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

A Phase 1 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), to determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion), to determine safety of JNJ-69086420 at the RP2D(s) as a combination therapy in Part 3 (combination therapy) and to determine safety of JNJ-69086420 at the RP2D(s) in participants with metastatic hormone-sensitive prostate cancer (mHSPC) in Part 4.

Study Overview

• Status: Active, not recruiting
• Conditions: Adenocarcinoma; Prostatic Neoplasms
• Intervention / Treatment: Drug: JNJ-69086420; Drug: JNJ-78278343; Radiation: Stereotactic body radiation therapy

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Hospital & Clinics
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • XCancer Omaha / Urology Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For Part 1, Part 2, Part 3: 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 (for example [e.g.], 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, with or without prior chemotherapy, Part 3: prior taxane or other chemotherapy is acceptable but not required & For Part 4a: metastatic HSPC, For Part 4b: disease that can be treated with less than or equal to (<=) 5 radiation fields and no visceral metastases
• Parts 1, 2 & 3: 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. This criterion does not apply to Part 4
• Palliative radiotherapy (e.g. soft tissue lesions) must be completed greater than (>) 2 weeks prior to start of study drug except for palliative radiotherapy for pain (e.g., 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, other systemic anti-neoplastic therapy <=30 days prior to the first dose of study drug except for luteinizing hormone-releasing hormone agonists/antagonists or GnRH agonists/antagonists. Novel androgen axis drugs <=14 days prior to the first dose of study drug. In addition: Part 2b: Must not have received prior treatment with chemotherapy (eg, docetaxel) or poly ADP ribose polymerase (PARP) inhibitors, Part 2c: Prior treatment with lutetium Lu-177 vipivotide tetraxetan is required, but must have been completed >42 days prior to first dose of study drug, Part 3: Must not have received prior treatment with JNJ-78278343, Part 4: Must not have received ADT or AR-targeted therapy less than or equal to (<=) 56 days prior to first dose of study drug
• 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 <= 1 (except alopecia, radiation tissue fibrosis, or peripheral neuropathy)
• Known allergies, hypersensitivity, or intolerance to JNJ-69086420 or its excipients and protein therapeutics. For Part 3, known allergies, hypersensitivity, or intolerance to JNJ-78278343 or its excipients or protein therapeutics
• Active or chronic hepatitis B or hepatitis C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Participants will receive 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; Participants will receive JNJ-69086420.; Other Names: Actinium-225-DOTA-h11B6
Experimental: Part 2: Dose Expansion; Participants in one or more cohorts will receive JNJ-69086420 at the RP2D(s) determined in Part 1.	Drug: JNJ-69086420; Participants will receive JNJ-69086420.; Other Names: Actinium-225-DOTA-h11B6
Experimental: Part 3: Combination Therapy; Participants will receive JNJ-69086420 at the determined RP2D(s) and fixed dose of JNJ-78278343.	Drug: JNJ-69086420; Participants will receive JNJ-69086420.; Other Names: Actinium-225-DOTA-h11B6; Drug: JNJ-78278343; Participants will receive JNJ-78278343.
Experimental: Part 4: HSPC Expansion; Participants with HSPC will receive JNJ-69086420 at the RP2D(s) in Part 4(a), and JNJ-69086420 following stereotactic body radiation therapy in Part 4(b).	Drug: JNJ-69086420; Participants will receive JNJ-69086420.; Other Names: Actinium-225-DOTA-h11B6; Radiation: Stereotactic body radiation therapy; Participants will receive stereotactic body radiaition therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Part 3: Serum Concentration of JNJ-78278343	Venous blood samples will be collected for assessment of serum concentrations of JNJ-78278343.	Up to 2 years and 4 months
Part 3:Number of Participants With Anti-JNJ-78278343 Antibodies	Number of participants with anti-JNJ-78278343 antibodies will be assessed to evaluate the potential immunogenicity.	Up to 2 years and 4 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Lehner F, Salemi S, Millan C, Kundig C, Eberli D. Inhibition of Growth and Induction of Apoptosis of Human Prostate Cancer Cells by Enzymatic Blockage of Kallikreins. Prostate Cancer. 2026 Jan 11;2026:7871208. doi: 10.1155/proc/7871208. eCollection 2026.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Estimated): December 8, 2026
• Study Completion (Estimated): December 8, 2026

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: CR108817; 69086420PCR1001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No