Recruiting
Phase 1
Phase 2

Ifinatamab Deruxtecan

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06863272

Conditions

Castration-Resistant Prostatic Cancer

Metastasis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Docetaxel

Ifinatamab Deruxtecan

Opevesostat

Abiraterone

Enzalutamide

Study Details

Brief summary:

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.

Conditions

Castration-Resistant Prostatic Cancer

Metastasis

Study ID

NCT06863272

Start date

Jul 3, 2025

Status verified date

Aug, 2026

Completion date

Apr 1, 2031

Anticipated

Primary completion date

Apr 1, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

360 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

experimental: I-DXd + Opevesostat

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 opevesostat at a determined dose until any of the criterion for discontinuation of study intervention is met.

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.

Interventions

Docetaxel

Administered via Intravenous (IV) infusion at a specified dose on specified days

Ifinatamab Deruxtecan

Administered via IV infusion at a specified dose on specified days

Opevesostat

Administered orally at a specified dose on specified days

Abiraterone

Administered orally at a specified dose on specified days

Enzalutamide

Administered orally at a specified dose on specified days

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 measure

  • 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 ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

UCLA Hematology & Oncology ( Site 0003)

Recruiting

Los Angeles, California, United States, 90095

Contacts

Study Coordinator

310-829-5471

University of California-Irvine Medical Center ( Site 0016)

Recruiting

Orange, California, United States, 92868

Contacts

Study Coordinator

714-456-5153

UCSF Medical Center at Mission Bay ( Site 0034)

Recruiting

San Francisco, California, United States, 94158

Contacts

Study Coordinator

415-502-2097

MedStar Georgetown Cancer Institute at MedStar Washington Hospital Center ( Site 0026)

Recruiting

Washington D.C., District of Columbia, United States, 20010

Contacts

Study Coordinator

202-877-3061

University of Michigan ( Site 0021)

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Study Coordinator

734-936-4000

Memorial Sloan Kettering Cancer Center ( Site 0006)

Recruiting

New York, New York, United States, 10065

Contacts

Study Coordinator

347-798-8620

UPMC Hillman Cancer Center ( Site 0014)

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Study Coordinator

412-647-2811

The West Clinic, PLLC dba West Cancer Center ( Site 0005)

Recruiting

Germantown, Tennessee, United States, 38138

Contacts

Study Coordinator

901-683-0055

Fred Hutchinson Cancer Center ( Site 0013)

Recruiting

Seattle, Washington, United States, 98109

Contacts

Study Coordinator

206-288-1111

BC Cancer - Vancouver Center ( Site 0103)

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Contacts

Study Coordinator

6048776000

Sunnybrook Research Institute ( Site 0109)

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Study Coordinator

4164806100

Princess Margaret Cancer Centre ( Site 0102)

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Study Coordinator

4169464501

Jewish General Hospital ( Site 0108)

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contacts

Study Coordinator

5143408110

CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0107)

Recruiting

Sherbrooke, Quebec, Canada, J1H 5N4

Contacts

Study Coordinator

8197802222

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-21.