Investigational Drug
ZEN-3694
TrialFetch AI Analysis
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Overview
ZEN-3694 (ZEN003694) is an investigational oral cancer drug studied mainly in combination with other treatments. Human results have been reported in metastatic castration-resistant prostate cancer and metastatic triple-negative breast cancer, but the studies described below were single-arm: they cannot establish how much benefit ZEN-3694 adds to its partner drugs. (pmc.ncbi.nlm.nih.gov)
Mechanism of action
ZEN-3694 inhibits bromodomain and extra-terminal (BET) proteins, which help regulate gene expression. Researchers are studying whether BET inhibition can counter treatment resistance, including resistance to androgen-signaling drugs in prostate cancer. In laboratory models, it also reduced expression of DNA-repair genes, providing a rationale for combining it with the PARP inhibitor talazoparib. (pmc.ncbi.nlm.nih.gov)
Efficacy
- Prostate cancer: In a phase 1b/2a study of 75 patients whose cancer had resisted abiraterone and/or enzalutamide, ZEN-3694 plus enzalutamide produced a confirmed PSA50 response—a reduction of at least 50% in prostate-specific antigen—in 6 patients (8%). Median radiographic progression-free survival was 9.0 months. These are outcomes for the combination, not proof of ZEN-3694’s independent effect. (pmc.ncbi.nlm.nih.gov)
- Triple-negative breast cancer: A 2022 conference abstract reported an investigator-assessed objective response rate of 22% (11/50) with ZEN-3694 plus talazoparib in patients without germline BRCA1/2 mutations. The phase 2 portion reported clinical benefit in 30% (11/37). These findings have the additional limitation of being reported in a conference abstract rather than a full trial publication. (ascopubs.org)
Safety
In the 75-patient prostate-cancer study, 14 patients (18.7%) had grade 3 or higher treatment-related adverse events. Commonly reported ZEN-3694-related effects included temporary visual symptoms (67%), nausea (45%) and fatigue (40%); grade 3 thrombocytopenia occurred in 3 patients (4%). These figures come from combination treatment and should not be read as a complete safety profile for ZEN-3694 alone. (pmc.ncbi.nlm.nih.gov)
Further reading
Last updated: Sep 2026
Active trials using ZEN-3694
Found 9 active trials using this drug:
TrialFetch AI summary: Adults with asymptomatic metastatic castration-resistant prostate cancer that has progressed after a second-generation androgen receptor–axis inhibitor receive investigational ZEN-3694, a BET protein inhibitor, plus bipolar androgen therapy. After radiographic progression, they switch to ZEN-3694 plus enzalutamide.
ClinicalTrials.gov ID: NCT06922318
TrialFetch AI summary: Adults with refractory or relapsed BRAF V600E–mutant metastatic colorectal cancer who have progressed after systemic therapy and previously tolerated cetuximab plus encorafenib receive those agents with investigational ZEN-3694, a BET bromodomain inhibitor. The study evaluates dosing and safety of the three-drug combination.
ClinicalTrials.gov ID: NCT06102902
TrialFetch AI summary: Adults with recurrent clear cell or endometrioid ovarian cancer or clear cell or grade 1 endometrioid endometrial cancer after 1–3 prior cytotoxic regimens receive oral tuvusertib, an ATR inhibitor, plus oral ZEN-3694, a BET inhibitor. Dose escalation also permits platinum-resistant high-grade serous ovarian cancer; expansion enrolls separate ARID1A-altered and wild-type cohorts.
ClinicalTrials.gov ID: NCT05950464
TrialFetch AI summary: Adults with metastatic or unresectable solid tumors that progressed after fluoropyrimidine-containing standard therapy receive oral ZEN-3694, an investigational BET protein inhibitor, plus oral capecitabine. Dose expansion is limited to colorectal cancer.
ClinicalTrials.gov ID: NCT05803382
TrialFetch AI summary: Patients aged 12 years or older with metastatic or unresectable solid tumors, including breast cancer and NUT carcinoma, may enter dose escalation if standard options are unavailable or ineffective; expansion is limited to measurable, laboratory-confirmed NUT carcinoma. Treatment combines oral ZEN003694, an investigational BET protein inhibitor, with oral abemaciclib, a CDK4/6 inhibitor.
ClinicalTrials.gov ID: NCT05372640
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic triple-negative breast cancer receive oral ZEN-3694, an investigational BET protein inhibitor, with pembrolizumab and nab-paclitaxel. Dose expansion is limited to patients with PD-L1-negative disease and no more than one prior metastatic systemic therapy; prior metastatic checkpoint inhibitor or taxane therapy is excluded.
ClinicalTrials.gov ID: NCT05422794
TrialFetch AI summary: This single-arm study enrolls adults with measurable recurrent ovarian, fallopian tube, or primary peritoneal carcinoma after prior PARP inhibitor therapy, including both platinum-sensitive and platinum-resistant disease. Patients receive daily oral ZEN003694, an investigational BET inhibitor that alters transcriptional regulation, plus talazoparib, a PARP inhibitor.
ClinicalTrials.gov ID: NCT05071937
TrialFetch AI summary: Adults with previously treated advanced or refractory solid tumors or eligible B- or T-cell lymphomas receive oral ZEN003694, a BET inhibitor, plus entinostat, a class I HDAC inhibitor, in dose escalation. The expansion cohort focuses on locally advanced unresectable or metastatic pancreatic cancer refractory to standard therapy.
ClinicalTrials.gov ID: NCT05053971
TrialFetch AI summary: Men with metastatic castration-resistant prostate cancer who have progressed on abiraterone and are unsuitable for or decline chemotherapy are randomized to enzalutamide alone or enzalutamide plus ZEN003694, with cohorts defined by prior abiraterone response. ZEN003694 is an investigational BET protein inhibitor intended to alter gene expression associated with resistance to androgen-signaling therapy.
ClinicalTrials.gov ID: NCT04986423
