A Study of Pasritamig (JNJ-78278343) in Combination With Other Agents for Metastatic Prostate Cancer

A Phase 1b Study of JNJ-78278343, Targeting Human Kallikrein 2 (KLK2) in Combination With Other Agents for Metastatic Prostate Cancer

The purpose of this study is to identify the recommended phase 2 regimen(s) RP2R(s) of pasritamig and combination regimens in Part 1 (dose escalation) and to determine safety at the putative RP2R(s) of pasritamig with the combination regimens in Part 2 (dose expansion).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Hormone-sensitive Prostate Cancer; Metastatic Castration-resistant Prostate Neoplasms
• Intervention / Treatment: Drug: Enzalutamide; Drug: Apalutamide; Drug: Cetrelimab; Drug: Cabazitaxel; Drug: Docetaxel; Drug: Darolutamide; Drug: Abiraterone acetate plus prednisone (AAP); Drug: Pasritamig; Drug: Lutetium Lu-177 vipivotide tetraxetan; Drug: JNJ-101556143

• Study Type: Interventional
• Enrollment (Estimated): 300
• 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

• Australia
  • Kurralta Park, Australia, 5037
    • Recruiting
    • Icon Cancer Centre Kurralta Park
  • Macquarie University, Australia, 2109
    • Recruiting
    • Macquarie University
  • Melbourne, Australia, 3000
    • Recruiting
    • Peter MacCallum Cancer Centre
  • Woolloongabba, Australia, 4102
    • Recruiting
    • Princess Alexandra Hospital
• Spain
  • Barcelona, Spain, 8035
    • Recruiting
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hosp Univ Hm Sanchinarro
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • Brooklyn, New York, United States, 11223
      • Recruiting
      • Perlmutter Cancer Center at NYU Langone Brooklyn
    • Mineola, New York, United States, 11501
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Hospital - Long Island
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Sidney Kimmel Cancer Center - Jefferson Health

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Part 1 A-G, 1I, 1J, and 1K (all combination treatments) and Parts 2B-C (cabazitaxel, docetaxel): Metastatic castration-resistant prostate cancer (mCRPC) with confirmed adenocarcinoma of the prostate as defined by prostate cancer working group 3 (PCWG3); Parts 2D-G, 2I, 2J, and 2K (apalutamide, enzalutamide, darolutamide, abiraterone acetate + prednisone [AAP], lutetium Lu-177 vipivotide tetraxetan, JNJ-101556143): mCRPC: Histologically confirmed adenocarcinoma of the prostate as defined by PCWG3, with a minimum PSA of 2 nanogram [ng]/milliliter (mL); Part 2H (apalutamide): metastatic hormone-sensitive prostate cancer(mHSPC) with PSA greater than (>) 0.2 ng/mL on 6 to 24 months of treatment with a next generation ARPI (apalutamide, enzalutamide, darolutamide, or abiraterone)
• Measurable or evaluable disease, except for Part 2H
• (a) Part 1A (cetrelimab) - Prior treatment for mCRPC with at least 1 prior androgen receptor pathway inhibitors (ARPI) (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), or chemotherapy (example, docetaxel). (b) Part 1C and 2C (docetaxel), Part 1D (apalutamide), Part 1E and 2E (enzalutamide), Part 1F and 2F (darolutamide), and Part 1G, 2G (AAP), and Part 1K & 2K (JNJ-101556143)- Prior treatment with at least 1 prior ARPI (that is, apalutamide, enzalutamide, darolutamide, or abiraterone acetate). (C) Part 1B and 2B (cabazitaxel) - Prior treatment with at least 1 prior ARPI (ie, abiraterone acetate, apalutamide, enzalutamide, darolutamide) and docetaxel. (d) Part 2D (apalutamide) - Prior treatment with at least 1 prior ARPI (e) Part 2H (apalutamide)- Participant may have received up to 6 cycles of docetaxel. The last dose of docetaxel must be administered at least 2 months prior to enrollment (f) Parts 1I, 1J, 2I & 2J (lutetium Lu-177 vipivotide tetraxetan)- Prior treatment with at least 1 ARPI (abiraterone acetate, enzalutamide, darolutamide, or apalutamide). Participant must not have received prior cytotoxic chemotherapy or prior radioligand therapy (RLT) for mCRPC
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ functions

