Safety and efficacy of acapatamab, a prostate-specific membrane antigen (PSMA) x CD3 bispecific T-cell engager were evaluated in a first-in-human study in metastatic castration-resistant prostate cancer (mCRPC).
Patients with mCRPC refractory to androgen receptor pathway inhibitor therapy and taxane-based chemotherapy received target acapatamab doses ranging from 0.003 mg-0.9 mg in dose exploration (7 dose levels) and 0.3 mg (recommended phase 2 dose) in dose expansion intravenously Q2W. Safety (primary objective), pharmacokinetics, and antitumor activity (secondary objectives) were assessed.
In all, 133 patients (dose exploration, n=77; dose expansion, n=56) received acapatamab. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event seen in 97.4% and 98.2% of patients in dose exploration and dose expansion respectively; grade ≥ 3 was seen in 23.4% and 16.1%, respectively. Most CRS events were seen in treatment cycle 1; incidence and severity decreased at/beyond cycle 2. In dose expansion, confirmed prostate-specific antigen responses (PSA50) were seen in 30.4% of patients and radiographic partial responses in 7.4% (RECIST 1.1). Median PSA progression-free survival (PFS) was 3.3 months (95% CI, 3.0-4.9), radiographic PFS per PCWG3 was 3.7 months (95% CI, 2.0-5.4). Acapatamab induced T-cell activation and increased cytokine production several-fold within 24h of initiation. Treatment-emergent antidrug antibodies were detected in 55% and impacted serum exposures in 36% of patients in dose expansion.
Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed. Acapatamab demonstrated pharmacokinetic and pharmacodynamic activity.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2024 Feb 01 [Epub ahead of print]
Tanya Dorff, Lisa G Horvath, Karen Autio, Alice Bernard-Tessier, Matthew B Rettig, Jean-Pascal Machiels, Mehmet A Bilen, Martijn P Lolkema, Nabil Adra, Sylvie Rottey, Richard Greil, Nobuaki Matsubara, Daniel S W Tan, Alvin Wong, Hiroji Uemura, Charlotte Lemech, Johannes Meran, Youfei Yu, Mukul Minocha, Mason McComb, Hweixian Leong Penny, Vinita Gupta, Xuguang Hu, Gabor Jurida, Hosein Kouros-Mehr, Margit M Janát-Amsbury, Tobias Eggert, Ben Tran
City Of Hope National Medical Center, Duarte, CA, United States., Chris O'Brien Lifehouse, Sydney, New South Wales, Australia., Memorial Sloan Kettering Cancer Center, New York, NY, United States., Institut Gustave Roussy, Paris, France., University of California, Los Angeles, Los Angeles, CA, United States., Cancer center, Cliniques universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université catholique de Louvain, Brussels, Belgium, Brussels, Belgium., Emory University Hospital, Atlanta, GA, United States., Amgen (Netherlands), Breda, Netherlands., Indiana University School of Medicine, Indianapolis, IN, United States., Ghent University Hospital - 4B11, Ghent, Belgium., Paracelsus Medical University Salzburg, Salzburg, Salzburg, Austria., National Cancer Center Hospital East, Chiba, Japan., National Cancer Centre Singapore, Singapore, Singapore., National University Cancer Institute, Singapore, Singapore., Yokohama City University Medical Center, Yokohama, Japan., Scientia Clinical Research Ltd, Sydney, NSW, Australia., Hospital Barmherzige Brueder, Vienna, Austria., Amgen Inc., Thousand Oaks, CA, United States., Amgen Inc., Thousand Oaks, United States., Amgen (United States), Thousand Oaks, CA, United States., Peter MacCallum Cancer Centre, Melbourne, Australia.