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RECRUITING

NCT06136624

PHASE3

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

Sponsor: Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

Summary

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.

Official title: A Phase 3 Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Previously Treated With Next-generation Hormonal Agent (NHA) and Taxane-based Chemotherapy (OMAHA-003)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

1310

Start Date

2023-12-31

Completion Date

2030-02-15

Last Updated

2026-11-03

Healthy Volunteers

Conditions

Prostate Cancer Metastatic

Interventions

DRUG

Opevesostat

Administered orally

DRUG

Abiraterone acetate

Administered orally

DRUG

Enzalutamide

Administered orally

DRUG

Hydrocortisone

Administered orally or IM as a rescue medication

DRUG

Fludrocortisone acetate

Administered orally

DRUG

Prednisone

Administered orally as a rescue medication

DRUG

Dexamethasone

Administered orally as rescue medication

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

Locations (288)

University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040)

Orange, California, United States

Stanford Cancer Center ( Site 0036)

Palo Alto, California, United States

Kaiser Permanente Riverside Medical Center ( Site 0099)

Riverside, California, United States

Anschutz Cancer Pavilion ( Site 0046)

Aurora, Colorado, United States

University of Colorado Health - Highlands Ranch Hospital ( Site 0111)

Highlands Ranch, Colorado, United States

Colorado Clinical Research ( Site 0067)

Lakewood, Colorado, United States

University of Colorado Health - Lone Tree Medical Center ( Site 0112)

Lone Tree, Colorado, United States

Yale-New Haven Hospital-Yale Cancer Center ( Site 0064)

New Haven, Connecticut, United States

Florida Cancer Specialists - South ( Site 7003)

Fort Myers, Florida, United States

Bruce W. Carter Veterans Affairs Medical Center ( Site 0082)

Miami, Florida, United States

University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0051)

Miami, Florida, United States

University of Illinois at Chicago ( Site 0105)

Chicago, Illinois, United States

University of Chicago Medical Center ( Site 0045)

Chicago, Illinois, United States

University of Iowa ( Site 0047)

Iowa City, Iowa, United States

University of Kentucky Chandler Medical Center ( Site 0048)

Lexington, Kentucky, United States

Ochsner Clinic Foundation ( Site 0108)

New Orleans, Louisiana, United States

Baltimore Veterans Affairs Medical Center ( Site 0069)

Baltimore, Maryland, United States

Greenebaum Comprehensive Cancer Center ( Site 0049)

Baltimore, Maryland, United States

Henry Ford Hospital ( Site 0015)

Detroit, Michigan, United States

Avera Cancer Institute - Marshall ( Site 0122)

Marshall, Minnesota, United States

M Health Fairview Clinics and Surgery Center ( Site 0019)

Minneapolis, Minnesota, United States

Metro-Minnesota Community Clinical Oncology ( Site 0014)

Saint Louis Park, Minnesota, United States

Hattiesburg Clinic Hematology/Oncology ( Site 0120)

Hattiesburg, Mississippi, United States

Washington University School of Medicine-Internal Medicine/Oncology ( Site 0062)

St Louis, Missouri, United States

University Of Nebraska Medical Center-Oncology/Hematology ( Site 0095)

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada ( Site 0010)

Las Vegas, Nevada, United States

Atlantic Health System Morristown Medical Center ( Site 0115)

Morristown, New Jersey, United States

Rutgers Cancer Institute of New Jersey ( Site 0033)

New Brunswick, New Jersey, United States

James J. Peters VA Medical Center ( Site 0088)

The Bronx, New York, United States

University Hospitals Cleveland Medical Center ( Site 0043)

Cleveland, Ohio, United States

Oregon Health and Science University ( Site 0028)

Portland, Oregon, United States

VA Portland Health Care System ( Site 0058)

Portland, Oregon, United States

AHN Allegheny General Hospital ( Site 0001)

Pittsburgh, Pennsylvania, United States

Ralph H. Johnson VA Health Care System (RHJVAHCS)-Urology ( Site 0083)

Charleston, South Carolina, United States

Avera Cancer Institute - Aberdeen ( Site 0123)

Aberdeen, South Dakota, United States

Avera Cancer Institute - Mitchell ( Site 0121)

Mitchell, South Dakota, United States

Avera Cancer Institute - Pierre ( Site 0118)

Pierre, South Dakota, United States

Avera Cancer Institute- Research ( Site 0094)

Sioux Falls, South Dakota, United States

Avera Cancer Institute - Yankton ( Site 0117)

Yankton, South Dakota, United States

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, United States

Texas Oncology - Central/South Texas ( Site 8003)

Austin, Texas, United States

Texas Oncology - DFW ( Site 8001)

Dallas, Texas, United States

Texas Oncology - Gulf Coast ( Site 8002)

Houston, Texas, United States

University of Virginia Health System ( Site 0054)

Charlottesville, Virginia, United States

VCU Health Adult Outpatient Pavillion ( Site 0061)

Richmond, Virginia, United States

Blue Ridge Cancer Care ( Site 0004)

Roanoke, Virginia, United States

Fred Hutchinson Cancer Center ( Site 0013)

Seattle, Washington, United States

Medical College of Wisconsin ( Site 0020)

