Oral EPI-7386 in Patients with Castration-Resistant Prostate Cancer

NCT04421222 | Terminated Phase 1 FDA Drug

• 1 other identifier: EPI-7386-CS-001
• Study Type: interventional
• Target: 71
• Locations: 2 countries
• Sites: 9

Brief Summary

This is a phase I, clinical research study of EPI-7386, an investigational drug being studied as a treatment for patients with prostate cancer. All patients in the study will receive EPI-7386. Since this is the first study of EPI-7386 in humans, there is no information about how it affects people or what dose should be used. Therefore, the main purpose of this study is to assess the safety (side effects) of EPI-7386 and to find a dose that can be given without unacceptable side effects. There are other important things that will be evaluated during the study:

• How the amount of EPI-7386 in the blood changes over time.
• The effect of EPI-7386 on prostate cancer.
• The effect of EPI-7386 on certain substances in the body.
• The possibility that EPI-7386 can interact with other drugs. The study will be conducted in 2 parts:
• Part A: To evaluate the safety and tolerability of EPI-7386 as a single agent via 2 Phases:
• Phase 1a: Dose Escalation (mCRPC)
• Phase 1b: Dose Expansion (mCRPC)
• Part B: To evaluate 2 parallel enrolling cohorts (Cohort 1 and Cohort 2) of EPI-7386 in combination of apalutamide acetate + prednisone (AAP) or apalutamide (APA):
• Cohort 1: Combination with AAP in mHSPC or mCRPC patients
• Cohort 2: Will evaluate the anti-tumor activity of EPI-7386 for a limited window of time (12 weeks EPI-7386 monotherapy prior to the start of combination therapy with APA) in nmCRPC patients unperturbed by previous 2nd generation anti-androgen therapies or chemotheraphy.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• The primary safety variable for Part A/Phase 1a of the study is the incidence of protocol-defined DLT during the DLT assessment period (first 28 days of dosing).

  The DLTs will be characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for AEs \[NCI CTCAE version 5.0\]), timing, seriousness, and relationship to study drug.

  2 months

• The primary efficacy variable for Part A/Phase 1b is the proportion of patients with a decline from baseline in PSA blood concentrations of ≥50% and ≥90% at any time point during daily dosing with EPI-7386.

  12 months

• The primary efficacy variable for Part B/Cohort 1 is the incidence of protocol-defined DLT during the DLT assessment period (first 28 days of dosing); TEAEs; abnormalities in clinical laboratory parameters/vitals/ECGs; and changes in ECOG.

  The DLTs will be characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for AEs \[NCI CTCAE version 5.0\]), timing, seriousness, and relationship to study drug. TEAEs and abnormalities in clinical laboratory parameters/vitals/ECGs will be characterized by type, frequency, severity, timing, seriousness and relationship to study treatment.

  6 months

• The primary efficacy variable for Part B/Cohort 2 is the proportion of patients with a decline from baseline in PSA blood concentrations of ≥50% and ≥90% at any time point during daily dosing with single agent EPI-7386 up to Week 12.

  4 months

Study Arms (15)

Part A/Phase 1a: Cohort 1 (Completed)

EXPERIMENTAL

200 mg EPI-7386

Drug: EPI-7386 (QD)

Part A/Phase 1a: Cohort 2 (Completed)

EXPERIMENTAL

400 mg EPI-7386

Drug: EPI-7386 (QD)

Part A/Phase 1a: Cohort 3 (Completed)

EXPERIMENTAL

600 mg EPI-7386

Drug: EPI-7386 (QD)

Part A/Phase 1a: Cohort 4 (Completed)

EXPERIMENTAL

800 mg EPI-7386

Drug: EPI-7386 (QD)

Part A/Phase 1a: Cohort 5 (Completed)

EXPERIMENTAL

1000 mg EPI-7386

Drug: EPI-7386 (QD)

Part A/Phase 1a: Cohort 6 (Completed)

EXPERIMENTAL

800 mg EPI-7386

Drug: EPI-7386 (BID)

Part A/Phase 1a: Cohort 7 (Completed)

EXPERIMENTAL

1200 mg EPI-7386

Drug: EPI-7386 (BID)

Part A/Phase 1b: Cohort 1 (Completed)

EXPERIMENTAL

600 mg EPI-7386 BID

Drug: EPI-7386 (BID)

Part A/Phase 1b: Cohort 2

EXPERIMENTAL

600 mg EPI-7386 QD

Drug: EPI-7386 (QD)

Part B/Cohort 1a

EXPERIMENTAL

600 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Drug: EPI-7386 (QD); Drug: Abiraterone acetate

