Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)

Purpose

This is a phase 3, randomized, open-label study of opevesostat compared to alternative abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer (mCRPC) with respect to overall survival (OS) in participants with mCRPC previously treated with next-generation hormonal agent (NHA) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior with respect to OS in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.

Condition

  • Prostate Cancer Metastatic

Eligibility

Eligible Ages
All ages
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology. - Has prostate cancer progression while on androgen deprivation therapy (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 by computed tomography/magnetic resonance imaging (CT/MRI). - Has disease that progressed during or after treatment with 1 novel hormonal agent (NHA) - Has received 1 but no more than 2 taxane-based chemotherapy regimens for metastatic castration-resistant prostate cancer (mCRPC) and has had progressive disease (PD) during or after treatment - Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM) - Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated - Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization - Has had prior treatment with PARPi or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment - Has received prior 177Lu-PSMA-617 or were deemed ineligible to receive 177Lu-PSMA-617 treatment by the investigator or refused 177Lu-PSMA-617 treatment - Participants who have not received cabazitaxel can be enrolled if they are ineligible for cabazitaxel treatment as determined by the investigator or have refused treatment - If participant received first generation anti-androgen therapy before screening, the participant has evidence of disease progression >4 weeks since the last flutamide treatment and >6 weeks since the last bicalutamide or nilutamide treatment - Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥ 4 weeks before the date of randomization - Participants with human immunodeficiency virus (HIV) infection must have well controlled HIV on antiretroviral therapy (ART) - 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 can produce sperm must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat, for at least 30 days after the last dose of abiraterone acetate, and for at least 3 months after the last dose of enzalutamide: EITHER be abstinent OR must agree to use male condom

Exclusion Criteria

  • Has a gastrointestinal disorder that might affect absorption - Has a history of pituitary dysfunction - Has poorly controlled diabetes mellitus - Has clinically significant abnormal serum potassium or sodium level - Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events - Has a history of seizure within 6 months of providing documented informed consent or any condition that may predispose to seizures within 12 months before the date of randomization - Has a history of clinically significant ventricular arrhythmias - Has received an anticancer monoclonal antibody (mAb) within 4 weeks before the date of randomization, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of randomization - Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications - Participants who have not adequately recovered from major surgery or have ongoing surgical complications - Has used herbal or medicinal products that may have hormonal anti-prostate cancer activity and/or are known to decrease prostate-specific Antigen (PSA) (eg, saw palmetto, megesterol acetate, citrus pectin polysaccharide) within 4 weeks before the date of randomization - Has received radium-223 or lutetium-177 within 4 weeks before the date of randomization, or has not recovered to Grade ≤1 or baseline from AEs due to radium-223 or lutetium-177 administered more than 4 weeks before the date of randomization - Has received treatment with 5-αreductase inhibitors (eg, finasteride or dutasteride), estrogens, or cyproterone within 4 weeks before the date of randomization - Has received colony-stimulating factors within 28 days before the date of randomization - Has received a whole blood transfusion in the last 120 days before the date of randomization. Packed red blood cells and platelet transfusions are acceptable if not given within 28 days of the date of randomization - Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention as follows: enzalutamide or apalutamide within 3 weeks or abiraterone acetate + prednisone or darolutamide within 2 weeks - Has a "superscan" bone scan - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication - Has a known additional malignancy that is progressing or has required active treatment within the past 3 years - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Has an active autoimmune disease that has required systemic treatment in past 2 years - Has an active infection requiring systemic therapy - Has concurrent active HBV or known active HCV infection - Has a history of long QTc syndrome - Has any of the following at Screening Visit: hypotension (systolic BP <110 mm Hg) or uncontrolled hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥90 mm Hg, in 2 out of 3 recordings with optimized antihypertensive therapy) - Is unable to swallow capsules/tablets - Is currently being treated with cytochrome 450-inducing antiepileptic drugs for seizures - Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention - Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention - Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids - Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention - Systemic use of the following medications within 2 weeks before the first dose of study intervention: strong CYP3A4 inducers (eg, avasimibe, carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, or St John's Wort); P-gp inhibitors (eg, erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvir-sofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, or milk thistle [Silybum marianum]) - Use of aldosterone antagonist (eg, spironolactone, eplerenone) and phenytoin within 4 weeks before the start of the study intervention

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Opevesostat 		Participants receive opevesostat 5 mg by oral tablets twice daily (bid) plus dexamethasone 1.5 mg by oral tablets once daily (qd) and 0.1 mg fludrocortisone acetate by oral tablet qd until progression. Hydrocortisone 100 mg (oral or intramuscular [IM]) dose will also be provided to participants for use as rescue medication.
  • Drug: Opevesostat
    Administered orally
    Other names:
    • MK-5684
  • Drug: Hydrocortisone
    Administered orally or IM as a rescue medication
  • Drug: Fludrocortisone acetate
    Administered orally
  • Drug: Dexamethasone
    Administered orally as rescue medication
Active Comparator
Abiraterone Acetate or Enzalutamide 		Participants receive abiraterone 1000 mg qd by oral tablets plus prednisone 5 mg bid by oral tablets or enzalutamide 160 mg qd by oral tablets.
  • Drug: Abiraterone acetate
    Administered orally
    Other names:
    • ZYTIGA
    • YONSA
  • Drug: Enzalutamide
    Administered orally
    Other names:
    • XTANDI
  • Drug: Prednisone
    Administered orally

