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Opevesostat for Metastatic Castration-Resistant Prostate Cancer

This study, called Substudy 01A, is part of a larger research effort to find new treatments for metastatic castration-resistant prostate cancer (mCRPC), a type of prostate cancer that has spread and no longer responds to hormone therapy. This substudy is testing the safety and effectiveness of a drug called opevesostat, either alone or in combination with other approved treatments like olaparib, docetaxel, or cabazitaxel. Researchers are looking at how many participants experience side effects (adverse events) and how severe they are. You may be able to join if you are 18 or older, have a confirmed diagnosis of prostate adenocarcinoma, and your cancer has progressed despite hormone therapy. The study aims to enroll 220 participants, but its current recruitment status is unclear.

Study design
This is an interventional study with two phases: a safety lead-in phase to find the right dose, and an efficacy phase. It is part of a larger umbrella study.
What's involved
Participants will receive opevesostat, either alone or in combination with other drugs. Safety will be monitored for up to approximately 46 months.
Compensation
Not stated in the trial record.
Follow-up
Participants will be followed for adverse events and discontinuations due to adverse events for up to approximately 46 months.

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NCT06353386

Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A)

Recruiting
PHASE1Ages 18+InterventionalTreatment
Merck Sharp & Dohme LLC
~220 participants
Updated 2026-05-26 on ClinicalTrials.gov
What's tested:OpevesostatOlaparibDocetaxelCabazitaxelFludrocortisone acetateDexamethasone

At a glance

Recruiting sites
70 of 77 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Number of participants who experience one or more dose-limiting toxicities (DLTs)
Measured over Up to approximately 28 days
+3 more outcomes measured

Conditions

Prostatic Neoplasms, Castration-Resistant

Explore related trials

Prostate Carcinoma

Where it's being run

77 sites across 56 states
Turkey (Türkiye)5
Quebec3
Region M. de Santiago3
Israel3
Spain3
Taiwan3
California2
Bogota D.C.2

Study leadership

  • Medical Director · STUDY_DIRECTOR · Merck Sharp & Dohme LLC

Who to contact

Toll Free Number
[email protected]
1-888-577-8839
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

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

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.

What this trial measures

  • Number of participants who experience one or more dose-limiting toxicities (DLTs)Up to approximately 28 days

    The following events, if considered drug related by the investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not laboratory value); Grade 4 hematologic toxicity lasting \>7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia associated with clinically significant bleeding); Any nonhematologic adverse event (AE) \>Grade 3 in severity should be considered a DLT (with exceptions); Any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); Febrile neutropenia Grade 3 or Grade 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 28 days due to study intervention-related toxicity; Missing \>25% of study intervention doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity.

  • Number of participants who experience one or more adverse events (AEs)Up to approximately 46 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  • Number of participants who discontinue study intervention due to an AEUp to approximately 46 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  • Prostate-specific antigen (PSA) response rateUp to approximately 46 months

    The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level will be confirmed by an additional PSA evaluation performed ≥3 weeks from the original response per Prostate Cancer Working Group (PCWG) criteria.