A Clinical Study of Ifinatamab Deruxtecan Based Treatment Combinations or as Monotherapy to Treat Metastatic Castrate Resistant Prostate Cancer (mCRPC) (MK-2400-01A/IDeate-Prostate02)

MK-2400-01A Substudy: A Phase 1/2, Open-label Umbrella Substudy of MK-2400-U01 Master Protocol to Evaluate the Safety and Efficacy of Ifinatamab Deruxtecan-based Treatment Combinations or Ifinatamab Deruxtecan Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (IDeate-Prostate02)

The purpose of this substudy is to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd), given alone or with other treatments in participants with metastatic castration-resistant prostate cancer (mCRPC). The goals of this study are to learn about:

• The safety of the study treatment and if people tolerate it.
• A safe dose level of I-DXd that can be used with other treatments.
• Participant levels of prostate specific antigen (PSA) during treatment.

Study Overview

• Status: Recruiting
• Conditions: Metastasis; Castration-Resistant Prostatic Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Ifinatamab Deruxtecan; Drug: MK-5684; Drug: Abiraterone; Drug: Enzalutamide; Drug: Rescue Medication

Detailed Description

This sub study MK-2400-01A assesses treatments for metastatic castration-resistant prostate cancer (mCRPC).

The master screening protocol is MK-2400-U01

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Argentina
  • La Rioja, Argentina, F5300COE
    • Recruiting
    • Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0200)
    • Contact: Study Coordinator; Phone Number: 54-380-443-6443
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Recruiting
      • Instituto Alexander Fleming ( Site 0202)
      • Contact: Study Coordinator; Phone Number: 5411 3221 8900
• Australia
  • New South Wales
    • Macquarie University, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University-MQ Health Clinical Trials Unit ( Site 0801)
      • Contact: Study Coordinator; Phone Number: +61 2 9812 2956
• Brazil
  • São Paulo, Brazil, 01221-020
    • Recruiting
    • IPITEC ( Site 0275)
    • Contact: Study Coordinator; Phone Number: +551194322-6006
  • São Paulo, Brazil, 03102-006
    • Recruiting
    • IBCC - Instituto Brasileiro de Controle do Câncer ( Site 0269)
    • Contact: Study Coordinator; Phone Number: +551144500360
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59062-000
      • Recruiting
      • Liga Norte Riograndense Contra o Câncer ( Site 0271)
      • Contact: Study Coordinator; Phone Number: (84) 4009-5595
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-001
      • Recruiting
      • Hospital Moinhos de Vento ( Site 0278)
      • Contact: Study Coordinator; Phone Number: +55 51 3314-3209
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Recruiting
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre ( Site 0270)
      • Contact: Study Coordinator; Phone Number: +555132148151
  • São Paulo
    • Bragança Paulista, São Paulo, Brazil, 12916-542
      • Recruiting
      • Hospital Universitário São Francisco de Assis - Bragança Paulista ( Site 0268)
      • Contact: Study Coordinator; Phone Number: +551124901366
    • Ribeirão Preto, São Paulo, Brazil, 14048900
      • Recruiting
      • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP) ( Site 0273)
      • Contact: Study Coordinator; Phone Number: (16) 3963-6487
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Recruiting
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0263)
      • Contact: Study Coordinator; Phone Number: +55 17 99625-3919
    • São Paulo, São Paulo, Brazil, 01327-001
      • Recruiting
      • Hospital Alemao Oswaldo Cruz ( Site 0279)
      • Contact: Study Coordinator; Phone Number: 55 11 3549-0009
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BC Cancer - Vancouver Center ( Site 0103)
      • Contact: Study Coordinator; Phone Number: 6048776000
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre ( Site 0102)
      • Contact: Study Coordinator; Phone Number: 4169464501
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Research Institute ( Site 0109)
      • Contact: Study Coordinator; Phone Number: 4164806100
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital ( Site 0108)
      • Contact: Study Coordinator; Phone Number: 5143408110
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0107)
      • Contact: Study Coordinator; Phone Number: 8197802222
• Chile
  • Maule Region
    • Talca, Maule Region, Chile, 3465584
      • Recruiting
      • Clinica Universidad Catolica del Maule ( Site 0236)
      • Contact: Study Coordinator; Phone Number: 56992992913
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Recruiting
      • Bradfordhill ( Site 0231)
      • Contact: Study Coordinator; Phone Number: +56229490970
    • Santiago, Region M. de Santiago, Chile, 7500921
      • Recruiting
      • FALP ( Site 0232)
      • Contact: Study Coordinator; Phone Number: 56224205098
    • Santiago, Region M. de Santiago, Chile, 7560908
      • Recruiting
      • Centro de Oncología de Precisión ( Site 0241)
      • Contact: Study Coordinator; Phone Number: +56225189885
  • Valparaiso
    • Viña del Mar, Valparaiso, Chile, 2520598
