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Clinical Trials in the UK / NCT06136650
Recruiting Phase 3

A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)

NCT06136650 · tracked via the Priya Life Science UK tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 3
Started
2023-12-18
Last updated
2026-08-24

Condition(s) studied

Metastatic Castration-resistant Prostate Cancer (mCRPC)Prostatic Neoplasms

Investigational drug(s) / intervention(s)

OpevesostatDexamethasoneFludrocortisone acetateHydrocortisoneAbiraterone acetatePrednisone acetateEnzalutamide

Opevesostat: Administered orally

Dexamethasone: Administered orally

Fludrocortisone acetate: Administered orally

Hydrocortisone: Administered orally or IM as a rescue drug

Abiraterone acetate: Administered orally

Prednisone acetate: Administered orally

Enzalutamide: Administered orally

Study summary

The purpose of this study is to assess the efficacy and safety of opevesostat plus daily corticosteroids compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The primary study hypothesis is that opevesostat is superior to alternative abiraterone acetate or enzalutamide with respect to radiographic progression free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Blinded Independent Central Review (BICR), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology * Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening * Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography (CT)/magnetic resonance imaging (MRI) * Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) (metastatic hormone-sensitive prostate cancer \[mHSPC\] or non-metastatic hormone-sensitive prostate cancer \[nmHSPC\]), or castration-resistant prostate cancer (CRPC) (metastatic castration-resistant prostate cancer \[mCRPC\] or non-metastatic castration-resistant prostate cancer \[nmCRPC\]), for at least 8 weeks of NHA treatment (at least 14 weeks of NHA treatment for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel * Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment * Has ongoing androgen deprivation therapy (ADT) with serum testosterone \<50 ng/dL (\<1.7 nM) * Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 10 days before randomization * Has adequate organ function * Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening * Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy or ≤Grade 2 osteopenia/osteoporosis are eligible * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has presence of gastrointestinal condition * Is unable to swallow capsules/tablets * Has history of pituitary dysfunction * Has poorly controlled diabetes mellitus * Has clinically significant abnormal serum potassium or sodium level * Has any of the following at screening visit: Hypotension: systolic blood pressure (BP) \<110 mmHg, or uncontrolled hypertension: systolic BP ≥160mmHg or diastolic blood BP ≥90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive therapy * Has a history of active or unstable cardio/cerebrovascular disease, including thromboembolic events * History or family history of long QTc syndrome * Has a history of seizure(s) within 6 months before providing documented informed consent (IC) or has any condition that may predispose to seizure within 12 months prior to the date of enrollment * Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place * Has received a taxane-based chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) * Has not adequately recovered from major surgery or have ongoing surgical complications * Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures * Participants on an unstable dose of thyroid hormone therapy, as judged by the investigator, within 6 months before the start of the study intervention * Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids * Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention * Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention * Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or opevesostat * Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention * Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed * Active infection requiring systemic therapy * Has concurrent active Hepatitis B virus and Hepatitis C virus infection

Primary outcome measure(s)

Trial sites (330)

FacilityCityRegionStatus
The University of Arizona Cancer Center - North Campus ( Site 0073) Tucson Arizona Recruiting
CHAO Family Comprehensive Cancer Center and Ambulatory Care ( Site 0120) Irvine California Recruiting
UCLA Hematology/Oncology - Santa Monica ( Site 0044) Los Angeles California Recruiting
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040) Orange California Recruiting
Stanford Cancer Center ( Site 0036) Palo Alto California Recruiting
Emad Ibrahim,MD,INC. ( Site 0012) Redlands California Completed
Kaiser Permanente Riverside Medical Center ( Site 0099) Riverside California Recruiting
University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 0114) Sacramento California Recruiting
San Francisco VA Health Care System ( Site 0093) San Francisco California Recruiting
Kaiser Permanente-Kaiser Permanente, Vallejo Medical Center, Adult Oncology ( Site 0101) Vallejo California Recruiting
University of Colorado Anschutz Medical Campus ( Site 0046) Aurora Colorado Recruiting
UCHealth Highlands Ranch Hospital ( Site 0111) Highlands Ranch Colorado Recruiting
Colorado Clinical Research ( Site 0067) Lakewood Colorado Recruiting
University of Colorado Health - Lone Tree Medical Center ( Site 0112) Lone Tree Colorado Recruiting
Yale-New Haven Hospital-Yale Cancer Center ( Site 0064) New Haven Connecticut Recruiting
MedStar Washington Hospital Center ( Site 0103) Washington D.C. District of Columbia Recruiting
Florida Cancer Specialists - South ( Site 7003) Fort Myers Florida Recruiting
Mount Sinai Braman Comprehensive Cancer Center ( Site 0107) Miami Beach Florida Recruiting
Memorial Hospital West-Memorial Cancer Institute ( Site 0109) Pembroke Pines Florida Recruiting
Northside Hospital-Northside Hospital Oncology Network ( Site 0100) Atlanta Georgia Active Not Recruiting
Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0074) Elmhurst Illinois Completed
Edward-Elmhurst Healthcare, Edward Hospital-Edward Cancer Center ( Site 0075) Naperville Illinois Completed
Illinois Cancer Care ( Site 0104) Peoria Illinois Recruiting
Urology of Indiana - Carmel ( Site 0055) Carmel Indiana Recruiting
University of Kentucky Chandler Medical Center ( Site 0048) Lexington Kentucky Active Not Recruiting
Baltimore Veterans Affairs Medical Center ( Site 0069) Baltimore Maryland Recruiting
Greenebaum Comprehensive Cancer Center ( Site 0049) Baltimore Maryland Recruiting
Chesapeake Urology ( Site 0009) Towson Maryland Recruiting
Henry Ford Hospital ( Site 0015) Detroit Michigan Recruiting
Cancer and Hematology Centers of Western Michigan ( Site 0005) Grand Rapids Michigan Recruiting
Avera Cancer Institute - Marshall ( Site 0122) Marshall Minnesota Recruiting
HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0072) Saint Louis Park Minnesota Recruiting
HealthPartners Cancer Research Center-HealthPartners Cancer Center at Regions Hospital ( Site 0092) Saint Paul Minnesota Recruiting
St. Vincent Frontier Cancer Center-Research ( Site 0037) Billings Montana Recruiting
Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0026) Omaha Nebraska Recruiting
OptumCare Cancer Care-Research Department ( Site 0078) Las Vegas Nevada Recruiting
Comprehensive Cancer Centers of Nevada ( Site 0010) Las Vegas Nevada Recruiting
Rutgers Cancer Institute of New Jersey ( Site 0033) New Brunswick New Jersey Recruiting
Associated Medical Professionals - Urology ( Site 0081) Syracuse New York Recruiting
University Hospitals Cleveland Medical Center ( Site 0043) Cleveland Ohio Recruiting

+ 290 more sites — see the full list on the official registry below.

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06136650 on ClinicalTrials.gov ↗ ← All trials in the UK