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

• ClinicalTrials.gov Identifier: NCT05022849
• Recruitment Status: Active, not recruiting
• First Posted: August 26, 2021
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Prostatic Neoplasms	Drug: JNJ-75229414; Drug: Bridging Therapy	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: September 28, 2021
• Estimated Primary Completion Date: July 3, 2024
• Estimated Study Completion Date: June 30, 2037

Arms and Interventions

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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 15 years 9 months ]
   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.
2. Number of Participants with AEs by Severity [ Time Frame: Up to 15 years 9 months ]
   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.
3. Part 1: Number of Participants with Dose-limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]
   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.

Secondary Outcome Measures :

1. Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414 [ Time Frame: Up to 15 years 9 months ]
   Cmax is the maximum observed plasma concentration of JNJ-75229414.
2. Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-75229414 [ Time Frame: Up to 15 years 9 months ]
   Tmax is the actual sampling time to reach maximum observed plasma concentration of JNJ-75229414.
3. Area Under Plasma Concentration Versus Time Curve from Time Zero to t Time (AUC[0-t]) of JNJ-75229414 [ Time Frame: Up to 15 years 9 months ]
   AUC(0-t) is the area under the plasma concentration versus time curve from time zero to 't' time.
4. Peripheral T Cell Expansion and Persistence via Monitoring Chimeric Antigen Receptor T (CAR-T) Positive Cell Counts [ Time Frame: Up to 15 years 9 months ]
   Peripheral T cell expansion and persistence via monitoring CAR-T positive cell counts will be reported.
5. Number of Participants With Presence of Anti-JNJ-75229414 Antibodies [ Time Frame: Up to 15 years 9 months ]
   Number of participants with antibodies to JNJ-75229414 will be reported.
6. Overall Response Rate (ORR) [ Time Frame: Up to 15 years 9 months ]
   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.
7. Disease Control Rate (DCR) [ Time Frame: Up to 15 years 9 months ]
   DCR is defined as the sum of CR, PR, and stable disease (SD).
8. Duration of Response (DoR) [ Time Frame: Up to 15 years 9 months ]
   DoR is defined as the time from the date of first documented responses until date of documented progression or death whichever comes first.
9. Time to response (TTR) [ Time Frame: Up to 15 years 9 months ]
   TTR defined as the time from the date of first dose of study drug to the date of first documented response.
10. Peripheral Blood Quantitation of Vesicular Stomatitis Virus G glycoprotein (VSV-G) Copy Numbers [ Time Frame: Up to 15 years 9 months ]
    Peripheral blood quantitation of VSV-G copy numbers will be reported.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

City of Hope Cancer Center

Duarte, California, United States, 91010

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40207

United States, Minnesota

University Of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

Levine Cancer Institute

Charlotte, North Carolina, United States, 28204

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Utah

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT05022849
• Other Study ID Numbers: CR108972; 75229414MPC1001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: August 26, 2021
• Last Update Posted: April 24, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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
• URL: https://www.janssen.com/clinical-trials/transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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