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)

Phase 2RecruitingNCT06863272

Merck Sharp & Dohme LLC360 enrolled

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

360

Conditions

Castration-Resistant Prostatic Cancer Metastasis

Interventions

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

Ifinatamab DeruxtecanDRUG

Administered via IV infusion at a specified dose on specified days

OpevesostatDRUG

Administered orally at a specified dose on specified days

AbirateroneDRUG

Administered orally at a specified dose on specified days

EnzalutamideDRUG

Administered orally at a specified dose on specified days

Rescue MedicationDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (82)

UCLA Hematology & Oncology ( Site 0003)

Los Angeles, California, United States

RECRUITING

University of California-Irvine Medical Center ( Site 0016)

Orange, California, United States

RECRUITING

UCSF Medical Center at Mission Bay ( Site 0034)

San Francisco, California, United States

RECRUITING

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

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

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.

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 Outcomes

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 PCWG3-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.

Time frame: 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 PCWG3-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG3-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. PCWG3-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 PCWG3 rules include new bone lesions. The rPFS per PCWG3-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

Time frame: 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.

Time frame: 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 PCWG3-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.

Central Contacts

Toll Free Number

CONTACT

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of Michigan ( Site 0021)

Ann Arbor, Michigan, United States

RECRUITING

Memorial Sloan Kettering Cancer Center ( Site 0006)

New York, New York, United States

RECRUITING

UPMC Hillman Cancer Center ( Site 0014)

Pittsburgh, Pennsylvania, United States

RECRUITING

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

Germantown, Tennessee, United States

RECRUITING

Fred Hutchinson Cancer Center ( Site 0013)

Seattle, Washington, United States

RECRUITING

Instituto Alexander Fleming ( Site 0202)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

RECRUITING

...and 72 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 54 months