A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC)

A Phase 1b Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone or Apalutamide in mCRPC (ARES: Androgen Receptor Eradication Study)

The purpose of this study is to determine safety, including dose limiting toxicities, and the recommended phase 2 dose (RP2D) of EPI-7386 in separate combinations with (a) abiraterone acetate plus prednisone or prednisolone (AAP) and (b) apalutamide (dose-finding) and to determine the antitumor activity of EPI-7386 in separate combinations with (a) AAP and (b) apalutamide (dose-expansion).

Study Overview

• Status: Terminated
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: EPI-7386; Drug: Abiraterone Acetate; Drug: Prednisone or Prednisolone; Drug: Apalutamide

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • Prostate Cancer Centre
• United States
  • Maryland
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology Research Associates
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • GU Research Network
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed prostate adenocarcinoma
• Must be able to continue Gonadotropin-releasing hormone agonist (GnRHa) during the study if not surgically castrate
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2
• Must be able to swallow oral medicines
• Contraceptive use by men (and female partners of men enrolled in the study who are of childbearing potential or are pregnant) (birth control) use should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

• Known central nervous system (CNS) metastases
• Non-metastatic castration-resistant prostate cancer (CRPC) (biochemical or locoregional disease only) is excluded from trial participation
• Evidence of predominant neuroendocrine/small cell carcinoma features in archival or baseline tumor biopsy specimen(s)
• Symptomatic or impending spinal cord compression, except if participant has received definitive treatment and demonstrates evidence of clinically stable disease
• Known disorder affecting gastrointestinal absorption

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP); Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP.	Drug: EPI-7386; EPI-7386 will be administered orally once daily.; Drug: Abiraterone Acetate; Abiraterone Acetate will be administered orally once daily.; Drug: Prednisone or Prednisolone; Prednisone or Prednisolone will be administered orally twice daily.
Experimental: Group B: EPI-3786 + Apalutamide; Participants with mCRPC will receive EPI-7386 + apalutamide to determine RP2D dose of EPI-7386 in combination with apalutamide in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with apalutamide.	Drug: EPI-7386; EPI-7386 will be administered orally once daily.; Drug: Apalutamide; Apalutamide will be administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 3 Years 3 Months
Number of Participants with AEs by Severity	Number of participants with AEs by severity will be reported.	Up to 3 Years 3 Months
Number of Participants with Dose-limiting Toxicities (DLT)	The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.	Up to 28 days of Cycle 1 (each cycle of 28 days)
Composite Response Rate	Composite response rate at 12 weeks, defined as either 90 percent (%) reduction in prostate-specific antigen (PSA) level from baseline (PSA-90), or objective response (confirmed per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in participants with measurable disease, or both at 12 weeks.	At 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone	Cmax is defined as the maximum observed serum concentration of EPI-7386 and abiraterone.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone	Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and abiraterone.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone	AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and abiraterone.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone	Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone	The observed accumulation ratio for Cmax, determined after multiple dose administration of EPI-7386 and abiraterone (Cycle[C] 2 Day[D] 1/C1D1 and C3D1/C1D1).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone	The observed accumulation ratio for AUCtau, determined after multiple dose administration of EPI-7386 and abiraterone (C2D1/C1D1 and C3D1/C1D1).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide	Cmax is defined as the maximum observed serum concentration of EPI-7386 and apalutamide.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide	Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and apalutamide.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide	AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and apalutamide.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide	Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide	The observed accumulation ratio for Cmax, determined after multiple dose administration EPI-7386 and apalutamide (C2D1/C1D1 and C3D1/C1D1).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide	The observed accumulation ratio for AUCtau, determined after multiple dose administration EPI-7386 and Apalutamide (C2D1/C1D1 and C3D1/C1D1).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Serum Prostate-Specific Antigen (PSA)	Serum PSA concentration will be measured.	Up to 3 Years 3 Months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: March 24, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisolone; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: CR109122; 81712917PCR2001 (Other Identifier: Janssen Research & Development, LLC); 2022-000946-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No