Part B/Cohort 1b

EXPERIMENTAL

800 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Drug: EPI-7386 (QD); Drug: Abiraterone acetate

Part B/Cohort 1c

EXPERIMENTAL

1200 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Drug: EPI-7386 (BID); Drug: Abiraterone acetate

Part B/Cohort 2a

EXPERIMENTAL

600 mg EPI-7386 monotherapy for 12 weeks then 600 mg EPI-7386 + 240 mg Apalutamide

Drug: EPI-7386 (QD); Drug: Apalutamide

Part B/Cohort 2b

EXPERIMENTAL

800 mg EPI-7386 monotherapy for 12 weeks then 800 mg EPI-7386 + 240 mg Apalutamide

Drug: EPI-7386 (QD); Drug: Apalutamide

Part B/Cohort 2c

EXPERIMENTAL

1200 mg EPI-7386 monotherapy for 12 weeks then 1200 mg EPI-7386 + 240 mg Apalutamide

Drug: EPI-7386 (BID); Drug: Apalutamide

Interventions

EPI-7386 (QD) DRUG

Once daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 1 (Completed); Part A/Phase 1a: Cohort 2 (Completed); Part A/Phase 1a: Cohort 3 (Completed); Part A/Phase 1a: Cohort 4 (Completed); Part A/Phase 1a: Cohort 5 (Completed); Part A/Phase 1b: Cohort 2; Part B/Cohort 1a; Part B/Cohort 1b; Part B/Cohort 2a; Part B/Cohort 2b

EPI-7386 (BID) DRUG

Twice daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 6 (Completed); Part A/Phase 1a: Cohort 7 (Completed); Part A/Phase 1b: Cohort 1 (Completed); Part B/Cohort 1c; Part B/Cohort 2c

Abiraterone acetate DRUG

Once daily dose of abiraterone acetate

Part B/Cohort 1a; Part B/Cohort 1b; Part B/Cohort 1c

Apalutamide DRUG

Once daily dose of apalutamide

Part B/Cohort 2a; Part B/Cohort 2b; Part B/Cohort 2c

Eligibility Criteria

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

You may qualify if:

• Male 18 years of age or older.
• Histologically, pathologically, or cytologically confirmed prostate cancer without small cell features.
• 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.
• Limited further treatment options available known to confer clinical benefit in this disease setting from the perspective of the treating physician. Specifically, patients must have progressed on at least 2, but not more than 3, prior approved systemic therapies for mCRPC which include at least one, but not more than 2, second generation anti-androgen drug.
• Patients may have received prior docetaxel for mCSPC or mCRPC but must not have had disease progression during, or within 6 months of completing chemotherapy. Only one line of prior chemotherapy is allowed.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• The patient must have recovered from toxicities related to any prior treatments.
• Castrate at screening.
• Patients receiving bisphosphonates or other approved bone-targeting therapy must be on a stable dose for at least 4 weeks prior to the start of study drug.
• Demonstrate adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Patients are eligible to enroll in this cohort if they meet the clinical criteria for receiving AAP as standard of care treatment as per label (i.e., high-risk mHSPC or mCRPC).
• Part B/Cohort 2 (Window of Opportunity with clinical endpoints followed by combination with Apalutamide)
• Male 18 years of age or older.

You may not qualify if:

• Biologic anti-cancer therapy or a cytotoxic chemotherapy within 4 weeks prior to the start of study drug.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 4 weeks prior to the start of study drug.
• Any lutamides or abiraterone within 14 days or 5 half-lives, whichever is longer prior to start of study drug.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study drug.
• Received limited-field palliative bone radiotherapy \>5 fractions and/or any radiotherapy within 2 weeks prior to the start of study drug.
• Received a blood transfusion within 28 days of screening.
• Received prior chemotherapy (for Part 1b Cohort A only).
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 4 weeks before enrollment.
• Spinal cord compression.
• Diagnosis of another invasive malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma.
• Gastrointestinal disorder affecting absorption.
• Significant cardiovascular disease.
• Concurrent disease or any clinically significant abnormality.
• Use of strong inducers of CYP3A within 14 days of the first dose of study drug.
• Any prior treatment with chemotherapy.

Sponsors & Collaborators

• ESSA Pharmaceuticals: lead

Study Sites (9)

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Center of NV Las Vegas

Las Vegas, Nevada, 89169, United States

Location

Great Lakes Cancer Center

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

BC Cancer

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X0A9, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

BID protein, human; Abiraterone Acetate; apalutamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 9, 2020
• Study Start: June 23, 2020
• Primary Completion: October 31, 2024
• Study Completion: December 3, 2024
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); CA (2)