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)
| NCT ID | NCT06136650 |
| Status | Recruiting |
| Phase | Phase 3 |
| Sponsor | Merck Sharp & Dohme LLC |
| Condition | Metastatic Castration-resistant Prostate Cancer (mCRPC) |
| Study Type | INTERVENTIONAL |
| Enrollment | 1,314 participants |
| Start Date | 2023-12-18 |
| Primary Completion | 2028-05-10 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.
This trial targets 1,314 participants in total. It began in 2023-12-18 with a primary completion date of 2028-05-10.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
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.
Eligibility Criteria
Inclusion Criteria: 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 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) Exclusion Criteria: 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 * 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
Contact & Investigator
Medical Director
STUDY DIRECTOR
Merck Sharp & Dohme LLC
Frequently Asked Questions
Who can join the NCT06136650 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Metastatic Castration-resistant Prostate Cancer (mCRPC). Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT06136650 trial and what does that mean for participants?
Phase 3 trials are large-scale studies comparing the new treatment to existing standards of care or a placebo. They provide the evidence needed for regulatory approval. This trial targets 1,314 participants.
Is NCT06136650 currently recruiting?
Yes, NCT06136650 is actively recruiting participants. Contact the research team at Trialsites@msd.com for enrollment information.
Where is the NCT06136650 trial being conducted?
This trial is being conducted at Tucson, United States, Los Angeles, United States, Orange, United States, Orange, United States and 11 additional locations.
Who is sponsoring the NCT06136650 clinical trial?
NCT06136650 is sponsored by Merck Sharp & Dohme LLC. The principal investigator is Medical Director at Merck Sharp & Dohme LLC. The trial plans to enroll 1,314 participants.
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