      • Recruiting
      • ONCOCENTRO APYS ( Site 0234)
      • Contact: Study Coordinator; Phone Number: +56323320850
• France
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Recruiting
      • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( Site 0498)
      • Contact: Study Coordinator; Phone Number: +33556333261
  • Nord
    • Lille, Nord, France, 59000
      • Recruiting
      • Centre Oscar Lambret ( Site 0495)
      • Contact: Study Coordinator; Phone Number: +333 20 29 56 06
  • Pays de la Loire Region
    • Saint-Herblain, Pays de la Loire Region, France, 44800
      • Recruiting
      • Institut De Cancerologie De L Ouest ( Site 0494)
      • Contact: Study Coordinator; Phone Number: +33240679900
  • Pyrenees-Atlantiques
    • Bayonne, Pyrenees-Atlantiques, France, 64100
      • Recruiting
      • Centre Hospitalier de la Côte Basque ( Site 0496)
      • Contact: Study Coordinator; Phone Number: +33559443762
  • Rhone
    • Pierre-Bénite, Rhone, France, 69310
      • Recruiting
      • centre hospitalier lyon sud ( Site 0497)
      • Contact: Study Coordinator; Phone Number: 33 4 78 86 43 24
• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaetsklinikum Hamburg-Eppendorf ( Site 0524)
    • Contact: Study Coordinator; Phone Number: +4915222815585
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Recruiting
      • NCT ( Site 0528)
      • Contact: Study Coordinator; Phone Number: 00496221566857
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Recruiting
      • Universitaetsklinikum Jena ( Site 0525)
      • Contact: Study Coordinator; Phone Number: +49-3641-9-329901
• Ireland
  • Dublin, Ireland, D09 V2N0
    • Recruiting
    • Beaumont Hospital, Dublin ( Site 0465)
    • Contact: Study Coordinator; Phone Number: 0035318092010
  • Dublin, Ireland, D24 NR0A
    • Recruiting
    • Tallaght University Hospital ( Site 0462)
    • Contact: Study Coordinator; Phone Number: 0035314144209
  • Dublin
    • Dublin, Dublin, Ireland, D04 T6F4
      • Recruiting
      • St Vincent's University Hospital ( Site 0463)
      • Contact: Study Coordinator; Phone Number: +353 1 221 4982
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus ( Site 0400)
    • Contact: Study Coordinator; Phone Number: 972(47776234)
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center ( Site 0404)
    • Contact: Study Coordinator; Phone Number: +97226777333
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center ( Site 0402)
    • Contact: Study Coordinator; Phone Number: +972544594048
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center ( Site 0401)
    • Contact: Study Coordinator; Phone Number: +97235303030
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Sourasky Medical Center ( Site 0403)
    • Contact: Study Coordinator; Phone Number: +97236947832
• Italy
  • Brescia, Italy, 25123
    • Recruiting
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 0432)
    • Contact: Study Coordinator; Phone Number: 00390303995410
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0431)
    • Contact: Study Coordinator; Phone Number: +390223904449
  • Naples, Italy, 80131
    • Recruiting
    • A.O.U. Federico II di Napoli ( Site 0435)
    • Contact: Study Coordinator; Phone Number: +390817463660
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli ( Site 0433)
    • Contact: Study Coordinator; Phone Number: +390630155202
  • Torino
    • Orbassano, Torino, Italy, 10143
      • Recruiting
      • AOU San Luigi Gonzaga di Orbassano ( Site 0434)
      • Contact: Study Coordinator; Phone Number: 00390119026534
• Netherlands
  • Gelderland
    • Ede, Gelderland, Netherlands, 6716 RP
      • Recruiting
      • Ziekenhuis Gelderse Vallei ( Site 0683)
      • Contact: Study Coordinator; Phone Number: +31 318 435499
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • UMC St. Radboud ( Site 0679)
      • Contact: Study Coordinator; Phone Number: +31 24 361 1111
  • Provincie Friesland
    • Drachten, Provincie Friesland, Netherlands, 9202 NN
      • Recruiting
      • Nij Smellinghe ( Site 0684)
      • Contact: Study Coordinator; Phone Number: 0512 588 888
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital ( Site 0831)
    • Contact: Study Coordinator; Phone Number: +6493074949
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-355
      • Recruiting
      • Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0590)
      • Contact: Study Coordinator; Phone Number: +61 854 79 87
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Recruiting
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0586)
      • Contact: Study Coordinator; Phone Number: +48 22 546 33 81
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne ( Site 0588)
      • Contact: Study Coordinator; Phone Number: +48 58 584 44 66
  • West Pomeranian Voivodeship
    • Koszalin, West Pomeranian Voivodeship, Poland, 75-581
      • Recruiting
      • Szpital Wojewódzki im. M.Kopernika Oddział Onk. Klinicznej z Pododdziałem Chemioterapii Jednodniowej ( Site 0587)
      • Contact: Study Coordinator; Phone Number: +48943488930
• South Korea
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center ( Site 0926)
