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)

Official title

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)

Overview

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.

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

Interventions

• Drug Docetaxel
  Administered via Intravenous (IV) infusion at a specified dose on specified days
• Drug Ifinatamab Deruxtecan
  Administered via IV infusion at a specified dose on specified days
• Drug Opevesostat
  Administered orally at a specified dose on specified days
• 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.

Primary outcome measures

• Efficacy Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) - Combination Arms Only [Time frame: Up to approximately 21 days]
• Efficacy Phase: Number of Participants Who Experienced an Adverse Event (AE) [Time frame: Up to approximately 54 months]
• Efficacy Phase: Number of Participants Who Discontinued Study Intervention Due to an AE [Time frame: Up to approximately 24 months]
• Efficacy Phase: Prostate-Specific Antigen (PSA) response rate [Time frame: Up to approximately 54 months]
• Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs) - Combination Arms Only [Time frame: Up to approximately 21 days]
• Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE) - Combination Arms Only [Time frame: Up to approximately 21 days]
• Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE - Combination Arms Only [Time frame: Up to approximately 21 days]

Secondary outcome measures (7)

• Objective Response Rate (ORR) [Time frame: Up to approximately 54 months]
• Radiographic Progression-Free Survival (rPFS) [Time frame: Up to approximately 54 months]
• Overall Survival (OS) [Time frame: Up to approximately 54 months]
• Duration of Response (DOR) [Time frame: Up to approximately 54 months]
• Time from allocation/randomization to initiation of the first subsequent anticancer therapy (TFST) [Time frame: Up to approximately 54 months]
• Time to Prostate-Specific Antigen (PSA) Progression [Time frame: Up to approximately 54 months]
• Time to pain progression (TTPP) [Time frame: Up to approximately 54 months]

Eligibility criteria

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 distant 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:

• Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), current ILD, clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 9 centers

• UCLA Hematology & Oncology ( Site 0003) — Los Angeles
• University of California-Irvine Medical Center ( Site 0016) — Orange
• UCSF Medical Center at Mission Bay ( Site 0034) — San Francisco
• MedStar Georgetown Cancer Institute at MedStar Washington Hospital Center ( Site 0026) — Washington D.C.
• University of Michigan ( Site 0021) — Ann Arbor
• Memorial Sloan Kettering Cancer Center ( Site 0006) — New York
• UPMC Hillman Cancer Center ( Site 0014) — Pittsburgh
• The West Clinic, PLLC dba West Cancer Center ( Site 0005) — Germantown
• … and 1 more center

Brazil · 9 centers

• Liga Norte Riograndense Contra o Câncer ( Site 0271) — Natal
• Irmandade da Santa Casa de Misericórdia de Porto Alegre ( Site 0270) — Porto Alegre
• Hospital Moinhos de Vento ( Site 0278) — Porto Alegre
• Hospital Universitário São Francisco de Assis - Bragança Paulista ( Site 0268) — Bragança Paulista
• Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Pa — Ribeirão Preto
• Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0263) — São José do Rio Preto
• Hospital Alemao Oswaldo Cruz ( Site 0279) — São Paulo
• IPITEC ( Site 0275) — São Paulo
• … and 1 more center

Turkey (Türkiye) · 7 centers

• Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0650) — Adana
• Hacettepe Universitesi Tip Fakultesi ( Site 0648) — Ankara
• Ankara Universitesi Tip Fakultesi Hastanesi ( Site 0653) — Ankara
• Ankara Bilkent Şehir Hastanesi ( Site 0654) — Ankara
• Koç Üniversitesi Hastanesi ( Site 0656) — Istanbul
• Istanbul Universitesi Cerrahpasa ( Site 0649) — Istanbul
• Recep Tayyip Erdogan University Training and Research Hospital ( Site 0655) — Rize

Chile · 5 centers

• Clinica Universidad Catolica del Maule ( Site 0236) — Talca
• FALP ( Site 0232) — Santiago
• Centro de Oncología de Precisión ( Site 0241) — Santiago
• Bradfordhill ( Site 0231) — Santiago
• ONCOCENTRO APYS ( Site 0234) — Viña del Mar

