Pasritamig (JNJ-78278343), is emerging as a potential new treatment for metastatic castration-resistant prostate cancer. Targeting human kallikrein 2 (KLK2), a protein highly expressed on prostate cancer cells but minimally in healthy tissues, pasritamig simultaneously binds KLK2 and CD3 receptors on T cells to unleash a potent immune attack on tumors.
Early results from a first-in-human phase 1 study (NCT04898634), demonstrate that pasritamig is safe, well-tolerated, and exhibits promising antitumor activity, offering hope for patients with limited options.

The study enrolled 174 men with mCRPC, with a median age of 69 years and a median of four prior therapies, including androgen receptor pathway inhibitors (99.4%), taxane chemotherapy (78.2%), and lutetium-177 vipivotide tetraxetan (17.2%).

Patients received pasritamig via subcutaneous (SC) or intravenous (IV) administration, given weekly to every six weeks, using various step-up dosing schedules to minimize side effects. Dexamethasone pre-medication was required to manage initial doses. The primary goal was to assess safety and determine the recommended phase 2 dose (RP2D), with secondary objectives evaluating preliminary efficacy.

Safety results are encouraging. No pasritamig-related deaths occurred, and only one dose-limiting toxicity (transient grade 3 liver enzyme elevation) was reported at a 50 mg SC dose. Most patients (82.2%) experienced treatment-related adverse events (TRAEs), but these were predominantly mild to moderate (grade 1–2), with only 9.2% experiencing grade 3 or higher TRAEs.

Efficacy data are equally promising. In the RP2D efficacy population (33 patients receiving 300 mg every 6 weeks IV), 42.4% achieved a PSA50 response (a ≥50% decline in prostate-specific antigen levels), a key indicator of tumor control. The median radiographic progression-free survival (rPFS) was 6.77 months, with 39.4% of patients still ongoing. Among 85 patients with measurable disease, the objective response rate (ORR) was 16.1% for those with lymph node and/or bone metastases and 3.7% for those with visceral disease, with a median duration of response of 11.27 months.

Pasritamig’s success validates KLK2 as a novel target for T-cell redirection in mCRPC, addressing an unmet need for targeted immunotherapies.

With phase 3 trials planned, pasritamig could increase the number of mCRPC treatments by offering a safe, effective, and immunologically driven option.

Source.