A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer
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 and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion).
Arms and Interventions
|Experimental: Part 1: Dose Escalation|
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.
Participants will receive IV injection of JNJ-69086420.
|Experimental: Part 2: Dose Expansion|
Participants will receive intravenous (IV) injection of JNJ-69086420 at one of the RP2D(s) determined in Part 1.
Participants will receive IV injection of JNJ-69086420.
Primary Outcome Measures
- Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [Up to 2 years and 4 months]
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.
- Part 1: Number of Participants with Dose-Limiting Toxicity (DLT) [Up to 2 years and 4 months]
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.
- Part 1 and Part 2: Number of Participants with AEs by Severity [Up to 2 years and 4 months]
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.
Secondary Outcome Measures
- Percentage of Participants with Prostate Specific Antigen (PSA) Response [Week 12]
PSA response rate is defined as the percentage of participants with a decline of PSA of 50 percent (%) or more from baseline at Week 12.
- Overall Response Rate (ORR) [Up to 2 years and 4 months]
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).
- Maximum Observed Serum Concentration/Radioactivity (Cmax) of JNJ-69086420 [Up to 2 years and 4 months]
Cmax is defined as the maximum observed serum concentration/radioactivity of JNJ-69086420.
- Time to Reach Maximum Observed Serum Concentration/Radioactivity (Tmax) of JNJ-69086420 [Up to 2 years and 4 months]
Tmax is defined as time to reach maximum observed serum concentration/radioactivity of JNJ-69086420.
- Area Under the Serum Concentration-time Curve From Time Zero to t Time (AUC[0-t]) of JNJ-69086420 [Up to 2 years and 4 months]
AUC(0-t) is defined as the area under the serum concentration-time curve from time zero to t of JNJ-69086420.
- Number of Participants With Anti-JNJ-69086420 Antibodies [Up to 2 years and 4 months]
Number of participants with anti-JNJ-69086420 antibodies will be assessed to evaluate the potential immunogenicity.
Histologic: metastatic castration-resistant prostate cancer (mCRPC) with histologic confirmation of adenocarcinoma. Adenocarcinoma with small-cell or neuroendocrine features is allowed
Must have had prior exposure to at least one novel androgen receptor (AR) targeted therapy (example, abiraterone acetate, enzalutamide, apalutamide, darolutamide); prior taxane or other chemotherapy is acceptable but not required
Treatment with other agents for prostate cancer, if received, must have been discontinued greater than or equal to (>=) 2 weeks prior to first dose of study drug.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ functions as reflected in laboratory parameters
Part 1: Prior treatment with radium Xofigo (Ra 223 dichloride), strontium, or samarium therapy or radioconjugate therapy
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.
Contacts and Locations
|1||City of Hope||Duarte||California||United States||91010|
|2||UCLA Medical Center||Los Angeles||California||United States||90095|
|3||University of California San Francisco||San Francisco||California||United States||94158-2549|
|4||University of Chicago||Chicago||Illinois||United States||60637|
|5||Tulane School Of Medicine||New Orleans||Louisiana||United States||70112|
|6||Urology Cancer Center and GU Research Network||Omaha||Nebraska||United States||68130|
|7||Memorial Sloan Kettering Cancer Center||New York||New York||United States||10065|
Sponsors and Collaborators
- Janssen Research & Development, LLC
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)None provided.