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

NCT05075577 | Terminated Phase 1 FDA Drug

• 1 other identifier: EPI-7386-CS-010
• Study Type: interventional
• Target: 77
• Locations: 3 countries
• Sites: 24

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (6)

Phase 1 Cohort 1

EXPERIMENTAL

600 mg QD EPI-7386 in combination of Enzalutamide120 mg

Drug: EPI-7386 with Enzalutamide

Phase 1 Cohort 2

EXPERIMENTAL

800 mg QD EPI-7386 in combination of Enzalutamide120 mg

Drug: EPI-7386 with Enzalutamide

Phase 1 Cohort 3

EXPERIMENTAL

600 mg BID EPI-7386 in combination of Enzalutamide120 mg

Drug: EPI-7386 with Enzalutamide

Phase 1 Cohort 4

EXPERIMENTAL

RP2D mg EPI-7386 in combination of Enzalutamide160 mg

Drug: EPI-7386 with Enzalutamide

Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)

EXPERIMENTAL

RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg

Drug: EPI-7386 with Enzalutamide

Phase 2 Enzalutamide single agent

ACTIVE COMPARATOR

Enzalutamide 160 mg

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Daily oral dose of enzalutamide

Phase 2 Enzalutamide single agent

EPI-7386 with Enzalutamide DRUG

Daily oral dose of EPI-7386 in combination of enzalutamide

Phase 1 Cohort 1; Phase 1 Cohort 2; Phase 1 Cohort 3; Phase 1 Cohort 4; Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ESSA Pharmaceuticals: lead

Study Sites (24)

Arizona Urology

Tucson, Arizona, 85741, United States

Location

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Chesapeake Urology Associates

Baltimore, Maryland, 21204, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Washington University Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Great Lakes Cancer Center

Buffalo, New York, 14203, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

OHSU Knight Cancer Instititue

Portland, Oregon, 97239, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

The Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Prostate Cancer Centre

Calgary, Alberta, T2V 1P9, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre, Hamilton, ON L8V 5C2

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 0A9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: October 13, 2021
• Study Start: December 21, 2021
• Primary Completion: October 31, 2024
• Study Completion: January 14, 2025
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

AU (4); US (13); CA (7)