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

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 1

Conditions: Prostatic Neoplasms; Adenocarcinoma

Treatments: Drug: JNJ-69086420; Radiation: Stereotactic body radiation therapy; Drug: JNJ-78278343

Study type: Interventional

Funder types: Industry

Identifiers

NCT04644770

69086420PCR1001 (Other Identifier)

CR108817

Details and patient eligibility

About

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.

Enrollment: 247 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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247 participants in 4 patient groups

Part 1: Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: JNJ-69086420

Part 2: Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: JNJ-69086420

Part 3: Combination Therapy

Experimental group

Description:

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

Treatment:

Drug: JNJ-78278343

Drug: JNJ-69086420

Part 4: HSPC Expansion

Experimental group

Description:

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).

Treatment:

Radiation: Stereotactic body radiation therapy

Drug: JNJ-69086420