Open Actively Recruiting

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)

About

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 hypotheses are 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) and overall survival (OS), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 3

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

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 current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography scan (CT)/magnetic resonance imaging (MRI)
Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening
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), for at least 8 weeks (at least 14 weeks 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 six cycles of docetaxel and had no radiographic disease progression while receiving docetaxel
Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization
Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
Has had prior treatment with Poly polymerase inhibitors (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
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 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 a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events
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
History or family history of long QTc syndrome
Has a history of seizure(s) within 6 months prior to signing the 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 and or NHA for metastatic castration-resistant prostate cancer (mCRPC)
Has not adequately recovered from major surgery or have ongoing surgical complications
Has received prior treatment with radium for prostate cancer
Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures
Participants on an unstable dose of thyroid hormone therapy 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

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Study Stats

Protocol No.

23-001835