Recruiting Locations

Stanford Cancer Center ( Site 0036)
Palo Alto 5380748, California 5332921 94304
Contact:
Study Coordinator
650-725-2078

Kaiser Permanente Riverside Medical Center ( Site 0099)
Riverside 5387877, California 5332921 92505
Contact:
Study Coordinator
951-809-8361

Anschutz Cancer Pavilion ( Site 0046)
Aurora 5412347, Colorado 5417618 80045
Contact:
Study Coordinator
302-290-3598

University of Colorado Health - Highlands Ranch Hospital ( Site 0111)
Highlands Ranch 5425043, Colorado 5417618 80129
Contact:
Study Coordinator
302-290-3598

University of Colorado Health - Lone Tree Medical Center ( Site 0112)
Lone Tree 5429208, Colorado 5417618 80124
Contact:
Study Coordinator
720-848-5146

Yale-New Haven Hospital-Yale Cancer Center ( Site 0064)
New Haven 4839366, Connecticut 4831725 06510
Contact:
Study Coordinator
203-737-8076

Florida Cancer Specialists - South ( Site 7003)
Fort Myers 4155995, Florida 4155751 33901
Contact:
Study Coordinator
727-364-9201

University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0051)
Miami 4164138, Florida 4155751 33136
Contact:
Study Coordinator
305-243-1543

University of Illinois at Chicago ( Site 0105)
Chicago 4887398, Illinois 4896861 60612
Contact:
Study Coordinator
973-330-2391

University of Chicago Medical Center ( Site 0045)
Chicago 4887398, Illinois 4896861 60637
Contact:
Study Coordinator
773-702-7609

University of Iowa ( Site 0047)
Iowa City 4862034, Iowa 4862182 52242
Contact:
Study Coordinator
319-353-8155

Baltimore Veterans Affairs Medical Center ( Site 0069)
Baltimore 4347778, Maryland 4361885 21201
Contact:
Study Coordinator
410-707-4011

Greenebaum Comprehensive Cancer Center ( Site 0049)
Baltimore 4347778, Maryland 4361885 21201
Contact:
Study Coordinator
410-707-4011

M Health Fairview Clinics and Surgery Center ( Site 0019)
Minneapolis 5037649, Minnesota 5037779 55455
Contact:
Study Coordinator
612-626-1422

Metro-Minnesota Community Clinical Oncology ( Site 0014)
Saint Louis Park 5045021, Minnesota 5037779 55416
Contact:
Study Coordinator
952-993-3252

University Of Nebraska Medical Center-Oncology/Hematology ( Site 0095)
Omaha 5074472, Nebraska 5073708 68105
Contact:
Study Coordinator
402-559-8500

Comprehensive Cancer Centers of Nevada ( Site 0010)
Las Vegas 5506956, Nevada 5509151 89148
Contact:
Study Coordinator
702-952-1251

Atlantic Health System Morristown Medical Center ( Site 0115)
Morristown 5101427, New Jersey 5101760 07960
Contact:
Study Coordinator
973-971-7960

James J. Peters VA Medical Center ( Site 0088)
The Bronx 5110266, New York 5128638 10468
Contact:
Study Coordinator
718-584-9000

University Hospitals Cleveland Medical Center ( Site 0043)
Cleveland 5150529, Ohio 5165418 44106
Contact:
Study Coordinator
216-844-3951

VA Portland Health Care System ( Site 0058)
Portland 5746545, Oregon 5744337 97239
Contact:
Study Coordinator
503-220-8262

Avera Cancer Institute - Pierre ( Site 0118)
Pierre 5767918, South Dakota 5769223 57501
Contact:
Study Coordinator
605-224-3370

Avera Cancer Institute- Research ( Site 0094)
Sioux Falls 5231851, South Dakota 5769223 57105
Contact:
Study Coordinator
605-322-6900

Avera Cancer Institute - Yankton ( Site 0117)
Yankton 5233053, South Dakota 5769223 57078
Contact:
Study Coordinator
605-655-1800

SCRI Oncology Partners ( Site 7000)
Nashville 4644585, Tennessee 4662168 37203
Contact:
Study Coordinator
615-218-4647

Texas Oncology - Central/South Texas ( Site 8003)
Austin 4671654, Texas 4736286 78731
Contact:
Study Coordinator
512-427-9400

Texas Oncology - Gulf Coast ( Site 8002)
The Woodlands 4736476, Texas 4736286 77380
Contact:
Study Coordinator
713-467-1722

University of Virginia Health System ( Site 0054)
Charlottesville 4752031, Virginia 6254928 22908
Contact:
Study Coordinator
434-327-3029

Blue Ridge Cancer Care ( Site 0004)
Roanoke 4782167, Virginia 6254928 24014
Contact:
Study Coordinator
540-982-0237

Fred Hutchinson Cancer Center ( Site 0013)
Seattle 5809844, Washington 5815135 98109
Contact:
Study Coordinator
617-413-9079

MEDICAL COLLEGE OF WISCONSIN ( Site 0020)
Milwaukee 5263045, Wisconsin 5279468 53226
Contact:
Study Coordinator
414-805-4600

Ad-Vance Medical Research-Research ( Site 1353)
Ponce 4566880, Puerto Rico 00717
Contact:
Study Coordinator
787-651-6697

More Details

NCT ID
NCT06136624
Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

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

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