A Study of JNJ-87189401 Combined With JNJ-78278343 for Advanced Prostate Cancer

A Phase 1 Study of JNJ-87189401 (PSMA-CD28 Bispecific Antibody) Combined With JNJ-78278343 (KLK2-CD3 Bispecific Antibody) for Advanced Prostate Cancer

The purpose of Parts 1, 2A, and 2B of the study is to determine the recommended regimen for Phase 2 (RP2Rs) of combination of JNJ-87189401 with JNJ-78278343 and the purpose of Part 2C of this study is to determine how safe the RP2R(s) of the combination of JNJ-87189401 and JNJ-78278343 is, with or without apalutamide. Part 3 of this study evaluates the safety of the triplet combination of JNJ-87189401 and JNJ-78278343 with standard of care (SOC) lutetium Lu-177 vipivotide tetraxetan. Part 4 of this study further evaluates the safety of the triplet combination of JNJ-87189401 and JNJ-78278343 with JNJ-101556143 in participants with advanced prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: JNJ-78278343; Drug: JNJ-87189401; Drug: Apalutamide; Drug: Lutetium Lu-177 Vipivotide Tetraxetan; Drug: JNJ-101556143

• Study Type: Interventional
• Enrollment (Estimated): 355
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• France
  • Bordeaux, France, 33000
    • Recruiting
    • Institut Bergonié
  • Lyon, France, 69008
    • Recruiting
    • Centre Léon Berard
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
• Japan
  • Tokyo, Japan, 135 8550
    • Recruiting
    • The Cancer Institute Hospital of JFCR
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • START New Jersey
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Herbert Irving Comprehensive Cancer Center Columbia University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Sidney Kimmel Cancer Center - Jefferson Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics, LLC (START)
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted. However, small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed
• Measurable or evaluable disease per PCWG3 criteria
• Part 1, Parts 2A, 2B, 3 and 4: Prior orchiectomy or medical castration; participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), prior to the first dose of study drug and must continue this therapy throughout the treatment phase
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• History of an autoimmune disease within the 12 months prior to signing consent
• Any of the following within 6 months prior to signature of informed consent: a. myocardial infarction, b. severe or unstable angina, c. clinically significant ventricular arrhythmias, d. congestive heart failure (New York Heart Association [NYHA] class II to IV), e. transient ischemic attack, and f. Cerebrovascular accident

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (Dose Escalation); Participants will receive JNJ-78278343 + JNJ-87189401 escalated sequentially in Part 1 to select a recommended Phase 2 regimen (RP2R).	Drug: JNJ-78278343; JNJ-78278343 will be administered.; Other Names: KLK2-CD3; Pasritamig; Drug: JNJ-87189401; JNJ-87189401 will be administered.; Other Names: PSMAxCD28
Experimental: Part 2 (Dose Expansion); Participants with different disease settings in Parts 2A and 2B will receive JNJ-78278343+JNJ-87189401 at the RP2R selected in Part 1. Participants in Part 2C will receive apalutamide plus continued treatment with JNJ-87189401+JNJ-78278343 doublet.	Drug: JNJ-78278343; JNJ-78278343 will be administered.; Other Names: KLK2-CD3; Pasritamig; Drug: JNJ-87189401; JNJ-87189401 will be administered.; Other Names: PSMAxCD28; Drug: Apalutamide; Apalutamide will be administered.
Experimental: Part 3; Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) selected in Part 1 along with standard of care (SOC) treatment with lutetium Lu-177 vipivotide tetraxetan. Dosing of JNJ-78278343+JNJ-87189401 will be escalated sequentially, as per study evaluation team (SET) decision.	Drug: JNJ-78278343; JNJ-78278343 will be administered.; Other Names: KLK2-CD3; Pasritamig; Drug: JNJ-87189401; JNJ-87189401 will be administered.; Other Names: PSMAxCD28; Drug: Lutetium Lu-177 Vipivotide Tetraxetan; Lutetium Lu-177 Vipivotide Tetraxetan will be administered as SOC treatment.
Experimental: Part 4; Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) along with JNJ-101556143. Dosing of JNJ-78278343+JNJ-87189401 along with JNJ-101556143 will be escalated sequentially to determine the RP2R of the combinations.	Drug: JNJ-78278343; JNJ-78278343 will be administered.; Other Names: KLK2-CD3; Pasritamig; Drug: JNJ-87189401; JNJ-87189401 will be administered.; Other Names: PSMAxCD28; Drug: JNJ-101556143; JNJ-101556143 will be administered.; Other Names: HLD-0915

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1, 2C, 3 and 4: Number of Participants With Dose Limiting Toxicity (DLT)	DLTs are specific adverse events (AEs) and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity.	Up to 21 days after first combination dose of study drugs
Number of Participants with Adverse Events (AEs) by Severity	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome events, which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event.	Up to 4 years 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentrations of JNJ-87189401 and JNJ-78278343	Serum samples will be analyzed to determine concentrations of JNJ-87189401 and JNJ-78278343.	Up to 4 years 8 months
Plasma Concentration of JNJ-101556143	Plasma samples will be analyzed to determine concentrations of JNJ-101556143.	Up to 4 years 8 months
Number of Participants With Antibodies to JNJ-87189401 and JNJ-78278343	Number of participants with antibodies to JNJ-87189401 and JNJ-78278343 will be reported.	Up to 4 years 8 months
Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a partial response (PR) or better according to response evaluation criteria in solid tumors (RECIST) version 1.1 without evidence of bone progression according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3).	Up to 4 years 8 months
Radiographic Progression-Free Survival (rPFS)	rPFS is defined time from the date of first dose of study drug until the date of objective disease progression or death, whichever comes first.	Up to 4 years 8 months
Prostate Specific Antigen (PSA) Response Rate	PSA response rate is defined as the percentage of participants with a confirmed decline of PSA of 50 percent (%) or more from baseline.	Up to 4 years 8 months
Duration of Response (DOR)	DOR is defined for participants who achieved response (PR or better) as the time between the date of initial documentation of response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3, or death due to any cause, whichever occurs first.	Up to 4 years 8 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): June 21, 2027
• Study Completion (Estimated): June 28, 2028

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; apalutamide
• Other Study ID Numbers: CR109330; 87189401PCR1001 (Other Identifier: Janssen Research & Development, LLC); 2023-504063-17-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes