Clincosm LogoSign in Get a demo

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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05022849
Collaborator
(none)
60
Enrollment
11
Locations
2
Arms
50.7
Anticipated Duration (Months)
5.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 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 :
Sep 28, 2021
Anticipated Primary Completion Date :
Jul 3, 2024
Anticipated Study Completion Date :
Dec 19, 2025

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 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.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) [Up to 2 years and 10 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 [Up to 2 years and 10 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) [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 [Up to 2 years and 10 months]

      Cmax is the maximum observed plasma concentration of JNJ-75229414.

    2. Time to Reach Maximum Observe Plasma Concentration (Tmax) of JNJ-75229414 [Up to 2 years and 10 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 [Up to 2 years and 10 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 [Up to 2 years and 10 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 [Up to 2 years and 10 months]

      Number of participants with antibodies to JNJ-75229414 will be reported.

    6. Overall Response Rate (ORR) [Up to 2 years and 10 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) [Up to 2 years and 10 months]

      DCR is defined as the sum of CR, PR, and stable disease (SD).

    8. Duration of Response (DoR) [Up to 2 years and 10 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) [Up to 2 years and 10 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 [Up to 2 years and 10 months]

      Peripheral blood quantitation of VSV-G copy numbers will be reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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) or radiotherapy, and less than 3 weeks between last administration of cytotoxic chemotherapy (example, docetaxel) or an investigational agent, and apheresis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Cancer Center Duarte California United States 91010
    2 Cedars-Sinai Medical Center West Hollywood California United States 90048
    3 Emory University - Winship Cancer Institute Atlanta Georgia United States 30322
    4 Norton Cancer Institute Louisville Kentucky United States 40207
    5 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201
    6 University Of Minnesota Minneapolis Minnesota United States 55455
    7 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    8 Columbia University Medical Center New York New York United States 10032
    9 Levine Cancer Institute Charlotte North Carolina United States 28204
    10 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    11 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT05022849
    Other Study ID Numbers:
    • CR108972
    • 75229414MPC1001
    First Posted:
    Aug 26, 2021
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Prostatic Neoplasms

    Study Results

    No Results Posted as of Aug 3, 2022