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

NCT04644770 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CR10881769086420PCR1001
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Prostatic Neoplasms; Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• 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

• 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 Outcomes (8)

• Percentage of Participants with Prostate Specific Antigen (PSA) Response

  Up to 2 years and 4 months

• Overall Response Rate (ORR)

  Up to 2 years and 4 months

• Maximum Observed Serum Concentration/Radioactivity (Cmax) of JNJ-69086420

  Up to 2 years and 4 months

• Time to Reach Maximum Observed Serum Concentration/Radioactivity (Tmax) 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

  Up to 2 years and 4 months

Study Arms (4)

Part 1: Dose Escalation

EXPERIMENTAL

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

Part 2: Dose Expansion

EXPERIMENTAL

Participants in one or more cohorts will receive JNJ-69086420 at the RP2D(s) determined in Part 1.

Drug: JNJ-69086420

Part 3: Combination Therapy

EXPERIMENTAL

Participants will receive JNJ-69086420 at the determined RP2D(s) and fixed dose of JNJ-78278343.

Drug: JNJ-69086420; Drug: JNJ-78278343

Part 4: HSPC Expansion

EXPERIMENTAL

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; Radiation: Stereotactic body radiation therapy

Interventions

JNJ-69086420 DRUG

Participants will receive JNJ-69086420.

Also known as: Actinium-225-DOTA-h11B6

Part 1: Dose Escalation; Part 2: Dose Expansion; Part 3: Combination Therapy; Part 4: HSPC Expansion

JNJ-78278343 DRUG

Participants will receive JNJ-78278343.

Part 3: Combination Therapy

Stereotactic body radiation therapy RADIATION

Participants will receive stereotactic body radiaition therapy.

Part 4: HSPC Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (11)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

Tulane University Hospital & Clinics

New Orleans, Louisiana, 70112, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

XCancer Omaha / Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 41531507 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: November 25, 2020
• Study Start: November 12, 2020
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (11)