Exclusion Criteria:

• Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications
• Toxicity related to prior anticancer therapy that has not returned to Grade less than or equal to (<=) 1 or baseline levels (except for alopecia, vitiligo, Grade <=2 peripheral neuropathy)
• Solid organ or bone marrow transplantation
• Known allergies, or intolerance to any of the components (example, excipients) of pasritamig, cetrelimab (Part 1A), cabazitaxel, Part 1B and 2B , docetaxel Part 1C and 2C , apalutamide (Part 1D and 2D and Part 2H), enzalutamide (Part 1E and 2E), darolutamide (Part 1F and 2F), or AAP (Part 1G and 2G), lutetium Lu-177 vipivotide tetraxetan (Parts 1I, 1J, 2I, and 2J), or JNJ-101556143 (Parts 1K & 2K)
• Significant infections or serious lung, heart or other medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JNJ-78278343 + Combination agent: Part 1 (Dose Escalation) and Part 2 (Dose Expansion); Participants will receive pasritamig (JNJ-78278343) and combination agent (cetrelimab, cabazitaxel, docetaxel, apalutamide, enzalutamide, Darolutamide, abiraterone acetate plus prednisone, Lutetium Lu-177 vipivotide tetraxetan and JNJ-101556143) during Part 1 (dose escalation). The dose of pasritamig (JNJ-78278343) will be escalated sequentially until a recommended phase 2 regimen (RP2R). Participants will receive pasritamig (JNJ-78278343) and combination agent treatment at the putative RP2R in Part 2 (dose expansion).

Drug: Enzalutamide; Enzalutamide will be administered orally.; Drug: Apalutamide; Apalutamide will be administered orally.; Drug: Cetrelimab; Cetrelimab will be administered by intravenous infusion.; Other Names: JNJ-63723283; Drug: Cabazitaxel; Cabazitaxel will be administered by intravenous infusion.; Drug: Docetaxel; Docetaxel will be administered by intravenous infusion.; Drug: Darolutamide; Darolutamide will be administered orally.; Drug: Abiraterone acetate plus prednisone (AAP); Abiraterone acetate plus prednisone (AAP) will be administered orally.; Drug: Pasritamig; Pasritamig will be administered.; Other Names: JNJ-78278343; Drug: Lutetium Lu-177 vipivotide tetraxetan; Lutetium Lu-177 vipivotide tetraxetan will be administered intravenously.; Drug: JNJ-101556143; JNJ-101556143 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)	DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity.	Up to 21 days after first dose of combination agent
Part 1 and Part 2: 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 2 years 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who have a partial response (PR) or better without evidence of bone progression according to Prostate Cancer Working Group 3 (PCWG3) criteria.	Up to 2 years 11 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 2 years 11 months
Time to Response (TTR)	TTR is defined for the responders as the time from the date of first dose of to the date of first documented response that is subsequently confirmed.	Up to 2 years 11 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 2 years 11 months
Radiographic Progression-free Survival (rPFS)	rPFS is defined time from the date of first dose of pasritamig until the date of objective disease progression or death, whichever comes first.	Up to 2 years 11 months
Part 2H Metastatic hormone-sensitive prostate cancer (mHSPC) Participants : Composite Progression-Free Survival (PFS)	Composite PFS is defined as time from start of treatment to the date of first occurrence of investigator determined disease progression (Response Evaluation Criteria in Solid Tumors [RECIST] or bone progression), pain, PSA progression, death or last disease assessment.	Up to 2 years 11 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): April 26, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): May 23, 2028

Study Registration Dates

• First Submitted: April 6, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 19, 2023

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; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Polycyclic Compounds; Taxoids; Cyclodecanes; Diterpenes; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Androstenes; Androstanes; Docetaxel; Abiraterone Acetate; Prednisone; darolutamide; enzalutamide; cabazitaxel; apalutamide
• Other Study ID Numbers: CR109321; 78278343PCR1003 (Other Identifier: Janssen Research & Development, LLC); 2022-503132-14-00 (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