A Study of Pasritamig Versus Placebo in Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) (KLK2-comPAS)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Castration-resistant Prostate Neoplasms

Treatments: Biological: Pasritamig; Other: Placebo; Drug: Best Supportive Care (BSC)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07164443

2025-520927-26-00 (Registry Identifier)

78278343PCR3001 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the overall survival (length of time from the start of study to date of death from any cause) for pasritamig (JNJ-78278343) in combination with best supportive care (BSC) as compared to placebo with BSC in participants with metastatic castration-resistant prostate cancer (mCRPC; a stage of cancer that has spread beyond the prostate gland and is no longer responding to hormone therapies).

Enrollment: 663 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Histologically confirmed adenocarcinoma of the prostate
• Metastatic castration-resistant prostate cancer (mCRPC): Disease that is metastatic either to bone, any lymph node, or both without clear evidence of metastasis to visceral organs at the time of screening
• PSA greater than or equal to (>=) 2 nanogram per milliliter (ng/mL) at screening
• In the opinion of the investigator, the next best treatment option is a clinical trial
• Participants should have had all life-prolonging therapies for which they are clinically eligible in the opinion of the investigator and to which they have access. Prior therapies could have been given in any disease setting (not limited to mCRPC). In particular, prior treatment specifications include receipt of the following:

Androgen-receptor pathway inhibitor (ARPI): Must have progressed on at least 1 ARPI and unlikely to benefit from retreatment with another ARPI

Taxanes: Should have received at least 2 previous taxane-based regimens. If a participant has received only 1 taxane regimen, the participant is eligible if:

1. Cabazitaxel is not available
2. The participant's physician deems the participant unsuitable to receive a second taxane regimen due to toxicity risk or prior intolerance Note: a taxane-based regimen consists of at least 2 cycles of a taxane (either as a single agent or in combination with other therapies) administered within the same 2-month period.

Radioligand therapy: Should have been previously treated with at least 1 dose of Prostate-specific membrane antigen (PSMA)-targeted lutetium radioligand therapy (eg, lutetium Lu-177 vipivotide tetraxetan), unless one of the following applies:

1. PSMA-targeted lutetium radioligand therapy is unavailable, not accessible, or not clinically indicated.
2. The participant's physician deems the participant unsuitable to receive PSMA-targeted lutetium radioligand therapy.

Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi): Should have been previously treated with PARPi, if the participant has a known germline or somatic BRCA mutation and treatment is available

• Prior orchiectomy or medical castration (receiving ongoing ADT with a GnRH analog [agonist or antagonist]) prior to the first dose of study treatment and must continue this therapy throughout the treatment phase
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Participants are eligible if they have the following values:

A) eGFR >= 30 milliliters per minute (mL/min) B) Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) less than or equal to (<=) 5 times the Upper Limit of Normal (ULN) C) Serum total bilirubin <= 3 * ULN D) Absolute neutrophil count (ANC) >= 1.0 *10^9/per liter (L) E) Hemoglobin >= 8.0 grams per deciliter (g/dL) F) Platelet count >= 75 * 109/L

Exclusion Criteria

• Venous thromboembolic events within 1 month prior to the first dose of study treatment; uncomplicated (Grade <= 2) deep vein thrombosis is not exclusionary
• Active autoimmune disease within the past 12 months that requires systemic immunosuppressive medications (eg, chronic corticosteroid, methotrexate, or tacrolimus)
• Clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use (>2 liters per minute (L/min) by nasal cannula) to maintain adequate oxygenation
• Prior or concurrent second malignancy (other than the disease under study) for which natural history or treatment could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s)
• Any of the following within 6 months prior to first dose of study treatment:

A) Myocardial infarction B) Severe or unstable angina C) Clinically significant ventricular arrhythmias D) Congestive heart failure (New York Heart Association class II to IV) E) Transient ischemic attack F) Cerebrovascular accident

- Prior treatment with any CD3-directed therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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663 participants in 2 patient groups, including a placebo group

Pasritamig Plus Best Supportive Care (BSC)

Experimental group

Description:

Participants will receive the step-up doses of pasritamig intravenously (IV) on Cycle 1 Day 1 (C1D1) and C1D8, and target dose of pasritamig IV on C1D15 (Cycle 1 duration is 8 weeks). From C2D1 onwards ( Cycle Duration is 6 week), participants will receive pasritamig target dose IV every 6 weeks. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.

Treatment:

Drug: Best Supportive Care (BSC)

Biological: Pasritamig

Placebo Plus BSC

Placebo Comparator group

Description:

Participants will receive the step-up doses of placebo IV on C1D1 and C1D8, and target dose of placebo on C1D15. From C2D1 onwards, participants will receive placebo target dose IV every 6 weeks and will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC at the discretion of the physician.

Treatment:

Drug: Best Supportive Care (BSC)

Other: Placebo