    • Contact: Study Coordinator; Phone Number: +82234103459
  • Seoul, South Korea, 03722
    • Active, not recruiting
    • Severance Hospital Yonsei University Health System ( Site 0924)
  • Seoul
    • Songpagu, Seoul, South Korea, 05505
      • Recruiting
      • Asan Medical Center ( Site 0925)
      • Contact: Study Coordinator; Phone Number: +82230105977
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal ( Site 0620)
    • Contact: Study Coordinator; Phone Number: +34913368263
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre ( Site 0622)
    • Contact: Study Coordinator; Phone Number: +34608464547
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos ( Site 0618)
    • Contact: Study Coordinator; Phone Number: +34913303546
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio ( Site 0619)
    • Contact: Study Coordinator; Phone Number: +34955013068
  • Barcelona
    • L Hospitalet Del Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • ICO L Hospitalet ( Site 0617)
      • Contact: Study Coordinator; Phone Number: +34932607744
• Taiwan
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital ( Site 0902)
    • Contact: Study Coordinator; Phone Number: +886423592525
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital ( Site 0901)
    • Contact: Study Coordinator; Phone Number: +886228712121
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Recruiting
    • Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0650)
    • Contact: Study Coordinator; Phone Number: +903223271274
  • Ankara, Turkey (Türkiye), 06230
    • Recruiting
    • Hacettepe Universitesi Tip Fakultesi ( Site 0648)
    • Contact: Study Coordinator; Phone Number: +90 312 305 50 00
  • Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara Bilkent Şehir Hastanesi ( Site 0654)
    • Contact: Study Coordinator; Phone Number: +903125526000
  • Ankara, Turkey (Türkiye), 06620
    • Recruiting
    • Ankara Universitesi Tip Fakultesi Hastanesi ( Site 0653)
    • Contact: Study Coordinator; Phone Number: +903122126040
  • Istanbul, Turkey (Türkiye), 34010
    • Recruiting
    • Koç Üniversitesi Hastanesi ( Site 0656)
    • Contact: Study Coordinator; Phone Number: +905369410661
  • Istanbul, Turkey (Türkiye), 34098
    • Recruiting
    • Istanbul Universitesi Cerrahpasa ( Site 0649)
    • Contact: Study Coordinator; Phone Number: +902124143000
  • Rize, Turkey (Türkiye), 53020
    • Recruiting
    • Recep Tayyip Erdogan University Training and Research Hospital ( Site 0655)
    • Contact: Study Coordinator; Phone Number: +904642130491
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
      • Recruiting
      • Addenbrooke's Hospital ( Site 0747)
      • Contact: Study Coordinator; Phone Number: 00441223216083
  • London, City of
    • London, London, City of, United Kingdom, NW3 2QG
      • Recruiting
      • Royal Free Hospital ( Site 0743)
      • Contact: Study Coordinator; Phone Number: 00442077940500/2237
    • London, London, City of, United Kingdom, EC1A 7BE
      • Recruiting
      • St Bartholomew's Hospital ( Site 0749)
      • Contact: Study Coordinator; Phone Number: 00442073777000
  • Surrey
    • London, Surrey, United Kingdom, SM3 5PT
      • Recruiting
      • Royal Marsden Hospital (Sutton) ( Site 0741)
      • Contact: Study Coordinator; Phone Number: 0203 437 3500
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Hematology & Oncology ( Site 0003)
      • Contact: Study Coordinator; Phone Number: 310-829-5471
    • Orange, California, United States, 92868
      • Recruiting
      • University of California-Irvine Medical Center ( Site 0016)
      • Contact: Study Coordinator; Phone Number: 714-456-5153
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Medical Center at Mission Bay ( Site 0034)
      • Contact: Study Coordinator; Phone Number: 415-502-2097
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • MedStar Georgetown Cancer Institute at MedStar Washington Hospital Center ( Site 0026)
      • Contact: Study Coordinator; Phone Number: 202-877-3061
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center ( Site 0006)
      • Contact: Study Coordinator; Phone Number: 347-798-8620
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center ( Site 0014)
      • Contact: Study Coordinator; Phone Number: 412-647-2811
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • The West Clinic, PLLC dba West Cancer Center ( Site 0005)
      • Contact: Study Coordinator; Phone Number: 901-683-0055
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center ( Site 0013)
      • Contact: Study Coordinator; Phone Number: 206-288-1111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before Screening
• Has current evidence of metastatic disease
• Has received prior treatment with 1 or 2 androgen receptor pathway inhibitors (ARPIs) and progressed during or after treatment
• Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks before allocation/randomization
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 10 days before allocation/randomization
• Has prior treatment with poly-ADP-ribose polymerase inhibitors (PARPi) if indicated by local approved regimen or were deemed ineligible to receive PARPi by the investigator

