A Study of JNJ-75229414 for Metastatic Castration-resistant Prostate Cancer Participants

NCT05022849 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR10897275229414MPC1001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to determine recommended Phase 2 dose (RP2D) regimen(s) of JNJ-75229414 in Part 1 (Dose Escalation and to determine safety at the RP2D regimen(s) in Part 2 (Dose Expansion).

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events (AEs)

  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.

  Up to 15 years 9 months

• Number of Participants with AEs by Severity

  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.

  Up to 15 years 9 months

• Part 1: Number of Participants with Dose-limiting Toxicity (DLT)

  Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

  Up to 28 days

Secondary Outcomes (10)

• Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414

  Up to 15 years 9 months

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-75229414

  Up to 15 years 9 months

• Area Under Plasma Concentration Versus Time Curve from Time Zero to t Time (AUC[0-t]) of JNJ-75229414

  Up to 15 years 9 months

• Peripheral T Cell Expansion and Persistence via Monitoring Chimeric Antigen Receptor T (CAR-T) Positive Cell Counts

  Up to 15 years 9 months

• Number of Participants With Presence of Anti-JNJ-75229414 Antibodies

  Up to 15 years 9 months

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

Participants will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by JNJ-75229414 IV infusion escalated sequentially with a targeted dose consistent with the dose required by the cohort being enrolled to determine recommended Phase 2 dose (RP2D) regimen(s). Additional, intermediate dose levels may be implemented based on the review of all available data including, but not limited to, safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) by the study evaluation team (SET). Participants may receive bridging therapy (anti-androgen receptor agents \[example, abiraterone, enzalutamide\] and radiotherapy, or chemotherapy \[example, docetaxel\]) if clinically indicated to maintain disease stability.

Drug: JNJ-75229414; Drug: Bridging Therapy

Part 2: Dose Expansion

EXPERIMENTAL

Participants will receive JNJ-75229414 for each RP2D regimen determined in Part 1.

Drug: JNJ-75229414; Drug: Bridging Therapy

Interventions

JNJ-75229414 DRUG

JNJ-75229414 infusion will be administered intravenously.

Also known as: KLK2 CAR-T Cells

Part 1: Dose Escalation; Part 2: Dose Expansion

Bridging Therapy DRUG

Bridging therapy including Anti-AR agents (example, abiraterone, enzalutamide) will be administered orally and radiotherapy, or chemotherapy (example, docetaxel) will be administered intravenously.

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histology: Metastatic CRPC (mCRPC) with histologic confirmation of adenocarcinoma. Metastatic CRPC with neuroendocrine features or mixed histology is excluded
• Prior Therapy: Prior treatment with at least 1 prior novel androgen receptor AR-targeted therapy (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), or at least 1 prior chemotherapy (example, docetaxel)
• Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or detectable prostate-specific antigen (PSA) levels based on local laboratory results
• Fertile participants must use a condom with spermicide during any sexual contact with a woman of childbearing potential, including pregnant women, from the time of signing the ICF until 1 year after receiving a JNJ-75229414 infusion. Vasectomized participants must agree to use a condom to protect any sexual partner from exposure to semen for 1 year after receiving the last dose of study drug. Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies

You may not qualify if:

• Prior Grade 4 Cytokine release syndrome (CRS) or Grade 3 or Grade 4 neurotoxicity related to any T cell redirection (Bispecific cluster of differentiation \[CD 3\])
• Prior Kallikrein 2 (KLK2)-targeted therapy
• Prior chimeric antigen receptor T cell (CAR-T) therapy
• Receiving systemic treatment less than or equal to (\<=) 6 months prior to signing informed consent) for any invasive malignancy other than prostate cancer unless approved by the sponsor. Bisphosphonates initiated greater than or equal to (\>=) 6 weeks prior signing informed consent are allowed
• Less than 2 weeks between last administration anti-androgen agents (example, abiraterone or enzalutamide), poly adenosine diphosphate-ribose polymerase (PARP) inhibitors (example, olaparib) or radiotherapy, and less than 3 weeks between last administration of cytotoxic chemotherapy (example, docetaxel), radionuclides (example, radium-223, lutetium-177-Prostate-specific membrane antigen \[PSMA\]-617) or an investigational agent, and apheresis

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (8)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

University Of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 26, 2021
• Study Start: September 28, 2021
• Primary Completion: March 11, 2026
• Study Completion: March 11, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8)