A Study of JNJ-63898081 in Participants With Advanced Stage Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study are to determine the recommended Phase 2 dose (RP2D) regimen and the maximum tolerated dose, and to determine the safety of JNJ-63898081.

Official Title
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A Phase 1, First-in-Human, Dose Escalation Study of JNJ-63898081, in Subjects With Advanced Stage Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: JNJ-63898081


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histology: Part 1: Metastatic castration-resistant prostate cancer (mCRPC) with histologic confirmation of adenocarcinoma. Adenocarcinoma with small-cell or neuroendocrine features is allowed. mCRPC is defined by prostate Cancer Working Group (PCWG )3 criteria. Part 2: mCRPC as defined above or pathologically confirmed metastatic renal cell carcinoma (RCC) as defined by world health organization (WHO) 2016 Classifications Measurable or evaluable disease: Part 1: Either measurable or evaluable disease for prostate cancer. Part 2: At least one measurable lesion as per RECIST v1.1. Evidence of disease progression on prior therapy that requires a new line of treatment Participants with accessible lesions enrolled in selected pharmacokinetic (PK)/pharmacodynamics (PD) cohorts and in Part 2 must agree to undergo the mandatory fresh tumor biopsies, unless collection of the biopsy presents a safety risk Exclusion Criteria: Less than 2 weeks between prior anticancer treatment (including radiotherapy) discontinuation and the first dose of study drug, and toxicities have not returned to Grade less than or equal to (<=) 1 or baseline Prior treatment with prostate-specific membrane antigen (PSMA)-targeted therapy except for PSMA-targeted vaccine is permitted Solid organ or bone marrow transplantation Seizure or known condition that may predispose to seizure or intracranial masses Other active malignancy requiring systemic treatment <=12 months prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
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 with metastatic castration-resistant prostate cancer (mCRPC) will receive JNJ-63898081. Ascending dose levels will be sequentially tested. | Drug: JNJ-63898081<br>* JNJ-63898081 will be administered.<br>|
| Experimental: Part 2: Dose Expansion<br>Participants with mCRPC or renal cell carcinoma (RCC) will receive JNJ-63898081 at the recommended Phase 2 dose (RP2D) determined in Part 1. | Drug: JNJ-63898081<br>* JNJ-63898081 will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | 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. | Approximately 3 years | 
| 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. | Approximately 3 years | 
| Part 1: Severity of Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) | Severity of AEs has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; Grade 5: Death. | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Serum Concentrations of JNJ-63898081 | Serum samples will be analyzed to determine concentrations of JNJ-63898081 using a validated method. | Approximately 3 years | 
| Part 1 and 2: Systemic Cytokine Concentrations | A panel of cytokines, including those proinflammatory ones, will be measured. | Approximately 3 years | 
| Part 1 and 2: Number of Participants with JNJ-63898081 Antibodies | Anti-JNJ-63898081 antibodies will be evaluated in serum samples collected from all participants. | Approximately 3 years | 
| Serum Prostate Specific Antigen (PSA) Concentration | Serum prostate specific antigen (PSA) concentration will be assessed. | Approximately 3 years | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants who have a PR or better according to the disease-specific response criteria. Evaluation of prostate treatment response will be performed according to Prostate Cancer Working Group 3 (PCWG3). | Approximately 3 years | 
| Duration of Response | Duration of response (DOR) will be calculated 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 disease-specific response criteria, or death due to any cause, whichever occurs first. Evaluation of prostate treatment response will be performed according to Prostate Cancer Working Group 3 (PCWG3). | Approximately 3 years |