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 now · Phase 3

Conditions studied: Metastatic Castration-resistant Prostate Cancer (mCRPC), Prostatic Neoplasms

In brief

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.

Key facts

Study ID

NCT06136650

Run by

Merck Sharp & Dohme LLC

People needed

1314

Starts

2023-12-18

Expected to finish

2030-12-02

Last updated by the study team

2026-07-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• 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

Where it is running

• Baltimore Veterans Affairs Medical Center ( Site 0069) — Baltimore, Maryland, United States (enrolling)
• Greenebaum Comprehensive Cancer Center ( Site 0049) — Baltimore, Maryland, United States (enrolling)
• UCLA Hematology/Oncology - Santa Monica ( Site 0044) — Los Angeles, California, United States (enrolling)
• Stanford Cancer Center ( Site 0036) — Palo Alto, California, United States (enrolling)
• The University of Arizona Cancer Center - North Campus ( Site 0073) — Tucson, Arizona, United States (enrolling)
• Kaiser Permanente Riverside Medical Center ( Site 0099) — Riverside, California, United States (enrolling)
• University of California, Irvine (UCI) Health - UC Irvine Medical Center (0120) — Orange, California, United States (enrolling)
• San Francisco VA Health Care System ( Site 0093) — San Francisco, California, United States (enrolling)
• Kaiser Permanente-Kaiser Permanente, Vallejo Medical Center, Adult Oncology ( Site 0101) — Vallejo, California, United States (enrolling)
• University of Colorado Anschutz Medical Campus ( Site 0046) — Aurora, Colorado, United States (enrolling)
• University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040) — Orange, California, United States (enrolling)
• Colorado Clinical Research ( Site 0067) — Lakewood, Colorado, United States (enrolling)
• University of Colorado Health - Lone Tree Medical Center ( Site 0112) — Lone Tree, Colorado, United States (enrolling)
• Yale-New Haven Hospital-Yale Cancer Center ( Site 0064) — New Haven, Connecticut, United States (enrolling)
• MedStar Washington Hospital Center ( Site 0103) — Washington D.C., District of Columbia, United States (enrolling)
• University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 0114) — Sacramento, California, United States (enrolling)
• Mount Sinai Cancer Center ( Site 0107) — Miami Beach, Florida, United States (enrolling)
• Memorial Hospital West-Memorial Cancer Institute ( Site 0109) — Pembroke Pines, Florida, United States (enrolling)
• Northside Hospital-Northside Hospital Oncology Network ( Site 0100) — Atlanta, Georgia, United States (enrolling)
• Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0074) — Elmhurst, Illinois, United States (enrolling)
• Edward-Elmhurst Healthcare, Edward Hospital-Edward Cancer Center ( Site 0075) — Naperville, Illinois, United States (enrolling)
• Illinois Cancer Care ( Site 0104) — Peoria, Illinois, United States (enrolling)
• Urology of Indiana - Carmel ( Site 0055) — Carmel, Indiana, United States (enrolling)
• UCHealth Highlands Ranch Hospital ( Site 0111) — Highlands Ranch, Colorado, United States (enrolling)
• Chesapeake Urology ( Site 0009) — Towson, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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