Exclusion Criteria:

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

• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or has current ILD/pneumonitis or suspected ILD/pneumonitis
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
• Uncontrolled or significant cardiovascular disease
• History of pituitary dysfunction
• Poorly controlled diabetes mellitus
• History or current condition of adrenal insufficiency (eg, Addison's disease)
• Has received prior treatment with taxane-based chemotherapy agent for metastatic castration-resistant prostate cancer (mCRPC).
• Chronic steroid treatment (dose of >10 mg daily prednisone equivalent), except for low-dose inhaled steroids (for asthma/chronic obstructive pulmonary disease), topical steroids (for mild skin conditions), or intra-articular steroid injections
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• 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
• History of allogeneic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Docetaxel; Participants will receive docetaxel at a determined dose every 3 weeks (Q3W) for a maximum of 10 cycles. Each cycle is 21 days.	Drug: Docetaxel; Administered via Intravenous (IV) infusion at a specified dose on specified days
Experimental: Ifinatamab Deruxtecan (I-DXd); Participants will receive I-DXd at a determined dose Q3W until unacceptable toxicity, progressive disease (PD), death or withdrawal of consent.	Drug: Ifinatamab Deruxtecan; Administered via IV infusion at a specified dose on specified days; Other Names: I-DXd, MK-2400, DS-7300a; Drug: Rescue Medication; Before each dose of I-DXd, participants are required to take premedication for prevention of nausea and vomiting with a 2- or 3-drug combination regimen (eg, dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) per approved product label.
Experimental: I-DXd + MK-5684; Following a dose escalation regimen with I-DXd, participants will receive I-DXd at a determined dose until unacceptable toxicity, PD, death or withdrawal of consent PLUS MK-5684 at a determined dose until any of the criterion for discontinuation of study intervention is met.	Drug: Ifinatamab Deruxtecan; Administered via IV infusion at a specified dose on specified days; Other Names: I-DXd, MK-2400, DS-7300a; Drug: MK-5684; Administered orally at a specified dose on specified days; Other Names: ODM-208; Drug: Rescue Medication; Before each dose of I-DXd, participants are required to take premedication for prevention of nausea and vomiting with a 2- or 3-drug combination regimen (eg, dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) per approved product label.
Experimental: I-DXd +ARPI (Abiraterone or Enzalutamide); Following a dose escalation regimen with I-DXd, participants will receive I-DXd at a determined dose until unacceptable toxicity, PD, death or withdrawal of consent PLUS ARPI (Androgen Receptor Pathway Inhibitor) - Abiraterone acetate OR Enzalutamide at a determined dose until any of the criterion for discontinuation of study intervention is met.	Drug: Ifinatamab Deruxtecan; Administered via IV infusion at a specified dose on specified days; Other Names: I-DXd, MK-2400, DS-7300a; Drug: Abiraterone; Administered orally at a specified dose on specified days; Drug: Enzalutamide; Administered orally at a specified dose on specified days; Drug: Rescue Medication; Before each dose of I-DXd, participants are required to take premedication for prevention of nausea and vomiting with a 2- or 3-drug combination regimen (eg, dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) per approved product label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) - Combination Arms Only	The following events if considered drug related by the Investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not based on 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; Nonhematologic AEs ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for >1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 or 4 febrile neutropenia; Study intervention - related toxicities that lead to discontinuation of study treatment during Cycle 1; Prolonged delay (>2 weeks) in initiating Cycles 2 due to treatment-related toxicity; Missing >25% of study intervention doses as a result of treatment-related AE during Cycle 1; Grade 5 toxicity.	Up to approximately 21 days
