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

A Phase 1, Dose Escalation Study of JNJ-75229414, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against KLK2 for Metastatic Castration-Resistant Prostate Cancer

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: JNJ-75229414; Drug: Bridging Therapy

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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 Escalation; 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; JNJ-75229414 infusion will be administered intravenously.; Other Names: KLK2 CAR-T Cells; Drug: Bridging Therapy; Bridging therapy including Anti-AR agents (example, abiraterone, enzalutamide) will be administered orally and radiotherapy, or chemotherapy (example, docetaxel) will be administered intravenously.
Experimental: Part 2: Dose Expansion; Participants will receive JNJ-75229414 for each RP2D regimen determined in Part 1.	Drug: JNJ-75229414; JNJ-75229414 infusion will be administered intravenously.; Other Names: KLK2 CAR-T Cells; Drug: Bridging Therapy; Bridging therapy including Anti-AR agents (example, abiraterone, enzalutamide) will be administered orally and radiotherapy, or chemotherapy (example, docetaxel) will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414	Cmax is the maximum observed plasma concentration of JNJ-75229414.	Up to 15 years 9 months
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-75229414	Tmax is the actual sampling time to reach maximum observed plasma concentration 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	AUC(0-t) is the area under the plasma concentration versus time curve from time zero to 't' time.	Up to 15 years 9 months
Peripheral T Cell Expansion and Persistence via Monitoring Chimeric Antigen Receptor T (CAR-T) Positive Cell Counts	Peripheral T cell expansion and persistence via monitoring CAR-T positive cell counts will be reported.	Up to 15 years 9 months
Number of Participants With Presence of Anti-JNJ-75229414 Antibodies	Number of participants with antibodies to JNJ-75229414 will be reported.	Up to 15 years 9 months
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve a confirmed best overall response of Complete Response (CR) or Partial Response (PR) evaluated by an independent local radiology review based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Prostate Cancer Working Group 3 (PCWG3) criteria will be used to assess progressive bone metastases.	Up to 15 years 9 months
Disease Control Rate (DCR)	DCR is defined as the sum of CR, PR, and stable disease (SD).	Up to 15 years 9 months
Duration of Response (DoR)	DoR is defined as the time from the date of first documented responses until date of documented progression or death whichever comes first.	Up to 15 years 9 months
Time to response (TTR)	TTR defined as the time from the date of first dose of study drug to the date of first documented response.	Up to 15 years 9 months
Peripheral Blood Quantitation of Vesicular Stomatitis Virus G glycoprotein (VSV-G) Copy Numbers	Peripheral blood quantitation of VSV-G copy numbers will be reported.	Up to 15 years 9 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): September 28, 2021
• Primary Completion (Estimated): July 3, 2024
• Study Completion (Estimated): June 30, 2037

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CR108972; 75229414MPC1001 (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 the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/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