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)

Merck Sharp & Dohme (MSD)

Status and phase: Begins enrollment this month; Phase 2; Phase 1

Conditions: Metastasis; Castration-Resistant Prostatic Cancer

Treatments: Drug: MK-5684; Drug: Abiraterone; Drug: Docetaxel; Drug: Enzalutamide; Drug: Ifinatamab Deruxtecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT06863272

2400-01A

U1111-1310-5406 (Other Identifier)

IDeate-Prostate02 (Other Identifier)

2024-516036-94 (Registry Identifier)

MK-2400-01A (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

The master screening protocol is MK-2400-U01.

Enrollment: 360 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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360 participants in 4 patient groups

Docetaxel

Active Comparator group

Description:

Participants will receive docetaxel at a determined dose every 3 weeks (Q3W) for a maximum of 10 cycles. Each cycle is 21 days.

Treatment:

Drug: Docetaxel

Ifinatamab Deruxtecan (I-DXd)

Experimental group

Description:

Participants will receive I-DXd at a determined dose Q3W until unacceptable toxicity, progressive disease (PD), death or withdrawal of consent.

Treatment:

Drug: Ifinatamab Deruxtecan

I-DXd + MK-5684

Experimental group

Description:

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.

Treatment:

Drug: Ifinatamab Deruxtecan

Drug: MK-5684

I-DXd +ARPI (Abiraterone or Enzalutamide)

Experimental group

Description:

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.

Treatment:

Drug: Enzalutamide

Drug: Ifinatamab Deruxtecan

Drug: Abiraterone