France · 5 centers

• Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest ( S — Bordeaux
• Centre Oscar Lambret ( Site 0495) — Lille
• Institut De Cancerologie De L Ouest ( Site 0494) — Saint-Herblain
• Centre Hospitalier de la Cote Basque ( Site 0496) — Bayonne
• centre hospitalier lyon sud ( Site 0497) — Pierre-Bénite

Israel · 5 centers

• Rambam Health Care Campus ( Site 0400) — Haifa
• Hadassah Medical Center ( Site 0404) — Jerusalem
• Rabin Medical Center ( Site 0402) — Petah Tikva
• Sheba Medical Center ( Site 0401) — Ramat Gan
• Sourasky Medical Center ( Site 0403) — Tel Aviv

Italy · 5 centers

• AOU San Luigi Gonzaga di Orbassano ( Site 0434) — Orbassano
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 0432) — Brescia
• Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0431) — Milan
• A.O.U. Federico II di Napoli ( Site 0435) — Naples
• Fondazione Policlinico Universitario Agostino Gemelli ( Site 0433) — Roma

Spain · 5 centers

• ICO L Hospitalet ( Site 0617) — L Hospitalet Del Llobregat
• Hospital Universitario Ramon y Cajal ( Site 0620) — Madrid
• Hospital Clinico San Carlos ( Site 0618) — Madrid
• Hospital Universitario 12 de Octubre ( Site 0622) — Madrid
• Hospital Universitario Virgen del Rocio ( Site 0619) — Seville

Canada · 4 centers

• BC Cancer - Vancouver Center ( Site 0103) — Vancouver
• Sunnybrook Research Institute ( Site 0109) — Toronto
• Princess Margaret Cancer Centre ( Site 0102) — Toronto
• CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0107) — Sherbrooke

Germany · 4 centers

• NCT ( Site 0528) — Heidelberg
• Universitaetsklinikum Ulm. ( Site 0530) — Ulm
• Universitaetsklinikum Jena ( Site 0525) — Jena
• Universitaetsklinikum Hamburg-Eppendorf ( Site 0524) — Hamburg

Poland · 4 centers

• Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 0590) — Poznan
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w W — Warsaw
• Uniwersyteckie Centrum Kliniczne ( Site 0588) — Gdansk
• Szpital Wojewódzki im. M.Kopernika Oddział Onk. Klinicznej z Pododdziałem Chemioterapii Je — Koszalin

United Kingdom · 4 centers

• Addenbrooke's Hospital ( Site 0747) — Cambridge
• St Bartholomew's Hospital ( Site 0749) — London
• Royal Free Hospital ( Site 0743) — London
• … and 1 more center

Ireland · 3 centers

• St Vincent's University Hospital ( Site 0463) — Dublin
• Beaumont Hospital, Dublin ( Site 0465) — Dublin
• Tallaght University Hospital ( Site 0462) — Dublin

Netherlands · 3 centers

• Ziekenhuis Gelderse Vallei ( Site 0683) — Ede
• UMC St. Radboud ( Site 0679) — Nijmegen
• Nij Smellinghe ( Site 0684) — Drachten

South Korea · 3 centers

• Asan Medical Center ( Site 0925) — Songpagu
• Severance Hospital Yonsei University Health System ( Site 0924) — Seoul
• Samsung Medical Center ( Site 0926) — Seoul

Argentina · 2 centers

• Instituto Alexander Fleming ( Site 0202) — Ciudad Autónoma de Buenos Aires
• Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0200) — La Rioja

Taiwan · 2 centers

• Taichung Veterans General Hospital ( Site 0902) — Taichung
• Taipei Veterans General Hospital ( Site 0901) — Taipei

Australia · 1 center

• Macquarie University-MQ Health Clinical Trials Unit ( Site 0801) — Macquarie University

New Zealand · 1 center

• Auckland City Hospital ( Site 0831) — Auckland

Identifiers

NCT: NCT06863272 · 2400-01A · MK-2400-01A · 2024-516036-94-00 · U1111-1310-5406 · IDeate-Prostate02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