A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of JNJ-69086420 in Part 1 (Dose Escalation) and to determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion).

Official Title
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A Phase 1 Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer

Conditions
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Prostatic Neoplasms, Adenocarcinoma

Intervention / Treatment
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* Drug: JNJ-69086420


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic castration resistant prostate cancer (mCRPC) with histologic confirmation of adenocarcinoma (adenocarcinoma with small-cell or neuroendocrine features is allowed) with prior exposure to at least one androgen receptor (AR) targeted therapy (example, abiraterone acetate, enzalutamide, apalutamide, darolutamide). In addition: Part 1: prior taxane or other chemotherapy is acceptable but not required. Part 2a: prior taxane or other chemotherapy required, Part 2b: no prior taxane or other chemotherapy, Part 2c: mCRPC that has progressed after prior treatment with lutetium Lu-177 vipivotide tetraxetan Prior orchiectomy or medical castration; or, for 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 Palliative radiotherapy (for example [eg], soft tissue lesions) must be completed greater than (>) 2 weeks prior to start of study drug except for palliative radiotherapy for pain (eg, bone pain), which may be used any time prior to first dose Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ functions as reflected in laboratory parameters Exclusion Criteria: Prior treatment with radium Xofigo (Ra 223 dichloride), strontium, samarium, or other radioconjugate therapy. In addition: Part 2b: Prior treatment with chemotherapy (eg, docetaxel) or poly ADP ribose polymerase (PARP) inhibitors. Part 2c: Prior treatment with lutetium Lu-177 vipivotide tetraxetan is permitted Known history of myelodysplastic syndrome, leukemia, or hematological malignancy with features suggestive of myelodysplastic syndrome/acute myeloid leukemia at any timepoint Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia, radiation tissue fibrosis, or peripheral neuropathy) Known allergies, hypersensitivity, or intolerance to JNJ-69086420 or its excipients and protein therapeutics Active or chronic hepatitis B or hepatitis C infection

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
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 intravenous (IV) injection of JNJ-69086420 with one or multiple doses. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. | Drug: JNJ-69086420<br>* Participants will receive IV injection of JNJ-69086420.<br>* Other names: Actinium-225-DOTA-h11B6;|
| Experimental: Part 2: Dose Expansion<br>Participants in one or more cohorts will receive intravenous (IV) injection of JNJ-69086420 at the RP2D(s) determined in Part 1. | Drug: JNJ-69086420<br>* Participants will receive IV injection of JNJ-69086420.<br>* Other names: Actinium-225-DOTA-h11B6;|

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. | Up to 2 years and 4 months | 
| 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. | Up to 2 years and 4 months | 
| Part 1 and Part 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. | Up to 2 years and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Prostate Specific Antigen (PSA) Response | PSA response rate is defined as the percentage of participants with a decline of PSA of 50 percent (%) or more from baseline and that is subsequently confirmed. | Up to 2 years and 4 months | 
| Overall Response Rate (ORR) | ORR is defined as the percentage 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 2 years and 4 months | 
| Maximum Observed Serum Concentration/Radioactivity (Cmax) of JNJ-69086420 | Cmax is defined as the maximum observed serum concentration/radioactivity of JNJ-69086420. | Up to 2 years and 4 months | 
| Time to Reach Maximum Observed Serum Concentration/Radioactivity (Tmax) of JNJ-69086420 | Tmax is defined as time to reach maximum observed serum concentration/radioactivity of JNJ-69086420. | Up to 2 years and 4 months | 
| Area Under the Serum Concentration-time Curve From Time Zero to t Time (AUC[0-t]) of JNJ-69086420 | AUC(0-t) is defined as the area under the serum concentration-time curve from time zero to t of JNJ-69086420. | Up to 2 years and 4 months | 
| Number of Participants With Anti-JNJ-69086420 Antibodies | Number of participants with anti-JNJ-69086420 antibodies will be assessed to evaluate the potential immunogenicity. | Up to 2 years and 4 months |