Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A)

NCT06353386 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: 5684-01AMK-5684-01A2023-506288-33-00U1111-1292-6912jRCT2031240224
• Study Type: interventional
• Target: 220
• Locations: 20 countries
• Sites: 77

Brief Summary

Substudy 01A is part of a larger research study that is testing experimental treatments for metastatic castration-resistant prostate cancer (mCRPC). The larger study is the umbrella study (U01). The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for the opevesostat-based treatment combinations. There will be no hypothesis testing in this study.

Conditions

Prostatic Neoplasms, Castration-Resistant

Outcome Measures

Primary Outcomes (4)

• Number of participants who experience one or more dose-limiting toxicities (DLTs)

  The following events, if considered drug related by the investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not laboratory value); Grade 4 hematologic toxicity lasting \>7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia associated with clinically significant bleeding); Any nonhematologic adverse event (AE) \>Grade 3 in severity should be considered a DLT (with exceptions); Any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); Febrile neutropenia Grade 3 or Grade 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 28 days due to study intervention-related toxicity; Missing \>25% of study intervention doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity.

  Up to approximately 28 days

• Number of participants who experience one or more adverse events (AEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to approximately 46 months

• Number of participants who discontinue study intervention due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to approximately 46 months

• Prostate-specific antigen (PSA) response rate

  The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level will be confirmed by an additional PSA evaluation performed ≥3 weeks from the original response per Prostate Cancer Working Group (PCWG) criteria.

  Up to approximately 46 months

Secondary Outcomes (6)

• Objective response rate (ORR)

  Up to approximately 46 months

• Radiographic progression-free survival (rPFS)

  Up to approximately 46 months

• Overall survival (OS)

  Up to approximately 46 months

• Duration of response (DOR)

  Up to approximately 46 months

• Time to first subsequent anticancer therapy (TFST)

  Up to approximately 46 months

Study Arms (4)

Arm A1: Opevesostat

EXPERIMENTAL

Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation.

Drug: Opevesostat; Drug: Fludrocortisone acetate; Drug: Dexamethasone

Arm A2: Olaparib + Opevesostat

EXPERIMENTAL

Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.

Drug: Opevesostat; Drug: Olaparib; Drug: Fludrocortisone acetate; Drug: Dexamethasone

Arm A3: Docetaxel + Opevesostat

EXPERIMENTAL

Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m\^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.

Drug: Opevesostat; Drug: Docetaxel; Drug: Fludrocortisone acetate; Drug: Dexamethasone; Drug: Prednisone

Arm A4: Cabazitaxel + Opevesostat

EXPERIMENTAL

Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m\^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.

Drug: Opevesostat; Drug: Cabazitaxel; Drug: Fludrocortisone acetate; Drug: Dexamethasone; Drug: Prednisone

Interventions

Olaparib DRUG

Oral Tablet

Also known as: LYNPARZA®

Arm A2: Olaparib + Opevesostat

Docetaxel DRUG

IV Infusion

Also known as: TAXOTERE®

Arm A3: Docetaxel + Opevesostat

Cabazitaxel DRUG

IV Infusion

Also known as: JEVTANA®

Arm A4: Cabazitaxel + Opevesostat

Fludrocortisone acetate DRUG

Oral Tablet

Arm A1: Opevesostat; Arm A2: Olaparib + Opevesostat; Arm A3: Docetaxel + Opevesostat; Arm A4: Cabazitaxel + Opevesostat

Dexamethasone DRUG

Oral Tablet

Arm A1: Opevesostat; Arm A2: Olaparib + Opevesostat; Arm A3: Docetaxel + Opevesostat; Arm A4: Cabazitaxel + Opevesostat

Prednisone DRUG

Oral Tablet

Arm A3: Docetaxel + Opevesostat; Arm A4: Cabazitaxel + Opevesostat

Opevesostat DRUG

Oral Tablet

Also known as: MK-5684

Arm A1: Opevesostat; Arm A2: Olaparib + Opevesostat; Arm A3: Docetaxel + Opevesostat; Arm A4: Cabazitaxel + Opevesostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology.
• Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening.
• Evidence of disease progression from either, \>4 weeks from last flutamide treatment, or \>6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy.
• Current evidence of metastatic disease.
• Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment.
• Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for \>4 weeks before randomization.
• Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to \<Grade 1 or baseline.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
• 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.
• Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

