Amgen Xaluritamig (AMG509) is a six-transmembrane epithelial antigen-targeted T cell engager for prostate 1 (STEAP1) designed to facilitate lysis of STEAP1-expressing cancer cells, such as advanced cancer cells. In Cancer Discovery**, the investigators stated that the preliminary efficacy results of Xaluritamig were numerically higher than those reported for other T cells involved in prostate cancer.
This first-in-human study reported monotherapy dose-finding in patients with metastatic castration-tolerant cancer (MCRPC), primarily taxane pretreatment. Ninety-seven patients received 1 intravenous injection with a dose range of 0001 to 20 mg weekly or every 2 weeks. The MTD was determined to be administered intravenously via a 3-step dose of 15 mg。The most common** related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). The levels of IFN, IL2, IL6, and TNF were measured centrally using a multiplex ECL (electrochemiluminescence immunoassay technique) assay (10-factor V-plex, MESO Scale Discovery). CRS occurs predominantly in Cycle 1 and improves with premedication and gradual dosing. 
Prostate-specific antigen (PSA) and RECIST responses were encouraging in all cohorts [49% PSA50; 24% objective effective rate (ORR) at the target dose of 0There was a higher frequency at 75 mg (59% PSA50; 41% ORR). 
To assess immunogenicity, ADA formation is measured at baseline and before each dose of C1, and then every 2 weeks until the end of **. Conjugated antibodies were evaluated with a bridging immunoassay based on MSD electrochemiluminescence ECL detection, and neutralizing antibodies were evaluated with a cell-based bioassay. Xaluritamig is a novel form of immunology for prostate cancer that has shown encouraging results to support further development. Compared to historically established methods for patients with advanced MCRPC**, Xaluritamig showed an encouraging response (PSA and RECIST). This study provides a proof of concept for the T cell receptor as a potential approach for prostate cancer, validates the role of Steap1 as a target, and supports further clinical studies of xaluritamig in prostate cancer.