have not received prior abiraterone treatment or those who are candidates for chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced prostate cancer who have limited responses to existing therapies.

How similar studies have performed: Other studies have shown promise with combination therapies in advanced prostate cancer, suggesting potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Males age ≥ 18 years
2. Metastatic, castration-resistant, histologically confirmed prostate cancer
3. Surgical castration or continuous medical castration for ≥ 8 weeks prior to screening; serum testosterone \< 50 ng/dL confirmed within 4 weeks of first administration of study drug
4. Have progressed on prior abiraterone treatment by PCWG3 criteria
5. Patients who are not candidates for chemotherapy in the opinion of the investigator or patients who decline chemotherapy
6. Cohort A only - Patient must meet definition of poor responder to abiraterone by one of the following:

   1. Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: \< 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone
   2. Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve a PSA50 response
7. Cohort B only - Patient must meet definition of responder to abiraterone by one of the following:

   1. Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL
   2. Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and PSA50 response
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

1. Any history of brain metastases, prior seizure, conditions predisposing to seizure activity
2. Have previously received an investigational BET inhibitor (including previous participation in this study or a study of ZEN003694)
3. Receipt of prior second-generation androgen receptor inhibitors (e.g. enzalutamide, apalutamide, darolutamide, proxalutamide). Receipt of first-generation AR antagonists (e.g. bicalutamide, nilutamide, flutamide) does not count towards this limit.
4. Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to first dose of study drug)
5. Have received prior systemic anti-cancer therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
6. Have received exogenous administration of testosterone therapy since discontinuation of abiraterone.
7. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
8. Radiation therapy within 2 weeks of the first administration of study drug

Where this trial is running

Los Angeles, California and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Castration-Resistant Prostate CancermCRPCZEN003694ZEN-3694BromodomainBETiEnzalutamideXtandi®
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.