Clinical trial NCT05022849: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Prostatic Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-08-26
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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).


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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 15 years 9 months
measure: Number of Participants with AEs by Severity
timeFrame: Up to 15 years 9 months
measure: Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Maximum Observe Plasma Concentration (Cmax) of JNJ-75229414
timeFrame: Up to 15 years 9 months
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-75229414
timeFrame: Up to 15 years 9 months
measure: Area Under Plasma Concentration Versus Time Curve from Time Zero to t Time (AUC[0-t]) of JNJ-75229414
timeFrame: Up to 15 years 9 months
measure: Peripheral T Cell Expansion and Persistence via Monitoring Chimeric Antigen Receptor T (CAR-T) Positive Cell Counts
timeFrame: Up to 15 years 9 months
measure: Number of Participants With Presence of Anti-JNJ-75229414 Antibodies
timeFrame: Up to 15 years 9 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 15 years 9 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 15 years 9 months
measure: Duration of Response (DoR)
timeFrame: Up to 15 years 9 months
measure: Time to response (TTR)
timeFrame: Up to 15 years 9 months
measure: Peripheral Blood Quantitation of Vesicular Stomatitis Virus G glycoprotein (VSV-G) Copy Numbers
timeFrame: Up to 15 years 9 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: