Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.
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, FranceRelated Articles
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