Efficacy Phase: Number of Participants Who Experienced an Adverse Event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 54 months
Efficacy Phase: Number of Participants Who Discontinued 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 24 months
Efficacy Phase: Prostate-Specific Antigen (PSA) response rate	PSA response is defined per prostate cancer working group (PCWG) criteria as a reduction in the PSA level of 50% or more from baseline measured at consecutive assessments at least 3 weeks apart.	Up to approximately 54 months
Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) - Combination Arms Only	The following events if considered drug related by the Investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not based on 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; Nonhematologic AEs ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for >1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 or 4 febrile neutropenia; Study intervention - related toxicities that lead to discontinuation of study treatment during Cycle 1; Prolonged delay (>2 weeks) in initiating Cycles 2 due to treatment-related toxicity; Missing >25% of study intervention doses as a result of treatment-related AE during Cycle 1; Grade 5 toxicity.	Up to approximately 21 days
Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE) - Combination Arms Only	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 21 days
Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE - Combination Arms Only	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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 54 months
Radiographic Progression-Free Survival (rPFS)	rPFS is defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG-modified RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions or ≥2 new bone lesions was also considered PD. PCWG-modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1 and PCWG rules include new bone lesions. The rPFS per PCWG-modified RECIST as assessed by BICR for all participants is presented. The nonparametric Kaplan-Meier method will be used to estimate the rPFS curve in each treatment arm	Up to approximately 54 months
Overall Survival (OS)	Overall survival (OS) is defined as the time from randomization to death due to any cause. The nonparametric Kaplan-Meier method will be used to estimate the survival curves.	Up to approximately 54 months
Duration of Response (DOR)	DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per PCWG-modified RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥ 2 new bone lesions is also considered PD. DOR as assessed by BICR is presented. The nonparametric Kaplan-Meier method will be used to estimate the DOR in each treatment arm.	Up to approximately 54 months
Time from allocation/randomization to initiation of the first subsequent anticancer therapy (TFST)	TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first. The nonparametric Kaplan-Meier method will be used to estimate the TFST in each treatment arm.	Up to approximately 54 months
Time to Prostate-Specific Antigen (PSA) Progression	Time to PSA progression is defined as the time from randomization to PSA progression. Participants without PSA progression will be censored at the last PSA assessment date. The PSA progression date is defined as the date of: 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, OR 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.	Up to approximately 54 months
Time to pain progression (TTPP)	The time from allocation/randomization to pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 "worst pain in 24 hours" and by the Analgesic Quantification Algorithm (AQA) score.	Up to approximately 54 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Daiichi Sankyo
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2025
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 7, 2025

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Prostatic Neoplasms; Neoplasm Metastasis; Prostatic Neoplasms, Castration-Resistant; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; abiraterone; enzalutamide
• Other Study ID Numbers: 2400-01A; MK-2400-01A (Other Identifier: MSD); U1111-1310-5406 (Registry Identifier: UTN); IDeate-Prostate02 (Other Identifier: MSD); 2024-516036-94-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No