Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Prostate cancer (PC) remains a significant health challenge, particularly in its metastatic castration-resistant form.
• Targeting specific biomarkers like human kallikrein 2 (KLK2) offers a promising avenue for novel PC therapies.

Purpose of the Study:

• To evaluate the safety and determine the recommended phase II dose (RP2D) of pasritamig, a bispecific antibody targeting KLK2 in PC.
• To preliminarily assess the antitumor activity of pasritamig in patients with metastatic castration-resistant PC.

Main Methods:

• A phase I dose-escalation trial was conducted in 174 participants with metastatic castration-resistant PC and prior therapy.
• Pasritamig was administered subcutaneously and intravenously, with dose escalation and varied dosing frequencies to establish safety and RP2D.
• Safety assessments included treatment-related adverse events (TRAEs), while antitumor activity was evaluated by radiographic progression-free survival and prostate-specific antigen (PSA) decrease.

Main Results:

• The RP2D was established as 3.5 mg (day 1), 18 mg (day 8), 300 mg (day 15), and then 300 mg IV every 6 weeks.
• TRAEs occurred in 82.8% of participants, with low rates of grade ≥3 events (9.8%) and grade 1-2 cytokine release syndrome (CRS; 8.9%).
• In the RP2D efficacy population, median radiographic progression-free survival was 7.85 months, and 42.4% achieved a ≥50% PSA decrease.

Conclusions:

• Pasritamig demonstrated a favorable safety profile, manageable TRAEs, and low CRS rates, supporting outpatient administration.
• Preliminary antitumor activity supports KLK2 as a viable target in prostate cancer.
• Pasritamig warrants further clinical development for patients with metastatic castration-resistant PC.