Testing Pasritamig Before Surgery for the Treatment of Localized Prostate Cancer

Inclusion Criteria:

• Must be willing to provide informed consent prior to any study specific procedures.

• Age ≥ 18 years.

• Documented histologically confirmed adenocarcinoma of the prostate:

  • Unfavourable intermediate risk:

    --- Grade Group 1 with PSA 10-20 ng/mL, T2b-T2c OR Grade Group 2 with PSA 10-20 ng/mL, T2b-T2c, and/or ≥50% biopsy cores positive OR Grade Group 3 with PSA <20 ng/mL.

  • High-risk localized prostate cancer with no very-high-risk features and exactly one high-risk feature:

    • T3a OR
    • Grade Group 4 or 5 OR
    • PSA > 20 ng/dL

  • Very high-risk localized prostate cancer. At least one of the following:

    • T3b-T4
    • Primary Gleason pattern 5
    • 2 or 3 high-risk features
    • >4 cores with Grade Group 4 or 5

• Negative for distant metastases on conventional (i.e. CT bone scan) and PSMA PET imaging within 60 days of enrollment. Patients with evidence of non-measurable (i.e. per RECIST v1.1) metastatic lymphadenopathy as detected by PSMA PET will be eligible if ≤3 radiation isocenters are detectable.

• Eastern cooperative oncology group performance (ECOG) status 0-1.

• Eligible and planned for radical prostatectomy.

• Must have adequate archival biopsy tissue available for KLK2 assessment.

• Participants who are sexually active with a partner of childbearing potential or a pregnant partner must agree to use contraception, including a condom, during study treatment and for at least 6 months after the last dose of pasritamig. Participants must also agree not to donate sperm during study treatment and for at least 6 months after the last dose of pasritamig.

• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

  • Hemoglobin ≥ 9 g/dL with no blood transfusion in the past 28 days

  • Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; however, participants with documented Duffy-null associated neutrophil count or other benign chronic neutropenia may be eligible with ANC ≥1.0 × 10⁹/L if clinically stable and without a history of recurrent or severe infections, at the discretion of the investigator. Platelet count ≥ 100 x 109/L

  • Total bilirubin ≤1.5 × institutional upper limit of normal (ULN), except participants with known or suspected Gilbert syndrome may be eligible with total bilirubin ≤3 × ULN, provided direct bilirubin is ≤1.5 × ULN and there is no clinical evidence of hepatic dysfunction.Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN

  • Patients must have creatinine clearance estimated of ≥30 mL/min:

    • Estimated creatinine clearance = (140-age [years]) x weight (kg) / serum creatinine (mg/dL) x 72

Exclusion Criteria:

• Subjects with small cell or neuroendocrine prostate cancer.

• Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study treatment. Prophylactic anti-infective agents are allowed.

• Solid organ or bone marrow transplantation.

• Suspected or known allergies, hypersensitivity, or intolerance to excipients of pasritamig (refer to the latest IB for pasritamig).

• Received immunosuppressive doses of systemic medications, such as glucocorticoids (doses >10 mg/day prednisone or equivalent) within 3 days prior to the first dose of study treatment. A single course of glucocorticoids is permitted as prophylaxis for imaging contrast (i.e., for participants with allergies to contrast). If glucocorticoids were used to treat immune-related adverse events associated with prior therapy, ≥7 days must have elapsed since the last dose of corticosteroid.

• Received or plans to receive any live, attenuated vaccine within 4 weeks before the first dose of study treatment. Live, attenuated influenza vaccines are permitted as late as 7 days before the study treatment.

• Distant metastasis based on conventional imaging (clinical stage M1) and PSMA PET within 60 days of enrollment. Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Participants are considered eligible only if the central radiological review confirms clinical stage M0. As noted above, non-measurable nodal metastases detected on PSMA PET will be allowed to enroll if radiation isocenters are detectable.

• cT4 disease (tumor is fixed or invades adjacent structures other than seminal vesicles) is excluded.

• Prior androgen deprivation therapy or other systemic treatment for prostate cancer.

• Prior treatment with KLK2-targeted therapy and/or with any CD3-directed therapy

• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. This includes, but not limited to, the following:

  • Patients with positive HIV titers or active hepatitis (i.e., Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
  • Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.
  • Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.

• Any of the following within 6 months prior to first dose of study treatment:

  • Myocardial infarction,
  • Severe or unstable angina,
  • Clinically significant ventricular arrhythmias,
  • Congestive heart failure (New York Heart Association class II to IV),
  • Transient ischemic attack,
  • Cerebrovascular accident

• Active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications (e.g., chronic corticosteroid, methotrexate, or tacrolimus).