You may not qualify if:

• History of pituitary dysfunction.
• Poorly controlled diabetes mellitus.
• Active or unstable cardio/cerebro-vascular disease, including thromboembolic events and history of stroke or transient ischemic attack within 6 months before the first dose of study intervention, history of myocardial infarction within 6 months before the first dose of study intervention, New York Heart Association Class III or IV cardiac disease or congestive heart failure, coronary heart disease that is symptomatic, or unstable angina
• History or family history of long corrected QT interval (QTc) syndrome.
• Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML.
• History or current condition of adrenal insufficiency.
• History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications.
• Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention.
• Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization).
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• 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 does of study intervention. Administration of killed vaccines is allowed.
• Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (77)

UCSD Moores Cancer Center ( Site 0039)

La Jolla, California, 92037, United States

RECRUITING

UCLA Hematology/Oncology - Santa Monica ( Site 0044)

Los Angeles, California, 90404, United States

RECRUITING

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

Miami, Florida, 33136, United States

RECRUITING

University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049)

Baltimore, Maryland, 21201, United States

ACTIVE NOT RECRUITING

Rutgers Cancer Institute of New Jersey ( Site 0033)

New Brunswick, New Jersey, 08903-2681, United States

RECRUITING

University Hospitals Cleveland Medical Center ( Site 0043)

Cleveland, Ohio, 44106, United States

RECRUITING

MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Macquarie University-MQ Health Clinical Trials Unit ( Site 0108)

Macquarie University, New South Wales, 2109, Australia

RECRUITING

Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107)

Greenslopes, Queensland, 4120, Australia

RECRUITING

Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110)

Melbourne, Victoria, 3000, Australia

RECRUITING

Centre Hospitalier de l'Université de Montréal ( Site 0200)

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Jewish General Hospital ( Site 0206)

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0207)

Québec, Quebec, G1J 1Z4, Canada

RECRUITING

CIDO SpA-Oncology ( Site 0302)

Temuco, Biobio, 4810218, Chile

ACTIVE NOT RECRUITING

Clinica Universidad Catolica del Maule-Oncology ( Site 0304)

Talca, Maule Region, 3465584, Chile

RECRUITING

FALP ( Site 0301)

Santiago, Region M. de Santiago, 7500921, Chile

ACTIVE NOT RECRUITING

Pontificia Universidad Catolica de Chile ( Site 0303)

Santiago, Region M. de Santiago, 832000, Chile

RECRUITING

Bradfordhill ( Site 0300)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0406)

Bogotá, Bogota D.C., 110131, Colombia

RECRUITING

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0402)

Bogotá, Bogota D.C., 111321, Colombia

RECRUITING

Sociedad De Oncología y Hematología Del Cesar SAS-Oncology ( Site 0400)

Valledupar, Cesar Department, 200001, Colombia

RECRUITING

IMAT S.A.S ( Site 0404)

Montería, Departamento de Córdoba, 230002, Colombia

RECRUITING

Fundación Valle del Lili-Oncology CIC ( Site 0403)

Cali, Valle del Cauca Department, 760032, Colombia

RECRUITING

Herlev and Gentofte Hospital ( Site 0501)

Copenhagen, Capital Region, 2730, Denmark

RECRUITING

Aalborg Universitetshospital, Syd ( Site 0503)

Aalborg, North Denmark, 9000, Denmark

RECRUITING

Vaasan Keskussairaala ( Site 0603)

Vaasa, Pohjanmaa, 65130, Finland

RECRUITING

Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus) ( Site 0604)

Helsinki, Uusimaa, 00029, Finland

RECRUITING

Docrates Syöpäsairaala ( Site 0602)

Helsinki, Uusimaa, 00180, Finland

RECRUITING

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0703)

Bordeaux, Aquitaine, 33076, France

RECRUITING

Hopitaux Universitaires de Strasbourg ( Site 0700)

Strasbourg, Bas-Rhin, 67200, France

RECRUITING

Hôpital Européen Georges Pompidou-Service d'Oncologie Médicale ( Site 0702)

Paris, 75015, France

RECRUITING

Gustave Roussy ( Site 0701)

Villejuif, Île-de-France Region, 94805, France

RECRUITING

Universitaetsklinikum Heidelberg ( Site 0805)

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Universitaetsklinikum Tuebingen-Urologie ( Site 0801)

