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)

What this study is about

The purpose of this study is to assess the efficacy and safety of opevesostat plus hormone replacement therapy (HRT) 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.

Who can join (things the study team will check)

✅ You may be able to join if…

• 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 therapy (HRT) 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 be able to join if…

• 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

+ 8 more criteria — see the full checklist in the app.

Where this trial is running

• The University of Arizona Cancer Center - North Campus ( Site 0073), Tucson, Arizona, United States
• UCLA Hematology/Oncology - Santa Monica ( Site 0044), Los Angeles, California, United States
• University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040), Orange, California, United States
• University of California, Irvine (UCI) Health - UC Irvine Medical Center (0120), Orange, California, United States
• Stanford Cancer Center ( Site 0036), Palo Alto, California, United States
• Emad Ibrahim,MD,INC. ( Site 0012), Redlands, California, United States
• Kaiser Permanente Riverside Medical Center ( Site 0099), Riverside, California, United States
• University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 0114), Sacramento, California, United States
• San Francisco VA Health Care System ( Site 0093), San Francisco, California, United States
• Kaiser Permanente-Kaiser Permanente, Vallejo Medical Center, Adult Oncology ( Site 0101), Vallejo, California, United States
• University of Colorado Anschutz Medical Campus ( Site 0046), Aurora, Colorado, United States
• UCHealth Highlands Ranch Hospital ( Site 0111), Highlands Ranch, Colorado, United States

+ 317 more sites.

Who to contact

Toll Free Number · 1-888-577-8839 · Trialsites@msd.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06136650.