EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC

A Phase 1/2 Study of EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with Metastatic Castration-Resistant Prostate Cancer

This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in subjects with mCRPC.

Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the safety and tolerability of the drug combination and establish the RP2CDs for EPI-7386 and enzalutamide when dosed in combination. In addition, blood sampling will be conducted for PK evaluation to assess the potential DDI between the two drugs.

Once the RP2CD for each drug has been established, Phase 2 of the study will commence. Phase 2 is a two-arm, randomized (2:1), open-label study. Approximately 120 subjects will be randomized 2:1 to:

• Group 1: EPI-7386 at the RP2CD + enzalutamide(depending on the results of the Phase 1) (n=80)
• Group 2: Enzalutamide single agent (n=40) The planned dose of enzalutamide and EPI-7386 for the combination arm will be those determined in the Phase 1 of this study based on safety and exposure data. Subjects may remain on study treatment as long as they are tolerating treatment without disease progression based on RECIST v1.1 and/or PCWG3.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: EPI-7386 with Enzalutamide; Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • The Canberra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital Sydney
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Calgary, Alberta, Canada, T2V 1P9
      • Prostate Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre, Hamilton, ON L8V 5C2
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Center
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Université de Montréal
• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Arizona Urology
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates Of The Treasure Coast
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21204
      • Chesapeake Urology Associates
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Comprehensive Cancer Center
    • Buffalo, New York, United States, 14203
      • Great Lakes Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Instititue
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males ≥18 years.
• Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
• Naïve to second generation anti-androgens.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone.
• Serum testosterone ≤1.73 nmol/L (50 ng/dL).
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment.
• Demonstrate adequate organ function.

Exclusion Criteria:

• Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
• Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment.
• Received a blood transfusion within 28 days of hematologic screening labs.
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent.
• Spinal cord compression.
• Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies.
• Gastrointestinal issues affecting absorption.
• Significant cardiovascular disease.
• Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
• Concurrent disease or any clinically significant abnormality.
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
• Use of strong inhibitors of CYP2C8.
• Use of strong inducers of CYP3A.
• Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6.
• Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.
• Not a candidate for enzalutamide treatment.
• Patients with rare hereditary problems of fructose intolerance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Cohort 4; RP2D mg EPI-7386 in combination of Enzalutamide160 mg	Drug: EPI-7386 with Enzalutamide; Daily oral dose of EPI-7386 in combination of enzalutamide
Experimental: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1); RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg	Drug: EPI-7386 with Enzalutamide; Daily oral dose of EPI-7386 in combination of enzalutamide
Active Comparator: Phase 2 Enzalutamide single agent; Enzalutamide 160 mg	Drug: Enzalutamide; Daily oral dose of enzalutamide
Experimental: Phase 1 Cohort 1; 600 mg QD EPI-7386 in combination of Enzalutamide120 mg	Drug: EPI-7386 with Enzalutamide; Daily oral dose of EPI-7386 in combination of enzalutamide
Experimental: Phase 1 Cohort 2; 800 mg QD EPI-7386 in combination of Enzalutamide120 mg	Drug: EPI-7386 with Enzalutamide; Daily oral dose of EPI-7386 in combination of enzalutamide
Experimental: Phase 1 Cohort 3; 600 mg BID EPI-7386 in combination of Enzalutamide120 mg	Drug: EPI-7386 with Enzalutamide; Daily oral dose of EPI-7386 in combination of enzalutamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Incidence of Dose Limiting Toxicities	Characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE version 5.0]), timing in relation to study treatment administration, seriousness, and relationship to study treatment.	Baseline to End of Cycle 1 (each cycle is 28 days)
Phase 1: Incidence of treatment emergent adverse events	Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.	Baseline to 30 days after last dose of study drug
Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386	Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.	Baseline to 30 days after last dose of study drug
Phase 1: Changes in ECOG performance status		Baseline to 30 days after last dose of study drug
Phase 2: Proportion of subjects with a prostate-specific antigen decline of >90% (PSA90) at Week 12		Baseline to Week 12

Collaborators and Investigators

• Sponsor: ESSA Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): January 14, 2025

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: EPI-7386-CS-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No