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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.

Publication ,  Journal Article
Kelly, WK; Danila, DC; Lin, C-C; Lee, J-L; Matsubara, N; Ward, PJ; Armstrong, AJ; Pook, D; Kim, M; Dorff, TB; Fischer, S; Lin, Y-C; Sumey, C ...
Published in: Cancer Discov
January 12, 2024

UNLABELLED: 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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Published In

Cancer Discov

DOI

EISSN

2159-8290

Publication Date

January 12, 2024

Volume

14

Issue

1

Start / End Page

76 / 89

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Oxidoreductases
  • Male
  • Immunotherapy
  • Humans
  • Antigens, Neoplasm
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
 

Citation

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Kelly, W. K., Danila, D. C., Lin, C.-C., Lee, J.-L., Matsubara, N., Ward, P. J., … Appleman, L. J. (2024). 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, 14(1), 76–89. https://doi.org/10.1158/2159-8290.CD-23-0964
Kelly, William K., Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, et al. “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 14, no. 1 (January 12, 2024): 76–89. https://doi.org/10.1158/2159-8290.CD-23-0964.
Kelly WK, Danila DC, Lin C-C, Lee J-L, Matsubara N, Ward PJ, et al. 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.
Kelly, William K., et al. “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, vol. 14, no. 1, Jan. 2024, pp. 76–89. Pubmed, doi:10.1158/2159-8290.CD-23-0964.
Kelly WK, Danila DC, Lin C-C, Lee J-L, Matsubara N, Ward PJ, Armstrong AJ, Pook D, Kim M, Dorff TB, Fischer S, Lin Y-C, Horvath LG, Sumey C, Yang Z, Jurida G, Smith KM, Connarn JN, Penny HL, Stieglmaier J, Appleman LJ. 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.

Published In

Cancer Discov

DOI

EISSN

2159-8290

Publication Date

January 12, 2024

Volume

14

Issue

1

Start / End Page

76 / 89

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Prostatic Neoplasms, Castration-Resistant
  • Prostate-Specific Antigen
  • Oxidoreductases
  • Male
  • Immunotherapy
  • Humans
  • Antigens, Neoplasm
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology