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

Author(s): Mark N. Stein, MD [email protected]¹; Armelle Vinceneux, MD²; Debbie Robbrecht, MD, PhD³; Bernard Doger, MD, PhD⁴; Karen A. Autio, MD⁵; Michael T. Schweizer, MD⁶; Emiliano Calvo, MD, PhD X⁷; Laura Medina, MD⁸; Marloes Van Dongen, MD, PhD⁹; Jean-Laurent Deville, MD¹⁰; Alice Bernard-Tessier, MD¹¹; Debopriya Ghosh, PhD¹²; Kristin Shotts, PhD X¹³; Fei Shen, PhD¹³; Pharavee Jaiprasart, PhD¹³; Ruchi Chaudhary, PhD¹³; Shujian Wu, MD, PhD¹⁴; Leanne Cartee, PhD¹⁴; Robert Schnepp, MD, PhD¹³; Daria Gaut, MD¹⁵; Josh Lauring, MD, PhD X¹³; Sherry C. Wang, PhD¹⁶; Victor M. Villalobos, MD, PhD X¹³; Capucine Baldini, MD¹⁷;

Source: doi.org/10.1200/JCO-25-00678

Dr. Maen Hussein's Thoughts

Pasritamig was administered to patients who had received a median of four prior lines of systemic therapy. It was well tolerated, with manageable adverse events, making it suitable for outpatient administration. The treatment showed a median radiographic progression-free survival of 7.85 months, and 14 out of 33 participants achieved a ≥50% reduction in baseline PSA levels. So, stay tuned.

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.

Author Affiliations

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

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