Clinical trial NCT06353386: 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)
Official title: MK-5684-01A Substudy: A Phase 1/2 Umbrella Substudy of MK-5684-U01 Master Protocol to Evaluate the Safety and Efficacy of MK-5684-based Treatment Combinations or MK-5684 Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms, Castration-Resistant
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2024-04-09
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* 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.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* 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.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Active autoimmune disease that has required systemic treatment in the past 2 years.
* Active infection requiring systemic therapy.
* Concurrent active HBV or HCV infections.

Primary outcomes:
measure: Number of participants who experience one or more dose-limiting toxicities (DLTs)
timeFrame: Up to approximately 28 days
measure: Number of participants who experience one or more adverse events (AEs)
timeFrame: Up to approximately 46 months
measure: Number of participants who discontinue study intervention due to an AE
timeFrame: Up to approximately 46 months
measure: Prostate-specific antigen (PSA) response rate
timeFrame: Up to approximately 46 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to approximately 46 months
measure: Radiographic progression-free survival (rPFS)
timeFrame: Up to approximately 46 months
measure: Overall survival (OS)
timeFrame: Up to approximately 46 months
measure: Duration of response (DOR)
timeFrame: Up to approximately 46 months
measure: Time to first subsequent anticancer therapy (TFST)
timeFrame: Up to approximately 46 months
measure: Time to pain progression (TTPP)
timeFrame: Up to approximately 46 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center ( Site 0039)
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology - Santa Monica ( Site 0044)
state: California
city: Miami
country: United States
facility: University of Miami Hospital and Clinics, Sylvester Cancer Center-Cancer Research Services ( Site 0051)
state: Florida
city: Baltimore
country: United States
facility: University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0049)
state: Maryland
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0033)
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center ( Site 0043)
state: Ohio
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0020)
state: Wisconsin
city: Macquarie University
country: Australia
facility: Macquarie University-MQ Health Clinical Trials Unit ( Site 0108)
state: New South Wales
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107)
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110)
state: Victoria
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0206)
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal ( Site 0200)
state: Quebec
city: Quebec
country: Canada
facility: Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0207)
city: Temuco
country: Chile
facility: CIDO SpA-Oncology ( Site 0302)
state: Biobio
city: Talca
country: Chile
facility: Clinica Universidad Catolica del Maule-Oncology ( Site 0304)
state: Maule
city: Santiago
country: Chile
facility: FALP ( Site 0301)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 0303)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill ( Site 0300)
state: Region M. De Santiago
city: Valledupar
country: Colombia
facility: Sociedad De Oncología y Hematología Del Cesar SAS-Oncology ( Site 0400)
state: Cesar
city: Monteria
country: Colombia
facility: IMAT S.A.S ( Site 0404)
state: Cordoba
city: Bogota
country: Colombia
facility: FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0406)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0402)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundación Valle del Lili-Oncology CIC ( Site 0403)
state: Valle Del Cauca
city: Copenhagen
country: Denmark
facility: Herlev and Gentofte Hospital ( Site 0501)
state: Hovedstaden
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital, Syd ( Site 0503)
state: Nordjylland
city: Vaasa
country: Finland
facility: Vaasan Keskussairaala ( Site 0603)
state: Pohjanmaa
city: Helsinki
country: Finland
facility: Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus) ( Site 0604)
state: Uusimaa
city: Helsinki
country: Finland
facility: Docrates Syöpäsairaala ( Site 0602)
state: Uusimaa
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0700)
state: Alsace
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0703)
state: Aquitaine
city: Villejuif
country: France
facility: Gustave Roussy ( Site 0701)
state: Ile-de-France
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou-Service d'Oncologie Médicale ( Site 0702)
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg ( Site 0805)
state: Baden-Wurttemberg
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen-Urologie ( Site 0801)
state: Baden-Wurttemberg
city: Munich
country: Germany
facility: klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Site 0802)
state: Bayern
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0800)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0804)
city: Dublin 4
country: Ireland
facility: St. Vincent's University Hospital ( Site 0901)
state: Dublin
city: Cork
country: Ireland
facility: Cork University Hospital ( Site 0902)
city: Dublin
country: Ireland
facility: Tallaght University Hospital ( Site 0900)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology Division ( Site 1002)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 1001)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 1000)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1102)
state: Lazio
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1103)
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1101)
state: Milano
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 1100)
state: Veneto
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center ( Site 1201)
state: Chiba
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center ( Site 1203)
state: Kanagawa
city: Mitato
country: Japan
facility: The Jikei University Hospital ( Site 1202)
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital ( Site 1204)
city: Songpagu
country: Korea, Republic of
facility: Asan Medical Center-Oncology ( Site 1500)
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1502)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Division of Hematology/Oncology ( Site 1501)
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 1333)
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 1402)
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 1400)
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne ( Site 1405)
state: Pomorskie
city: L Hospitalet
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 1603)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1600)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1602)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón ( Site 1601)
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos-Oncology Department ( Site 1604)
city: Kaohsiung Niao Sung Dist
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 1704)
state: Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 1703)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 1701)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch-Medical Oncology ( Site 1702)
city: Adana
country: Turkey
facility: Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 1802)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-oncology hospital ( Site 1800)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi ( Site 1801)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1804)
city: Istanbul
country: Turkey
facility: TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1803)
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital ( Site 1902)
state: Cambridgeshire
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre ( Site 1904)
state: Glasgow City
city: Preston
country: United Kingdom
facility: Royal Preston Hospital-Lancashire Clinical Research Facility ( Site 1900)
state: Lancashire
city: London
country: United Kingdom
facility: University College London Hospital ( Site 1905)
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham ( Site 1903)
state: Warwickshire
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: