Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study

  • Cancer Discov. 2024 Jan 12;14(1):76-89. doi: 10.1158/2159-8290.CD-23-0964.
William K Kelly  #  1  2 ,  Daniel C Danila  #  3  4 ,  Chia-Chi Lin  5 ,  Jae-Lyun Lee  6 ,  Nobuaki Matsubara  7 ,  Patrick J Ward  2  8 ,  Andrew J Armstrong  9 ,  David Pook  10 ,  Miso Kim  11 ,  Tanya B Dorff  12 ,  Stefanie Fischer  13 ,  Yung-Chang Lin  14 ,  Lisa G Horvath  15 ,  Christopher Sumey  16 ,  Zhao Yang  17 ,  Gabor Jurida  17 ,  Kristen M Smith  18 ,  Jamie N Connarn  18 ,  Hweixian L Penny  17 ,  Julia Stieglmaier  19 ,  Leonard J Appleman  20
Affiliations
  • 1. Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania.
  • 2. Sarah Cannon Research Institute, Nashville, Tennessee.
  • 3. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • 4. Department of Medicine, Weill Cornell Medical College, New York, New York.
  • 5. National Taiwan University Hospital, Taipei, Taiwan.
  • 6. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • 7. National Cancer Center Hospital East, Chiba, Japan.
  • 8. Oncology Hematology Care, Cincinnati, Ohio.
  • 9. Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina.
  • 10. Monash Health, Clayton, Victoria, Australia.
  • 11. Seoul National University Hospital, Seoul, South Korea.
  • 12. City of Hope, Duarte, California.
  • 13. Department of Medical Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
  • 14. Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • 15. Chris O'Brien Lifehouse, University of Sydney, Sydney, New South Wales, Australia.
  • 16. Sanford Cancer Center, Sioux Falls, South Dakota.
  • 17. Amgen Inc., Thousand Oaks, California.
  • 18. Amgen Inc., South San Francisco, California.
  • 19. Amgen Research (Munich) GmbH, Munich, Germany.
  • 20. UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
  • # Contributed equally.
PMID: 37861461 DOI: 10.1158/2159-8290.CD-23-0964
Abstract

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.

Significance: 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. See related commentary by Hage Chehade et al., p. 20. See related article by Nolan-Stevaux et al., p. 90. This article is featured in Selected Articles from This Issue, p. 5.

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