Milwaukee, Wisconsin, United States

Hospital Británico de Buenos Aires-Oncology ( Site 0202)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Instituto de Investigaciones Clínicas Mar del Plata ( Site 0201)

Mar del Plata, Buenos Aires, Argentina

Asociación de Beneficencia Hospital Sirio Libanés ( Site 0205)

Buenos Aires, Buenos Aires F.D., Argentina

Instituto Alexander Fleming-Alexander Fleming ( Site 0206)

Buenos Aires, Buenos Aires F.D., Argentina

Sanatorio Parque ( Site 0208)

Rosario, Santa Fe Province, Argentina

Hospital Aleman-Oncology ( Site 0207)

Buenos Aires, Argentina

Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 0204)

Mendoza, Argentina

Dubbo Hospital ( Site 0235)

Dubbo, New South Wales, Australia

Macquarie University-MQ Health Clinical Trials Unit ( Site 0234)

Macquarie University, New South Wales, Australia

Westmead Hospital ( Site 0232)

Westmead, New South Wales, Australia

Princess Alexandra Hospital-Cancer Care Serices ( Site 0237)

Brisbane, Queensland, Australia

Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0230)

Melbourne, Victoria, Australia

Medizinische Universität Graz-Innere Medizin Klin. Abt. Onkologie ( Site 0280)

Graz, Styria, Austria

Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 0276)

Linz, Upper Austria, Austria

Klinikum Wels-Grieskirchen GmbH ( Site 0279)

Wels, Upper Austria, Austria

Hospital Santa Rita de Cassia-Centro de Pesquisa Clínica ( Site 0320)

Vitória, Espírito Santo, Brazil

Obras Sociais Irma Dulce ( Site 0302)

Salvador, Estado de Bahia, Brazil

Hospital Felicio Rocho ( Site 0317)

Belo Horizonte, Minas Gerais, Brazil

Hospital Mario Penna ( Site 0309)

Belo Horizonte, Minas Gerais, Brazil

Hospital Universitário Evangélico Mackenzie-Centro de Oncologia Mackenzie ( Site 0314)

Curitiba, Paraná, Brazil

Clínica de Neoplasias Litoral ( Site 0305)

Itajaí, Santa Catarina, Brazil

Hospital Universitário São Francisco de Assis - Bragança Paulista ( Site 0308)

Bragança Paulista, São Paulo, Brazil

A. C. Camargo Cancer Center ( Site 0310)

São Paulo, São Paulo, Brazil

Cross Cancer Institute ( Site 0332)

Edmonton, Alberta, Canada

The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 0336)

Ottawa, Ontario, Canada

Sunnybrook Research Institute ( Site 0331)

Toronto, Ontario, Canada

Princess Margaret Cancer Centre ( Site 0330)

Toronto, Ontario, Canada

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 0328)

Greenfield Park, Quebec, Canada

Centre Hospitalier de l'Université de Montréal ( Site 0326)

Montreal, Quebec, Canada

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0327)

Québec, Quebec, Canada

Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer ( Site 0329)

Sherbrooke, Quebec, Canada

IC La Serena Research ( Site 0356)

La Serena, Coquimbo Region, Chile

Clinical Research Chile SpA ( Site 0358)

Valdivia, Los Ríos Region, Chile

Clinica Universidad Catolica del Maule-Oncology ( Site 0355)

Talca, Maule Region, Chile

Fundación Arturo López Pérez ( Site 0353)

Santiago, Region M. de Santiago, Chile

Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 0354)

Santiago, Region M. de Santiago, Chile

Bradfordhill-Clinical Area ( Site 0351)

Santiago, Region M. de Santiago, Chile

Bradford Hill Norte ( Site 0357)

Antofagasta, Chile

Second Affiliated hospital of Anhui Medical University-Urology ( Site 0408)

Hefei, Anhui, China

Peking University First Hospital-Urology ( Site 0390)

Beijing, Beijing Municipality, China

Beijing Friendship Hospital Affiliate of Capital University ( Site 0396)

Beijing, Beijing Municipality, China

Beijing Cancer hospital-Urinary Surgery ( Site 0395)

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Chongqing Medical University ( Site 0427)

Chongqing, Chongqing Municipality, China

Chongqing University Cancer Hospital ( Site 0416)

Chongqing, Chongqing Municipality, China

Southwest Hospital of Third Military Medical University ( Site 0420)

Chongqing, Chongqing Municipality, China

Chongqing Three Gorges Central Hospital's ( Site 0426)

Chongqing, Chongqing Municipality, China

The First Affiliated Hospital Of Fujian Medical University-Urology ( Site 0414)

Fuzhou, Fujian, China

The First Affiliated hospital of Xiamen University-Urology ( Site 0415)

Xiamen, Fujian, China

The First Affiliated Hospital of Guangzhou Medical University ( Site 0412)

Guangzhou, Guangdong, China

Sun Yat-sen University Cancer Center-Internal medicine ( Site 0413)

Guangzhou, Guangdong, China

Tongji Hospital Tongji Medical,Science & Technology ( Site 0407)

Wuhan, Hubei, China

Hubei Cancer Hospital-Urinary surgery ( Site 0406)

Wuhan, Hubei, China

And 188 more locations on ClinicalTrials.gov

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (288)