A Study of JNJ-80038114 in Participants With Advanced Stage Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine recommended phase 2 dose(s) (RP2Ds) of JNJ-80038114 in Part 1 (dose escalation) and to determine the safety at the RP2D(s) in Part 2 (dose expansion).

Official Title
-----------------
A Phase 1 Study of JNJ-80038114, a T-Cell Redirecting Agent Targeting Prostate Specific Membrane Antigen (PSMA), for Advanced Stage Prostate Cancer

Conditions
-----------------
Prostatic Neoplasms

Intervention / Treatment
-----------------
* Drug: JNJ-80038114


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Metastatic castration-resistant prostate cancer (mCRPC) with confirmed adenocarcinoma of the prostate as defined by Prostate Cancer Working Group 3 (PCWG3) Measurable or evaluable disease At least 1 prior treatment for mCRPC Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ functions as defined by certain laboratory values Must sign an informed consent form (ICF) Participants must agree to use a highly effective form of birth control as guided by the study doctor Exclusion Criteria: Concurrent anticancer therapy Severe or long-lasting side effects related to prior anticancer therapy Known allergies to JNJ-80038114 or its excipients Brain metastasis or known seizure history Significant infections or lung, heart or other medical conditions

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Participants will receive JNJ-80038114. The dose levels will be escalated based on the dose limiting toxicities (DLTs) evaluation by the study evaluation team (SET). | Drug: JNJ-80038114<br>* JNJ-80038114 will be administered.<br>|
| Experimental: Part 2: Dose Expansion<br>Participants will receive JNJ-80038114 at the recommended Phase 2 dose (RP2D) determined in Part 1. | Drug: JNJ-80038114<br>* JNJ-80038114 will be administered.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2: 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 2 Years 6 Months | 
| Parts 1 and 2: 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. Cytokine release syndrome (CRS) and associated neurologic toxicity events will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. | Up to 2 Years 6 Months | 
| Part 1: Number of Participants With Dose-Limiting Toxicity (DLT) | Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. | Up to 2 Years 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of JNJ-80038114 | Serum concentration of JNJ-80038114 will be determined. | Up to 2 Years 6 Months | 
| Systemic Cytokine Concentrations | Cytokine concentrations will be determined for biomarker assessment. | Up to 2 Years 6 Months | 
| Serum Prostate Specific Antigen (PSA) Concentration | Serum PSA concentration will be determined. | Up to 2 Years 6 Months | 
| Number of Participants With Antibodies to JNJ-80038114 | Serum samples will be analyzed for the detection of antibodies to JNJ-80038114 using a validated assay method. | Up to 2 Years 6 Months | 
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants who have a partial response (PR) or better according to Prostate Cancer Working Group 3 (PCWG3) response criteria. | Up to 2 Years 6 Months | 
| PSA Response Rate | PSA response rate is defined as the percentage of participants with a confirmed decline in PSA of 50 percent (%) or more from baseline. | Up to 2 Years 6 Months | 
| Duration of Response (DOR) | DOR is defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3 response criteria, or death due to any cause, whichever occurs first. | Up to 2 Years 6 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate cancer