ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer

NCT04986423 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ZEN003694-201
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 31

Brief Summary

This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have progressed on prior abiraterone by PCWG3 criteria. Disease must have progressed on only abiraterone by PCWG3 criteria prior to study entry. The patient population will be separated into two cohorts: Cohort A: Patients with poor response to prior abiraterone defined as:

• 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, or;
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve PSA50 response while on abiraterone Cohort B: Patients with response to prior abiraterone, defined as:
• Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL, or;
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and confirmed PSA50 response

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

mCRPC; ZEN003694; ZEN-3694; Bromodomain; BETi; Enzalutamide; Xtandi®

Outcome Measures

Primary Outcomes (1)

• Cohort A: Radiographic progression-free survival (rPFS) by BICR

  Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.

  Randomization up to 30 months

Secondary Outcomes (17)

• Cohorts A + B: Radiographic progression-free survival (rPFS) by BICR

  Randomization up to 30 months

• Cohort A: Radiographic progression-free survival (rPFS) by investigator assessment

  Randomization up to 30 months

• Cohort A + B: Radiographic progression-free survival (rPFS) by investigator assessment

  Randomization up to 30 months

• Cohort A: Progression-free survival (PFS) by investigator assessment

  Randomization up to 30 months

• Cohort A + B: Progression-free survival (PFS) by investigator assessment

  Randomization up to 30 months

Study Arms (4)

Cohort A - ZEN003694 + Enzalutamide

EXPERIMENTAL

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.

Drug: ZEN003694; Drug: Enzalutamide

Cohort A - Enzalutamide

ACTIVE COMPARATOR

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to Cycle 1 Day 1 (Lead-in). After the Lead-in, patients will be administered enzalutamide 160 mg orally once daily for 28-day cycles. Active control patients will have the option to cross-over to treatment with ZEN003694 in combination with enzalutamide upon confirmed radiographic progression by PCWG3 criteria by independent central review.

Drug: Enzalutamide

Cohort B - ZEN003694 + Enzalutamide

EXPERIMENTAL

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.

Drug: ZEN003694; Drug: Enzalutamide

Cohort B - Enzalutamide

ACTIVE COMPARATOR

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to Cycle 1 Day 1 (Lead-in). After the Lead-in, patients will be administered enzalutamide 160 mg orally once daily for 28-day cycles. Active control patients will have the option to cross-over to treatment with ZEN003694 in combination with enzalutamide upon confirmed radiographic progression by PCWG3 criteria by independent central review.

Drug: Enzalutamide

Interventions

ZEN003694 DRUG

72 mg PO QD

Also known as: ZEN-3694

Cohort A - ZEN003694 + Enzalutamide; Cohort B - ZEN003694 + Enzalutamide

Enzalutamide DRUG

160 mg PO QD

Also known as: Xtandi®, MDV3100

Cohort A - Enzalutamide; Cohort A - ZEN003694 + Enzalutamide; Cohort B - Enzalutamide; Cohort B - ZEN003694 + Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males age ≥ 18 years
• Metastatic, castration-resistant, histologically confirmed prostate cancer
• 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
• Have progressed on prior abiraterone treatment by PCWG3 criteria
• Patients who are not candidates for chemotherapy in the opinion of the investigator or patients who decline chemotherapy
• Cohort A only - Patient must meet definition of poor responder to abiraterone by one of the following:
• 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
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve a PSA50 response
• Cohort B only - Patient must meet definition of responder to abiraterone by one of the following:
• Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and PSA50 response
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Any history of brain metastases, prior seizure, conditions predisposing to seizure activity
• Have previously received an investigational BET inhibitor (including previous participation in this study or a study of ZEN003694)
• 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.
• 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)
• 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
• Have received exogenous administration of testosterone therapy since discontinuation of abiraterone.
• Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
• Radiation therapy within 2 weeks of the first administration of study drug

Sponsors & Collaborators

• Zenith Epigenetics: lead
• Astellas Pharma Inc: collaborator
• Newsoara Biopharma Co., Ltd.: collaborator

Study Sites (31)

California Research Institute

Los Angeles, California, 90027, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94158, United States

RECRUITING

Innovative Clinical Research Institute

Whittier, California, 90603, United States

RECRUITING

Colorado Urology

Lakewood, Colorado, 80228, United States

RECRUITING

D&H Cancer Research Center, LLC

Margate, Florida, 33063, United States

RECRUITING

BRCR Global

Plantation, Florida, 33322, United States

RECRUITING

Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

WITHDRAWN

Maryland Oncology Hematology, P.A.

Columbia, Maryland, 21044, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Weill Cornell Medical College - New York Presbyterian Hospital

New York, New York, 10065, United States

COMPLETED

Messino Cancer Center

Asheville, North Carolina, 28806, United States

RECRUITING

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97223, United States

RECRUITING

Urology Associates, P.C.

Nashville, Tennessee, 37209, United States

RECRUITING

Texas Oncology - Central South

Austin, Texas, 78731, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

RECRUITING

Anhui Provincial Hospital

Hefei, Anhui, 230002, China

RECRUITING

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410006, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

RECRUITING

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

WITHDRAWN

The First Affiliated Hospital of Xi'an Jiaotang University

Xi'an, Shaanxi, 71000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, 200072, China

RECRUITING

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

RECRUITING

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

RECRUITING

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, 310014, China

RECRUITING

MeSH Terms

Interventions

enzalutamide

Central Study Contacts

Zenith Study Team

CONTACT

587-390-7865; ZEN003694-201@zenithepigenetics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: August 2, 2021
• Study Start: September 8, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (16); CN (15)