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0802)

Munich, Bavaria, 81675, Germany

RECRUITING

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0800)

Berlin, 10117, Germany

ACTIVE NOT RECRUITING

Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0804)

Hamburg, 20246, Germany

RECRUITING

St. Vincent's University Hospital ( Site 0901)

Dublin, Dublin, D04 T6F4, Ireland

RECRUITING

Cork University Hospital ( Site 0902)

Cork, T12 DC4A, Ireland

RECRUITING

Tallaght University Hospital ( Site 0900)

Dublin, D24 NR0A, Ireland

RECRUITING

Rambam Health Care Campus-Oncology Division ( Site 1002)

Haifa, 3109601, Israel

RECRUITING

Rabin Medical Center ( Site 1001)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 1000)

Ramat Gan, 5265601, Israel

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1102)

Rome, Lazio, 00168, Italy

COMPLETED

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1103)

Milan, Lombardy, 20133, Italy

RECRUITING

Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1101)

Rozzano, Milano, 20089, Italy

RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona - Ospedal-Centro Ricerche Cliniche di Verona ( Site 1100)

Verona, 37134, Italy

RECRUITING

Toho University Sakura Medical Center ( Site 1201)

Sakura, Chiba, 285-8741, Japan

RECRUITING

Yokohama City University Medical Center ( Site 1203)

Yokohama, Kanagawa, 232-0024, Japan

RECRUITING

The Jikei University Hospital ( Site 1202)

Mitato, Tokyo, 105-8471, Japan

COMPLETED

Kyushu University Hospital ( Site 1204)

Fukuoka, 812-8582, Japan

RECRUITING

Auckland City Hospital ( Site 1333)

Auckland, 1023, New Zealand

RECRUITING

Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 1402)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 1400)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne ( Site 1405)

Gdansk, Pomeranian Voivodeship, 80-952, Poland

RECRUITING

Asan Medical Center-Oncology ( Site 1500)

Songpagu, Seoul, 05505, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1502)

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center-Division of Hematology/Oncology ( Site 1501)

Seoul, 06351, South Korea

RECRUITING

Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 1603)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1600)

Madrid, Madrid, Comunidad de, 28034, Spain

RECRUITING

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1602)

Barcelona, 08035, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón ( Site 1601)

Madrid, 28007, Spain

RECRUITING

Hospital Clinico San Carlos-Oncology Department ( Site 1604)

Madrid, 28040, Spain

RECRUITING

Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 1704)

Kaohsiung Niao Sung Dist, Kaohsiung, 83301, Taiwan

RECRUITING

China Medical University Hospital ( Site 1703)

Taichung, 404332, Taiwan

RECRUITING

Taipei Veterans General Hospital ( Site 1701)

Taipei, 112, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou Branch-Medical Oncology ( Site 1702)

Taoyuan District, 333, Taiwan

RECRUITING

Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 1802)

Adana, 01250, Turkey (Türkiye)

RECRUITING

Hacettepe Universite Hastaneleri-oncology hospital ( Site 1800)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Şehir Hastanesi ( Site 1801)

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1804)

Istanbul, 34668, Turkey (Türkiye)

RECRUITING

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1803)

Istanbul, 34722, Turkey (Türkiye)

RECRUITING

Addenbrooke's Hospital ( Site 1902)

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

RECRUITING

The Beatson West of Scotland Cancer Centre ( Site 1904)

Glasgow, Glasgow City, G12 0YN, United Kingdom

RECRUITING

Royal Preston Hospital-Lancashire Clinical Research Facility ( Site 1900)

Preston, Lancashire, PR2 9HT, United Kingdom

RECRUITING

University College London Hospital ( Site 1905)

London, London, City of, NW1 2PG, United Kingdom

RECRUITING

Queen Elizabeth Hospital Birmingham ( Site 1903)

Birmingham, B15 2TH, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

olaparib; Docetaxel; cabazitaxel; fludrocortisone acetate; Dexamethasone; Prednisone

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienediols

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: April 9, 2024
• Study Start: May 20, 2024
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): January 15, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IL (3); DK (2); FI (3); FR (4); TU (5); US (7); CA (3); IE (3); NZ (1); DE (5); GB (5); PL (3); KR (3); AU (3); CO (5); ES (5); CL (5); IT (4); TW (4); JP (4)