Document Type
Article
Publication Date
10-20-2023
Abstract
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.
Recommended Citation
Kelly, William K.; Danila, Daniel C.; Lin, Chia-Chi; Lee, Jae-Lyun; Matsubara, Nobuaki; Ward, Patrick J.; Armstrong, Andrew J.; Pook, David; Kim, Miso; Dorff, Tanya B.; Fischer, Stefanie; Lin, Yung-Chang; Horvath, Lisa G.; Sumey, Christopher; Yang, Zhao; Jurida, Gabor; Smith, Kristen M.; Connarn, Jamie N.; Penny, Hweixian L.; Stieglmaier, Julia; and Appleman, Leonard J., "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" (2023). Kimmel Cancer Center Faculty Papers. Paper 115.
https://jdc.jefferson.edu/kimmelccfp/115
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Supplemental Materials
PubMed ID
37861461
Language
English
Comments
This article is the author's final published version in Cancer Discovery, Volume 14, Issue 1, 12 January 2024, Pg. 76 - 89.
The published version is available at https://doi.org/10.1158/2159-8290.cd-23-0964. Copyright © 2023 The Authors; Published by the American Association for Cancer Research.