A Study of JNJ-87189401 Plus JNJ-78278343 for Advanced Prostate Cancer

Study Overview
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Brief Summary
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The purpose of the study is to determine the recommended regimen for Phase 2 (RP2Rs) of combination of JNJ-87189401 with JNJ-78278343 (Part 1: dose escalation) and further evaluate the safety at RP2Rs (Part 2: dose expansion) in participants with advanced prostate cancer.

Official Title
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A Phase 1 Study of JNJ-87189401 (PSMA-CD28 Bispecific Antibody) Combined With JNJ-78278343 (KLK2-CD3 Bispecific Antibody) for Advanced Prostate Cancer

Conditions
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Advanced Prostate Cancer

Intervention / Treatment
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* Drug: JNJ-78278343
* Drug: JNJ-87189401


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic castration-resistant prostate cancer (mCRPC) as defined by Prostate Cancer Working Group 3 (PCWG3): Histologically confirmed adenocarcinoma of the prostate. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted. However, small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed Measurable or evaluable disease per PCWG3 criteria; all participants must have a serum PSA value greater than or equal to (>=2) nanograms per milliliter (ng/mL) at time of screening Prior orchiectomy or medical castration; participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), prior to the first dose of study drug and must continue this therapy throughout the treatment phase Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications (example, chronic corticosteroids, methotrexate, or tacrolimus) Any of the following within 6 months prior to signature of informed consent: a. myocardial infarction, b. severe or unstable angina, c. clinically significant ventricular arrhythmias, d. congestive heart failure (New York Heart Association [NYHA] class II to IV), e. transient ischemic attack, and f. Cerebrovascular accident

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)<br>Participants will receive JNJ-78278343+JNJ-87189401 escalated sequentially in Part 1 to select a recommended Phase 2 regimen (RP2R). Participants will receive the combination treatment at the RP2R in Part 2 (dose expansion). | Drug: JNJ-78278343<br>* JNJ-78278343 will be administered.<br>* Other names: KLK2-CD3;Drug: JNJ-87189401<br>* JNJ-87189401 will be administered.<br>* Other names: PSMAxCD28;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants With Dose Limiting Toxicity (DLT) | DLTs are specific adverse events (AEs) and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity. | Up to 21 days after first combination dose of study drugs | 
| Part 1 and Part 2: Number of Participants with Adverse Events (AEs) by Severity | 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. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome events, which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 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 years 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Serum Concentration of JNJ-87189401 | Serum samples will be analyzed to determine concentrations of JNJ-87189401. | Up to 3 years 7 months | 
| Number of Participants With Antibodies to JNJ-87189401 and JNJ-78278343 | Number of participants with antibodies to JNJ-87189401 and JNJ-78278343 will be reported. | Up to 3 years 7 months | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants who have a partial response (PR) or better according to response evaluation criteria in solid tumors (RECIST) version 1.1 without evidence of bone progression according to Prostate Cancer Working Group 3 (PCWG3). | Up to 3 years 7 months | 
| Prostate Specific Antigen (PSA) Response Rate | PSA response rate is defined as the percentage of participants with a confirmed decline of PSA of 50 percent (%) or more from baseline. | Up to 3 years 7 months | 
| Duration of Response (DOR) | DOR is defined for participants who achieved response (PR or better) as the time between the date of initial documentation of response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3, or death due to any cause, whichever occurs first. | Up to 3 years 7 months |