2. Academic Validation
  3. AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity against Prostate Cancer

AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity against Prostate Cancer

  • Cancer Discov. 2024 Jan 12;14(1):90-103. doi: 10.1158/2159-8290.CD-23-0984.
Olivier Nolan-Stevaux 1,  Cong Li 1,  Lingming Liang 1,  Jinghui Zhan 2,  Juan Estrada 2,  Tao Osgood 2,  Fei Li 3,  Hanzhi Zhang 3,  Ryan Case 4,  Christopher M Murawsky 5,  Bram Estes 6,  Gregory L Moore 7,  Matthew J Bernett 7,  Umesh Muchhal 7,  John R Desjarlais 7,  Binnaz K Staley 1,  Jennitte Stevens 6,  Keegan S Cooke 2,  Famke Aeffner 8,  Oliver Thomas 9,  Julia Stieglmaier 10,  Jae-Lyun Lee 11,  Angela Coxon 2,  Julie M Bailis 1
Affiliations

Affiliations

  • 1 Oncology Research, Amgen Research, Amgen Inc., South San Francisco, California.
  • 2 Oncology Research, Amgen Research, Amgen Inc., Thousand Oaks, California.
  • 3 Structural Biology, Amgen Research, Amgen Inc., South San Francisco, California.
  • 4 Lead Discovery and Characterization, Amgen Research, Amgen Inc., South San Francisco, California.
  • 5 Therapeutic Discovery, Amgen Research, Amgen Inc., Burnaby, Canada.
  • 6 Therapeutic Discovery, Amgen Research, Thousand Oaks, California.
  • 7 Xencor, Inc., Pasadena, California.
  • 8 Translational Safety and Bioanalytical Sciences, Amgen Research, Amgen Inc., South San Francisco, California.
  • 9 Translational Safety and Bioanalytical Sciences, Amgen Research (Munich) GmbH, Munich, Germany.
  • 10 Early Development Oncology, Amgen Research (Munich) GmbH, Munich, Germany.
  • 11 Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
PMID: 37861452 DOI: 10.1158/2159-8290.CD-23-0984
Abstract

The tumor-associated antigen STEAP1 is a potential therapeutic target that is expressed in most prostate tumors and at increased levels in metastatic castration-resistant prostate Cancer (mCRPC). We developed a STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), that is designed to redirect T cells to kill prostate Cancer cells that express STEAP1. AMG 509 mediates potent T cell-dependent cytotoxicity of prostate Cancer cell lines in vitro and promotes tumor regression in xenograft and syngeneic mouse models of prostate Cancer in vivo. The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a patient with mCRPC who achieved an objective response on AMG 509 treatment.

Significance: Immunotherapy in prostate Cancer has met with limited success due to the immunosuppressive microenvironment and lack of tumor-specific targets. AMG 509 provides a targeted immunotherapy approach to engage a patient's T cells to kill STEAP1-expressing tumor cells and represents a new treatment option for mCRPC and potentially more broadly for prostate Cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Kelly et al., p. 76. This article is featured in Selected Articles from This Issue, p. 5.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P990688
    ≥99%, T-cell Activator
    CD3