Recruiting
Phase 3

Opevesostat vs. NHA

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06136650

Conditions

Metastatic Castration-resistant Prostate Cancer (mCRPC)

Prostatic Neoplasms

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Opevesostat

Dexamethasone

Fludrocortisone acetate

Hydrocortisone

Abiraterone acetate

Study Details

Brief 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.

Conditions

Metastatic Castration-resistant Prostate Cancer (mCRPC)

Prostatic Neoplasms

Study ID

NCT06136650

Start date

Dec 18, 2023

Status verified date

Aug, 2026

Completion date

Dec 2, 2030

Anticipated

Primary completion date

May 10, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

1314 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Daily Corticosteroids + Opevesostat

Participants receive opevesostat 5 mg by oral tablets twice daily (BID) plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily (QD) continuously until disease progression. Hydrocortisone 100 mg (oral or intramuscular \[IM\]) will also be provided to participants for use as rescue medication.

active comparator: Alternative Next-Generation Hormonal Agent (NHA)

Participants receive abiraterone 1000mg QD by oral tablets plus prednisone 5 mg BID by oral tablets or enzalutamide 160 mg QD by oral tablets until disease progression.

Interventions

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

Primary outcome measure

  • Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to approximately 52 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

The University of Arizona Cancer Center - North Campus ( Site 0073)

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Study Coordinator

520-626-1068

CHAO Family Comprehensive Cancer Center and Ambulatory Care ( Site 0120)

Recruiting

Irvine, California, United States, 92612

Contacts

Study Coordinator

714-456-7890

UCLA Hematology/Oncology - Santa Monica ( Site 0044)

Recruiting

Los Angeles, California, United States, 90404

Contacts

Study Coordinator

310-210-9001

University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040)

Recruiting

Orange, California, United States, 92868

Contacts

Study Coordinator

714-456-7890

Stanford Cancer Center ( Site 0036)

Recruiting

Palo Alto, California, United States, 94304

Contacts

Study Coordinator

650-725-2078

Kaiser Permanente Riverside Medical Center ( Site 0099)

Recruiting

Riverside, California, United States, 92505

Contacts

Study Coordinator

951-353-3323

University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 0114)

Recruiting

Sacramento, California, United States, 95817

Contacts

Study Coordinator

916-734-3772

San Francisco VA Health Care System ( Site 0093)

Recruiting

San Francisco, California, United States, 94121

Contacts

Study Coordinator

415-221-4810 x23022

Kaiser Permanente-Kaiser Permanente, Vallejo Medical Center, Adult Oncology ( Site 0101)

Recruiting

Vallejo, California, United States, 94589

Contacts

Study Coordinator

707-651-1000

University of Colorado Anschutz Medical Campus ( Site 0046)

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Study Coordinator

302-290-3598

UCHealth Highlands Ranch Hospital ( Site 0111)

Recruiting

Highlands Ranch, Colorado, United States, 80129

Contacts

Study Coordinator

720-516-1000

Colorado Clinical Research ( Site 0067)

Recruiting

Lakewood, Colorado, United States, 80228

Contacts

Study Coordinator

303-885-9828

University of Colorado Health - Lone Tree Medical Center ( Site 0112)

Recruiting

Lone Tree, Colorado, United States, 80124

Contacts

Study Coordinator

720-470-9107

Yale-New Haven Hospital-Yale Cancer Center ( Site 0064)

Recruiting

New Haven, Connecticut, United States, 06510

Contacts

Study Coordinator

203-737-8076

MedStar Washington Hospital Center ( Site 0103)

Recruiting

Washington D.C., District of Columbia, United States, 20010

Contacts

Study Coordinator

202-877-6583

Florida Cancer Specialists - South ( Site 7003)

Recruiting

Fort Myers, Florida, United States, 33901

Contacts

Study Coordinator

727-364-9201

Mount Sinai Braman Comprehensive Cancer Center ( Site 0107)

Recruiting

Miami Beach, Florida, United States, 33140

Contacts

Study Coordinator

305-535-3300

Memorial Hospital West-Memorial Cancer Institute ( Site 0109)

Recruiting

Pembroke Pines, Florida, United States, 33028

Contacts

Study Coordinator

954-265-4325

Illinois Cancer Care ( Site 0104)

Recruiting

Peoria, Illinois, United States, 61615

Contacts

Study Coordinator

309-240-6388

Urology of Indiana - Carmel ( Site 0055)

Recruiting

Carmel, Indiana, United States, 46032

Contacts

Study Coordinator

317-564-5158

Baltimore Veterans Affairs Medical Center ( Site 0069)

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Study Coordinator

1-410-7074-011

Greenebaum Comprehensive Cancer Center ( Site 0049)

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Study Coordinator

410-707-4011

Chesapeake Urology ( Site 0009)

Recruiting

Towson, Maryland, United States, 21204

Contacts

Study Coordinator

410-825-5454

Henry Ford Hospital ( Site 0015)

Recruiting

Detroit, Michigan, United States, 48202

Contacts

Study Coordinator

313-916-1784

Cancer and Hematology Centers of Western Michigan ( Site 0005)

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Study Coordinator

616-399-6500

Avera Cancer Institute - Marshall ( Site 0122)

Recruiting

Marshall, Minnesota, United States, 56258

Contacts

Study Coordinator

605-601-1830

HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0072)

