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

Primary Purpose

Prostatic Neoplasms

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
JNJ-75229414
Bridging Therapy
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Prostatic Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Cancer Center
  • Norton Cancer Institute
  • University Of Minnesota
  • Icahn School of Medicine at Mount Sinai
  • Columbia University Medical Center
  • Levine Cancer Institute
  • University of Pennsylvania
  • University of Utah Huntsman Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: Dose Escalation

Part 2: Dose Expansion

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414
Cmax is the maximum observed plasma concentration of JNJ-75229414.
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.
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.
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.
Number of Participants With Presence of Anti-JNJ-75229414 Antibodies
Number of participants with antibodies to JNJ-75229414 will be reported.
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.
Disease Control Rate (DCR)
DCR is defined as the sum of CR, PR, and stable disease (SD).
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.
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.
Peripheral Blood Quantitation of Vesicular Stomatitis Virus G glycoprotein (VSV-G) Copy Numbers
Peripheral blood quantitation of VSV-G copy numbers will be reported.

Full Information

First Posted
August 20, 2021
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05022849
Brief Title
A Study of JNJ-75229414 for Metastatic Castration-resistant Prostate Cancer Participants
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 28, 2021 (Actual)
Primary Completion Date
July 3, 2024 (Anticipated)
Study Completion Date
June 30, 2037 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose Escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2: Dose Expansion
Arm Type
Experimental
Arm Description
Participants will receive JNJ-75229414 for each RP2D regimen determined in Part 1.
Intervention Type
Drug
Intervention Name(s)
JNJ-75229414
Other Intervention Name(s)
KLK2 CAR-T Cells
Intervention Description
JNJ-75229414 infusion will be administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Bridging Therapy
Intervention Description
Bridging therapy including Anti-AR agents (example, abiraterone, enzalutamide) will be administered orally and radiotherapy, or chemotherapy (example, docetaxel) will be administered intravenously.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Up to 15 years 9 months
Title
Number of Participants with AEs by Severity
Description
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.
Time Frame
Up to 15 years 9 months
Title
Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
Description
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.
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414
Description
Cmax is the maximum observed plasma concentration of JNJ-75229414.
Time Frame
Up to 15 years 9 months
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-75229414
Description
Tmax is the actual sampling time to reach maximum observed plasma concentration of JNJ-75229414.
Time Frame
Up to 15 years 9 months
Title
Area Under Plasma Concentration Versus Time Curve from Time Zero to t Time (AUC[0-t]) of JNJ-75229414
Description
AUC(0-t) is the area under the plasma concentration versus time curve from time zero to 't' time.
Time Frame
Up to 15 years 9 months
Title
Peripheral T Cell Expansion and Persistence via Monitoring Chimeric Antigen Receptor T (CAR-T) Positive Cell Counts
Description
Peripheral T cell expansion and persistence via monitoring CAR-T positive cell counts will be reported.
Time Frame
Up to 15 years 9 months
Title
Number of Participants With Presence of Anti-JNJ-75229414 Antibodies
Description
Number of participants with antibodies to JNJ-75229414 will be reported.
Time Frame
Up to 15 years 9 months
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 15 years 9 months
Title
Disease Control Rate (DCR)
Description
DCR is defined as the sum of CR, PR, and stable disease (SD).
Time Frame
Up to 15 years 9 months
Title
Duration of Response (DoR)
Description
DoR is defined as the time from the date of first documented responses until date of documented progression or death whichever comes first.
Time Frame
Up to 15 years 9 months
Title
Time to response (TTR)
Description
TTR defined as the time from the date of first dose of study drug to the date of first documented response.
Time Frame
Up to 15 years 9 months
Title
Peripheral Blood Quantitation of Vesicular Stomatitis Virus G glycoprotein (VSV-G) Copy Numbers
Description
Peripheral blood quantitation of VSV-G copy numbers will be reported.
Time Frame
Up to 15 years 9 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
University Of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Utah Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States

12. IPD Sharing Statement

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

Learn more about this trial

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

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