Publikation

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.

Wissenschaftlicher Artikel/Review - 20.10.2023

Bereiche
PubMed
DOI
Kontakt

Zitation
Kelly W, Danila D, Lin C, Lee J, Matsubara N, Ward P, Armstrong A, Pook D, Kim M, Dorff T, Fischer S, Lin Y, Horvath L, Sumey C, Yang Z, Jurida G, Smith K, Connarn J, Penny H, Stieglmaier J, Appleman L. 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 2023:OF1-OF14.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Cancer Discov 2023
Veröffentlichungsdatum
20.10.2023
eISSN (Online)
2159-8290
Seiten
OF1-OF14
Kurzbeschreibung/Zielsetzung

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.