2. Academic Validation
  3. Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study

Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study

  • J Clin Oncol. 2025 Aug;43(22):2515-2526. doi: 10.1200/JCO-25-00678.
Mark N Stein 1,  Armelle Vinceneux 2,  Debbie Robbrecht 3,  Bernard Doger 4,  Karen A Autio 5,  Michael T Schweizer 6,  Emiliano Calvo 7,  Laura Medina 8,  Marloes Van Dongen 9,  Jean-Laurent Deville 10,  Alice Bernard-Tessier 11,  Debopriya Ghosh 12,  Kristin Shotts 13,  Fei Shen 13,  Pharavee Jaiprasart 13,  Ruchi Chaudhary 13,  Shujian Wu 14,  Leanne Cartee 14,  Robert Schnepp 13,  Daria Gaut 15,  Josh Lauring 13,  Sherry C Wang 16,  Victor M Villalobos 13,  Capucine Baldini 17
Affiliations

Affiliations

  • 1 Columbia University Medical Center, New York, NY.
  • 2 Centre Léon Bérard, Lyon, France.
  • 3 Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • 4 START Madrid-FJD, Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain.
  • 5 Memorial Sloan Kettering Cancer Center, New York, NY.
  • 6 Fred Hutchinson Cancer Center, University of Washington, Seattle, WA.
  • 7 START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain.
  • 8 Servicio de Oncología Médica, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
  • 9 Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • 10 AP-HM Hôpital de la Timone, Marseille, France.
  • 11 Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.
  • 12 Johnson & Johnson, Raritan, NJ.
  • 13 Johnson & Johnson, Spring House, PA.
  • 14 Johnson & Johnson, Horsham, PA.
  • 15 Johnson & Johnson, Los Angeles, CA.
  • 16 Johnson & Johnson, San Francisco, CA.
  • 17 Drug Development Department (DITEP), Institut Gustave Roussy, Villejuif, France.
PMID: 40450573 DOI: 10.1200/JCO-25-00678
Abstract

Purpose: We report phase I trial results for pasritamig, a first-in-class, T-cell-engaging bispecific antibody targeting human Kallikrein 2 (KLK2) expressed on the surface of prostate Cancer (PC) cells.

Methods: Participants had metastatic castration-resistant PC and ≥1 prior therapy. Pasritamig was escalated from 0.5 mg to 2,000 mg for subcutaneous administration and from 150 mg to 900 mg for intravenous (IV) administration at dosing frequencies ranging from once every week to once every 6 weeks with different step-up dosing schedules. The primary objectives were to determine safety and the recommended phase II dose (RP2D) of pasritamig. Secondary objectives included preliminary assessment of antitumor activity.

Results: One hundred seventy-four participants received pasritamig, with a median of 4 prior lines of systemic therapy. Treatment-related adverse events (TRAEs) occurred in 144 of 174 (82.8%) participants, with 17 of 174 (9.8%) experiencing grade ≥3 TRAEs. The RP2D was determined to be 3.5 mg (day 1), 18 mg (day 8), 300 mg (day 15), and then 300 mg IV once every 6 weeks. In the RP2D safety population (n = 45), infusion-related reactions (11/45, 24.4%), fatigue (7/45, 15.6%), cytokine release syndrome (CRS; 4/45, 8.9%, all grade 1), and Lipase increase (4/45, 8.9%) were the most frequent TRAEs; all were grade 1 or 2. In the RP2D efficacy population (n = 33), median radiographic progression-free survival was 7.85 (95% CI, 2.89 to not estimable) months, and 14 of 33 (42.4%) participants achieved a ≥50% decrease from baseline in prostate-specific antigen.

Conclusion: Pasritamig demonstrated a favorable safety profile with very low rates of CRS and could be safely administered in an outpatient setting. Preliminary antitumor activity demonstrated proof of concept for KLK2 as a target in PC, warranting further development of pasritamig.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P991015
    99.031%, KLK2-CD3R Binder
    CD3