Study

Overview

Official Title: MK-5684-004: A Phase 3, Randomized, Open-label Study of Opevesostat Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) That Progressed On or After Prior Treatment with One Next-generation Hormonal Agent (NHA) (OMAHA-004)

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.

Study Type:

Interventional

Study Phase:

Phase 3

Estimated Enrollment:

1314

Study Start Date:

December 2023

Estimated Study Completion Date:

December 2030

Estimated Primary Completion Date:

May 2028

Eligibility

Ages Eligible for Study:

18 years and older

Genders Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

United States Toll Free Number 1-800-770-4674

Ponce, 00717
San Juan, 00909
Tucson, Arizona, 85719
Los Angeles, California, 90404
Orange, California, 92868
Orange, California, 92868
Palo Alto, California, 94304
Riverside, California, 92505
Sacramento, California, 95817
San Francisco, California, 94121
Vallejo, California, 94589
Aurora, Colorado, 80045
Highlands Ranch, Colorado, 80129
Lakewood, Colorado, 80228
Lone Tree, Colorado, 80124
New Haven, Connecticut, 06510
Washington, District of Columbia, 20010
Miami Beach, Florida, 33140
Pembroke Pines, Florida, 33028
Atlanta, Georgia, 30342
Elmhurst, Illinois, 60126
Naperville, Illinois, 60540
Peoria, Illinois, 61615
Carmel, Indiana, 46032
Baltimore, Maryland, 21201
Baltimore, Maryland, 21201
Towson, Maryland, 21204
Detroit, Michigan, 48202
Grand Rapids, Michigan, 49503
Marshall, Minnesota, 56258
Saint Louis Park, Minnesota, 55426
Saint Paul, Minnesota, 55101
Billings, Montana, 59102
Omaha, Nebraska, 68130
Las Vegas, Nevada, 89102
Las Vegas, Nevada, 89148
New Brunswick, New Jersey, 08901
Syracuse, New York, 13210
Cleveland, Ohio, 44106
Zanesville, Ohio, 43701
Bala Cynwyd, Pennsylvania, 19004
Philadelphia, Pennsylvania, 19111
Charleston, South Carolina, 29401
Aberdeen, South Dakota, 57401
Mitchell, South Dakota, 57301
Sioux Falls, South Dakota, 57105
Yankton, South Dakota, 57078
Germantown, Tennessee, 38138
Austin, Texas, 78731
Dallas, Texas, 75246
Houston, Texas, 77024
Charlottesville, Virginia, 22908
Fairfax, Virginia, 22031
Fairfax, Virginia, 22031
Richmond, Virginia, 23219
Roanoke, Virginia, 24014
Spokane, Washington, 99202
Vancouver, Washington, 98684
MILWAUKEE, Wisconsin, 53226

Canada Study Coordinator 613-737-7700

Results

No Study Results Posted

Study Detail

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)

Overview

Eligibility

CRITERIA

Locations

Results