EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC

• ClinicalTrials.gov Identifier: NCT05075577
• Recruitment Status: Recruiting
• First Posted: October 13, 2021
• Last Update Posted: March 6, 2023
• Sponsor: ESSA Pharmaceuticals
• Information provided by (Responsible Party): ESSA Pharmaceuticals

Tracking Information

• First Submitted Date: September 14, 2021
• First Posted Date: October 13, 2021
• Last Update Posted Date: March 6, 2023
• Actual Study Start Date: December 21, 2021
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 7, 2021)

• Phase 1: Incidence of Dose Limiting Toxicities [ Time Frame: Baseline to End of Cycle 1 (each cycle is 28 days) ]
  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.
• Phase 1: Incidence of treatment emergent adverse events [ Time Frame: Baseline to 30 days after last dose of study drug ]
  Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.
• Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386 [ Time Frame: Baseline to 30 days after last dose of study drug ]
  Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.
• Phase 1: Changes in ECOG performance status [ Time Frame: Baseline to 30 days after last dose of study drug ]
• Phase 2: Proportion of subjects with a prostate-specific antigen decline of >50% (PSA50) at Week 12 [ Time Frame: Baseline to Week 12 ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC
• Official Title: A Phase 1/2 Study of EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With Metastatic Castration-Resistant Prostate Cancer

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: Enzalutamide
  Daily oral dose of enzalutamide
• Drug: EPI-7386 with Enzalutamide
  Daily oral dose of EPI-7386 in combination of enzalutamide

Study Arms

• Experimental: Phase 1 Cohort 1
  600 mg QD EPI-7386 in combination of Enzalutamide120 mg
  Intervention: Drug: EPI-7386 with Enzalutamide
• Experimental: Phase 1 Cohort 2
  800 mg QD EPI-7386 in combination of Enzalutamide120 mg
  Intervention: Drug: EPI-7386 with Enzalutamide
• Experimental: Phase 1 Cohort 3
  600 mg BID EPI-7386 in combination of Enzalutamide120 mg
  Intervention: Drug: EPI-7386 with Enzalutamide
• Experimental: Phase 1 Cohort 4
  RP2D mg EPI-7386 in combination of Enzalutamide160 mg
  Intervention: Drug: EPI-7386 with Enzalutamide
• Experimental: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)
  RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg
  Intervention: Drug: EPI-7386 with Enzalutamide
• Active Comparator: Phase 2 Enzalutamide single agent
  Enzalutamide 160 mg
  Intervention: Drug: Enzalutamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 7, 2021): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2026
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Karen Villaluna; 650-449-8400; kvillaluna@essapharma.com

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT05075577
• Other Study ID Numbers: EPI-7386-CS-010
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ESSA Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: ESSA Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ESSA Pharmaceuticals
• Verification Date: March 2023