A Study of JNJ-78278343 in Combination With JNJ-63723283 (Cetrelimab) for Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to identify the recommended phase 2 doses (RP2Ds) of JNJ-78278343 with cetrelimab (JNJ-63723283) in Part 1 (dose escalation) and to determine safety at the RP2D(s) in Part 2 (dose expansion).

Official Title
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A Phase 1b Study of JNJ-78278343, a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2), in Combination With JNJ-63723283 (Cetrelimab) for Metastatic Castration-Resistant Prostate Cancer

Conditions
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Metastatic Castration-resistant Prostate Neoplasms

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


Participation Criteria
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Eligibility Criteria
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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. Prior treatment for mCRPC with at least 1 prior novel androgen receptor-targeted therapy (ie, abiraterone acetate, apalutamide, enzalutamide, darolutamide), or chemotherapy (eg, docetaxel) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ functions Exclusion Criteria: Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications Toxicity related to prior anticancer therapy that has not returned to Grade less than or equal to (<=) 1 or baseline levels (except for alopecia, vitiligo, Grade <=2 peripheral neuropathy) Solid organ or bone marrow transplantation Known allergies, hypersensitivity, or intolerance to any of the components (eg, excipients) of JNJ-78278343 or cetrelimab Significant infections or serious lung, heart or other medical conditions

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: JNJ-78278343 + Cetrelimab: Part 1 (Dose Escalation) and Part 2 (Dose Expansion)<br>Participants will receive subcutaneous (SC) administration of JNJ-78278343 in combination with intravenous (IV) infusion of cetrelimab during Part 1 (dose escalation). The dose of JNJ-78278343 will be escalated sequentially until a recommended phase 2 dose (RP2D). Participants will receive the combination treatment at the RP2D in Part 2 (dose expansion) | Drug: JNJ-78278343<br>* JNJ-78278343 will be administered subcutaneously.<br>Drug: Cetrelimab<br>* Cetrelimab will be administered by intravenous infusion.<br>* Other names: JNJ-63723283;|

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 and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity. | Up to 21 days after first dose of cetrelimab | 
| 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. | Up to 2 years 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who have a partial response (PR) or better without evidence of bone progression according to Prostate Cancer Working Group 3 (PCWG3) criteria. | Up to 2 years 10 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 2 years 10 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 2 years 10 months |