Recruiting
Phase 1
Phase 2

Opevesostat

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06353386

Conditions

Prostatic Neoplasms, Castration-Resistant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Opevesostat

Olaparib

Docetaxel

Cabazitaxel

Fludrocortisone acetate

Study Details

Brief summary:

Substudy 01A is part of a larger research study that is testing experimental treatments for metastatic castration-resistant prostate cancer (mCRPC). The larger study is the umbrella study (U01).

The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC.

This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for the opevesostat-based treatment combinations. There will be no hypothesis testing in this study.

Conditions

Prostatic Neoplasms, Castration-Resistant

Study ID

NCT06353386

Start date

May 20, 2024

Status verified date

Sep, 2026

Completion date

Jan 15, 2029

Anticipated

Primary completion date

Jan 15, 2029

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:

  • Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology.
  • Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening.
  • Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy.
  • Current evidence of metastatic disease.
  • Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment.
  • Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for >4 weeks before randomization.
  • Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to <Grade 1 or baseline.
  • Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
  • 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.
  • Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

  • History of pituitary dysfunction.
  • Poorly controlled diabetes mellitus.
  • Active or unstable cardio/cerebro-vascular disease, including thromboembolic events and history of stroke or transient ischemic attack within 6 months before the first dose of study intervention, history of myocardial infarction within 6 months before the first dose of study intervention, New York Heart Association Class III or IV cardiac disease or congestive heart failure, coronary heart disease that is symptomatic, or unstable angina
  • History or family history of long corrected QT interval (QTc) syndrome.
  • Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML.
  • History or current condition of adrenal insufficiency.
  • History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.
  • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
  • Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications.
  • Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention.
  • Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization).
  • Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
  • Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids.
  • Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed.
  • Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Active autoimmune disease that has required systemic treatment in the past 2 years.
  • Active infection requiring systemic therapy.
  • Concurrent active HBV or HCV infections.

Study Design

Enrollment

220 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A1: Opevesostat

Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation.

experimental: Arm A2: Olaparib + Opevesostat

Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.

experimental: Arm A3: Docetaxel + Opevesostat

Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m\^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.

experimental: Arm A4: Cabazitaxel + Opevesostat

Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m\^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.

Interventions

Opevesostat

Oral Tablet

Olaparib

Oral Tablet

Docetaxel

IV Infusion

Cabazitaxel

IV Infusion

Fludrocortisone acetate

Oral Tablet

Dexamethasone

Oral Tablet

Prednisone

Oral Tablet

Primary outcome measure

  • Number of participants who experience one or more dose-limiting toxicities (DLTs) [ Time Frame: Up to approximately 28 days ]
  • Number of participants who experience one or more adverse events (AEs) [ Time Frame: Up to approximately 46 months ]
  • Number of participants who discontinue study intervention due to an AE [ Time Frame: Up to approximately 46 months ]
  • Prostate-specific antigen (PSA) response rate [ Time Frame: Up to approximately 46 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

UCSD Moores Cancer Center ( Site 0039)

Recruiting

La Jolla, California, United States, 92037

Contacts

Study Coordinator

858-822-6100

UCLA Hematology/Oncology - Santa Monica ( Site 0044)

Recruiting

Los Angeles, California, United States, 90404

Contacts

Study Coordinator

310-825-2631

University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051)

Recruiting

Miami, Florida, United States, 33136

Contacts

Study Coordinator

305-243-1543

University Hospitals Cleveland Medical Center ( Site 0043)

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Study Coordinator

216-844-3951

MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Study Coordinator

414-955-8296

Centre Hospitalier de l'Université de Montréal ( Site 0200)

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Study Coordinator

5148908000x27466

Jewish General Hospital ( Site 0206)

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contacts

Study Coordinator

514-340-8222

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0207)

Recruiting

Québec, Quebec, Canada, G1J 1Z4

Contacts

Study Coordinator

418-691- 5225

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 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 2026-09-03.