A Study of Pasritamig (JNJ-78278343) in Combination With JNJ-86974680 for Treatment of Prostate Cancer

A Phase 1b Study of Pasritamig (JNJ-78278343), a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2), in Combination With JNJ-86974680, an A2a Receptor (A2aR) Antagonist, for Prostate Cancer

The purpose of this study is to identify the recommended phase 2 combination dose (RP2CD) of Pasritamig in combination with JNJ-86974680 in Part 1 (Dose finding) of the study and to determine how safe and tolerable the RP2CD is for treatment of participants with advanced prostate cancer in Part 2 (Dose expansion) of study.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Pasritamig; Drug: JNJ-86974680

• Study Type: Interventional
• Enrollment (Estimated): 40
• 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

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust Christie Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • Royal Marsden Hospital
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland 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. Primary small cell carcinoma, carcinoid tumor, neuroendocrine (NE) carcinoma, or large cell NE carcinoma arising in the prostate are not allowed; however, adenocarcinomas with NE features (for example [e.g.], immunohistochemistry [IHC] with both androgen receptor [AR]- and NE-marker positivity) are allowed
• Metastatic castration-resistant prostate cancer (mCRPC) that is metastatic either to bone, any lymph node, or both without clear evidence of metastasis to visceral organs. Local-regional invasion (rectum, bladder) and bone disease with soft tissue component can be included
• Prior orchiectomy or medical castration (for example, 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)
• Prostate-specific antigen (PSA) greater than or equal to (>=) 2 nanograms per milliliters (ng/mL) at screening
• Measurable or evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion criteria:

• Toxicity related to prior anticancer therapy that has not returned to grade less than or equal to (<=) 1 or baseline levels (except for alopecia, neuropathy [Grade 2] and vitiligo)
• Known allergies, hypersensitivity, or intolerance to any of the components (for example, excipients) of pasritamig or JNJ-86974680
• Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study treatment. Antibiotic or antiviral prophylaxis is allowed
• Have leptomeningeal disease or brain metastases, except participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic >2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment
• Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Finding; Participants will receive pasritamig in combination with JNJ-86974680 to determine the recommended phase 2 combination dose (RP2CD) regimen.	Drug: Pasritamig; Pasritamig will be administered intravenously.; Other Names: JNJ-78278343; Drug: JNJ-86974680; JNJ-86974680 will be administered orally.
Experimental: Part 2: Dose Expansion; Participants will receive pasritamig in combination with JNJ-86974680 at the RP2CD as determined in Part 1 of the study to confirm the safety and anti-tumor activity.	Drug: Pasritamig; Pasritamig will be administered intravenously.; Other Names: JNJ-78278343; Drug: JNJ-86974680; JNJ-86974680 will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Dose-Limiting Toxicity (DLT)	High grade hematologic or non-hematologic toxicities with exceptions and/or toxicities leading to treatment discontinuation will be regarded as DLT.	Up To Day 22
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. 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. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines and ocular events will be graded using the alternative scale provided in the protocol.	Up to 1 year 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have a partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version 1.1 response criteria without evidence of bone progression according to prostate cancer working group 3 (PCWG3).	Up to 1 year 2 months
Prostate-Specific Antigen (PSA) Response Rate	PSA response rate is defined as the percentage of participants with a decline of PSA of 50% or more from baseline.	Up to 1 year 2 months
Duration of Response (DOR)	DOR will be calculated among responders (PR or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3 or RECIST version 1.1 response criteria, or death due to any cause, whichever occurs first.	Up to 1 year 2 months
Radiographic Progression-Free Survival (rPFS)	rPFS is defined as the time from the date of first dose of pasritamig or JNJ-86974680 until the date of radiographic disease progression or death, whichever comes first.	Up to 1 year 2 months
Time to Response (TTR)	TTR is defined for the responders as the time from the date of first dose of any study treatment to the date of first documented response.	Up to 1 year 2 months
Serum Concentration of Pasritamig	Serum samples will be analyzed to determine concentrations of pasritamig.	Up to 1 year 2 months
Plasma Concentration of JNJ-86974680	Plasma samples will be analyzed to determine concentrations of JNJ-86974680.	Up to 1 year 2 months
Number of Participants With Anti-Pasritamig Antibodies	Serum samples will be analyzed for the detection of anti-pasritamig antibodies using a validated assay method.	Up to 1 year 2 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): January 14, 2026
• Primary Completion (Estimated): January 7, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: December 22, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 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
• Other Study ID Numbers: 78278343PBPCR1005 (Other Identifier: Janssen Research & Development, LLC)

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 www.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