Combining EPI-7386 With Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer

NCT06312670 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CASE2823
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer. The main goals of this study are to evaluate the antitumor activity of EPI-7386 in combination with enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC), and to evaluate the pharmacokinetics (PK) of EPI-7386 when dosed in combination with enzalutamide. Participants will will take the study drug, EPI-7360, twice a day by mouth and enzalutamide once a day by mouth, alongside clinic visits every two weeks.

Conditions

Metastatic Hormone-sensitive Prostate Cancer (mHSPC); Prostate Cancer; Prostate Adenocarcinoma

Keywords

Metastatic Hormone-sensitive Prostate Cancer (mHSPC); Prostate Cancer; Androgen Deprivation Therapy; Prostate adenocarcinoma; Recurrent metastatic

Outcome Measures

Primary Outcomes (4)

• Biochemical response rate

  Defined as prostate-specific antigen (PSA) undetectable (\<0.2 ng/mL) at 6 months after treatment. The true BRR for the study population will be estimated based on the number of biochemical responses using a binomial distribution, and its confidence interval (CI) will be estimated using Wilson's method.

  Post-intervention at Week 4

• PSA progesterone-free survival (PFS)

  Progression free survival (PFS) is measured from the date of the start of the treatment to the date of progression or death and is censored at the date of last followed for those that have not progressed

  Post-intervention at Week 4

• Radiographic PFS (rPFS)

  Progression free survival (PFS) is measured from the date of the start of the treatment to the date of progression or death and is censored at the date of last followed for those that have not progressed

  Post-intervention at Week 4

• ORR (confirmed)

  Objective response rate (ORR)

  Post-intervention at Week 4

Secondary Outcomes (12)

• AUC0-24

  Beginning of treatment day 1, at week 2, week 4, week 6

• Maximum concentration (Cmax)

  Beginning of treatment day 1, at week 2, week 4, week 6

• Predose Plasma Concentration

  Beginning of treatment day 1, at week 2, week 4, week 6

• Time to reach Cmax (Tmax)

  Beginning of treatment day 1, at week 2, week 4, week 6

• Terminal elimination half-life

  Beginning of treatment day 1, at week 2, week 4, week 6

Study Arms (1)

EPI-7386 + Enzalutamide

EXPERIMENTAL

EPI-7386 at 600 mg twice daily orally with standard of care Enzalutamide at 160 mg, once daily, orally for 36 months of treatment (11 cycles).

Drug: EPI-7386; Drug: Enzalutamide; Drug: Androgen Deprivation Therapy (ADT)

Interventions

EPI-7386 DRUG

600 mg orally administered twice daily

EPI-7386 + Enzalutamide

Enzalutamide DRUG

160 mg administered orally once daily, with or without food

EPI-7386 + Enzalutamide

Androgen Deprivation Therapy (ADT) DRUG

LHRH agonist/antagonist or orchiectomy

EPI-7386 + Enzalutamide

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed prostate adenocarcinoma without small cell or neuroendocrine features (please note: \>10% small cell or neuroendocrine differentiation will be excluded).
• Subjects must have received no prior second-generation antiandrogen therapies for this disease. Androgen deprivation with LHRH agonist/antagonist therapy or history of bilateral orchiectomy that started less than 12 weeks before study enrollment is allowed.
• Subjects may have either de novo or recurrent metastatic disease. Presence of metastatic disease at study entry documented by 1 or more lesions - bone, lymph node, soft tissue, or visceral metastases - observed by any imaging technique.
• Age \>18 years. This study will be limited to adults only.
• Evidence of metastatic disease by conventional CT of chest, abdomen, and pelvis, and bone scans, OR Positron emission tomography (PET) scan, OR MRI.
• ECOG performance status of 0 to 2.
• Subjects must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>1000/μL; platelet count \>100 000/μL; hemoglobin \>8.5 g/dL) at screening. Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening).
• Total bilirubin (TBIL) \<2 × the upper limit of normal (ULN) at screening, except subjects with documented Gilbert syndrome who must have a TBIL \<3 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<5 × ULN at screening
• Creatinine clearance ≥45 mL/min and/or estimated glomerular filtration rate (eGFR) ≥30
• Albumin \>30 g/L (3.0 g/dL) at screening
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days before the start of study treatment.
• Radiation therapy is allowed at any time, as deemed appropriate by the treating investigator.
• Subjects of child-producing potential agree to use highly effective contraceptive methods (i.e., barrier contraception measures such as a male condom with spermicide during intercourse) and avoid sperm donation during the study treatment and for 3 months after the last dose of study treatment. A man is considered to be of child-producing potential, unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. Partners of participants must also practice approved forms of birth control.

You may not qualify if:

• Evidence of mCRPC.
• Receipt of any other investigational agents.
• 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 noninvasive malignancies, as determined by the PI or CoPI.
• Gastrointestinal issues affecting absorption (e.g., gastrectomy).
• Known history of seizure or conditions that may predispose the subject to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, or brain arteriovenous malformation. Subjects with brain metastases/central nervous system (CNS) disease that are treated prior to enrollment will be allowed in this clinical trial.
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
• Use of compounds known to be strong inducers of CYP3A within 30 days prior to start of study drug treatment, and strong inhibitors of CYP2C8 within 14 days of the first dose of study treatment.
• Use of narrow therapeutic index sensitive CYP2C8 substrates (e.g., daprobustat, dasabuvir, repaglinide, paclitaxel) or sensitive substrates for CYP3A.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations considered by the Investigator to limit compliance with study requirements.

Sponsors & Collaborators

• Pedro Barata, MD, MSc: lead
• ESSA Pharma Inc.: collaborator

Study Sites (2)

University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• Jang A, Fowler P, Helminiak K, Kumar HLS, Pasucal J, Delong V, Zhong JY, Jindal T, Grier AL, Patel RR, Hislop M, Cesano A, Villaluna K, Younginger B, Wolff K, Richey K, Bray J, Garcia H, Adamowicz T, Reese A, Nizam A, Gupta S, Wee CE, Margevicius S, Fu P, Mendiratta P, Sheng IY, Brown JR, Garcia JA, Barata PC. EXTRA-PC: A phase II trial of masofaniten (EPI-7386) and enzalutamide for patients with treatment-naive metastatic hormone-sensitive prostate cancer. Oncologist. 2025 Dec 30:oyaf434. doi: 10.1093/oncolo/oyaf434. Online ahead of print.

  PMID: 41467749 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

enzalutamide; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Pedro Barata, MD, MSc

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Christopher Wee, MD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Clinical Genitourinary Medical Oncology Research Program, Prinicipal Investigator

Model Details: Phase 2, single-arm study composed of 2 stages: in the first stage, 13 subjects diagnosed with mHSPC will be enrolled and treated with EPI-7386 in combination with enzalutamide. If there are 8 or less subjects with a biochemical response at 6 months, then the trial will be suspended. Otherwise, 22 additional subjects will be enrolled and treated.

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: March 15, 2024
• Study Start: May 16, 2024
• Primary Completion: January 9, 2025
• Study Completion: January 9, 2025
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Compiled and analyzed participant data will be published upon study completion.
• Access Criteria: Link to be provided at time of article publication.

Locations

US (2)