Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer.
Cancer discovery. 2023 Oct 20 [Epub ahead of print]
William K Kelly, Daniel C Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J Ward, Andrew J Armstrong, David Pook, Miso Kim, Tanya B Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M Smith, Jamie N Connarn, Hweixian L Penny, Julia Stieglmaier, Leonard J Appleman
Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., National Taiwan University Hospital, Taipei, Taiwan., Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., National Cancer Center Hospital East, Chiba, Japan., Sarah Cannon Research Institute, Nashville, Tennessee., Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina., Monash Health, Clayton, Victoria, Australia., Seoul National University Hospital, Seoul, South Korea., City of Hope, Duarte, California., Department of Medical Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan., Chris O'Brien Lifehouse, University of Sydney, Sydney, New South Wales, Australia., Sanford Cancer Center, Sioux Falls, South Dakota., Amgen Inc., Thousand Oaks, California., Amgen Inc., South San Francisco, California., Amgen Research (Munich) GmbH, Munich, Germany., UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.