Study of Opevesostat for Metastatic Castration-Resistant Prostate Cancer
This study is testing a new medication called opevesostat, given with daily corticosteroids (like dexamethasone or fludrocortisone), for men with metastatic castration-resistant prostate cancer (mCRPC). This is prostate cancer that has spread and is no longer responding to standard hormone therapy. You might be able to join if you've already received one type of next-generation hormone agent. Researchers want to see if opevesostat is better than other common treatments (abiraterone acetate or enzalutamide) at stopping the cancer from growing or spreading, which is called radiographic progression-free survival (rPFS). The study is looking for about 1314 participants.
- Study design
- This interventional study is comparing opevesostat with other standard treatments. It plans to enroll 1314 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for radiographic progression-free survival for up to approximately 52 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06136650
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)
Recruiting
PHASE3Ages 18+InterventionalTreatmentMerck Sharp & Dohme LLC
~1,314 participants
Updated 2026-08-24 on ClinicalTrials.gov
What's tested:OpevesostatDexamethasoneFludrocortisone acetateHydrocortisoneAbiraterone acetatePrednisone acetate
At a glance
Recruiting sites
301 of 330 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Radiographic Progression-Free Survival (rPFS)
Measured over Up to approximately 52 months
Conditions
Where it's being run
330 sites across 183 statesJapan11
California9
Turkey (Türkiye)9
Israel8
Taiwan6
South Dakota5
Virginia5
Guatemala5
Study leadership
- Medical Director · STUDY_DIRECTOR · Merck Sharp & Dohme LLC
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
What this trial measures
- Radiographic Progression-Free Survival (rPFS)Up to approximately 52 months
rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.