Recruiting

Saint Louis Park, Minnesota, United States, 55426

Contacts

Study Coordinator

952-977-5555

HealthPartners Cancer Research Center-HealthPartners Cancer Center at Regions Hospital ( Site 0092)

Recruiting

Saint Paul, Minnesota, United States, 55101

Contacts

Study Coordinator

651-254-1517

St. Vincent Frontier Cancer Center-Research ( Site 0037)

Recruiting

Billings, Montana, United States, 59102

Contacts

Study Coordinator

406-238-6685

Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0026)

Recruiting

Omaha, Nebraska, United States, 68130

Contacts

Study Coordinator

402-334-4773

OptumCare Cancer Care-Research Department ( Site 0078)

Recruiting

Las Vegas, Nevada, United States, 89102

Contacts

Study Coordinator

702-724-8787

Comprehensive Cancer Centers of Nevada ( Site 0010)

Recruiting

Las Vegas, Nevada, United States, 89148

Contacts

Study Coordinator

702-952-3449

Rutgers Cancer Institute of New Jersey ( Site 0033)

Recruiting

New Brunswick, New Jersey, United States, 08903

Contacts

Study Coordinator

732-235-2465

Associated Medical Professionals - Urology ( Site 0081)

Recruiting

Syracuse, New York, United States, 13210

Contacts

Study Coordinator

315-478-4185

University Hospitals Cleveland Medical Center ( Site 0043)

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Study Coordinator

216-844-3951

MidLantic urology ( Site 0022)

Recruiting

Bala-Cynwyd, Pennsylvania, United States, 19004

Contacts

Study Coordinator

610-667-3020

Fox Chase Cancer Center ( Site 0076)

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Contacts

Study Coordinator

267-512-1098

Ralph H. Johnson VA Health Care System (RHJVAHCS)-Urology ( Site 0083)

Recruiting

Charleston, South Carolina, United States, 29401

Contacts

Study Coordinator

843-792-7888

Avera Cancer Institute - Aberdeen ( Site 0123)

Recruiting

Aberdeen, South Dakota, United States, 57401

Contacts

Study Coordinator

605-601-1830

Avera Cancer Institute - Mitchell ( Site 0121)

Recruiting

Mitchell, South Dakota, United States, 57301

Contacts

Study Coordinator

605-601-1830

Avera Cancer Institute - Pierre ( Site 0118)

Recruiting

Pierre, South Dakota, United States, 57501

Contacts

Study Coordinator

605-224-3370

Avera Cancer Institute- Research ( Site 0094)

Recruiting

Sioux Falls, South Dakota, United States, 57105

Contacts

Study Coordinator

605-322-6900

Avera Cancer Institute - Yankton ( Site 0117)

Recruiting

Yankton, South Dakota, United States, 57078

Contacts

Study Coordinator

605-655-1800

The West Clinic, PLLC dba West Cancer Center ( Site 0063)

Recruiting

Germantown, Tennessee, United States, 38138

Contacts

Study Coordinator

901-683-0055

Texas Oncology - Central/South Texas ( Site 8003)

Recruiting

Austin, Texas, United States, 78731

Contacts

Study Coordinator

512-427-9400

Texas Oncology - DFW ( Site 8001)

Recruiting

Dallas, Texas, United States, 75246

Contacts

Study Coordinator

214-370-1000

Texas Oncology - Gulf Coast ( Site 8002)

Recruiting

Houston, Texas, United States, 77024

Contacts

Study Coordinator

713-467-1722

University of Virginia Health System ( Site 0054)

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Study Coordinator

434-327-3029

Inova Schar Cancer Institute ( Site 0017)

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Study Coordinator

571-472-4724

Virginia Cancer Specialists (VCS) ( Site 8004)

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Study Coordinator

844-482-4812

VCU Health Adult Outpatient Pavillion ( Site 0061)

Recruiting

Richmond, Virginia, United States, 23219

Contacts

Study Coordinator

804-628-6430

Blue Ridge Cancer Care ( Site 0004)

Recruiting

Roanoke, Virginia, United States, 24014

Contacts

Study Coordinator

540-982-0237

Spokane Urology ( Site 0035)

Recruiting

Spokane, Washington, United States, 99202

Contacts

Study Coordinator

509-747-3147

Northwest Cancer Specialists (Compass Oncology) ( Site 8008)

Recruiting

Vancouver, Washington, United States, 98684

Contacts

Study Coordinator

971-708-7600

Medical College of Wisconsin ( Site 0020)

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Study Coordinator

414-805-6700

Cross Cancer Institute ( Site 0281)

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Contacts

Study Coordinator

780-432-8771

BC Cancer Abbotsford-Clinical Trials Unit ( Site 0287)

Recruiting

Abbotsford British Columbia, British Columbia, Canada, V2S 0C2

Contacts

Study Coordinator

604-851-4710 x645274

Trillium Health Partners - Credit Valley Hospital ( Site 0289)

Recruiting

Mississauga, Ontario, Canada, L5M 2N1

Contacts

Study Coordinator

9058134299

The Ottawa Hospital - General Campus ( Site 0286)

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contacts

Study Coordinator

613-737-7700

Sunnybrook Research Institute ( Site 0285)

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Study Coordinator

416-480-5000

Centre Hospitalier de l'Université de Montréal ( Site 0276)

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Study Coordinator

514 890 8000 x 27466

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0277)

Recruiting

Québec, Quebec, Canada, G1J 1Z4

Contacts

Study Coordinator

418-525-4444

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-24.