Xaluritamig (AMG 509) 是一种六跨膜前列腺上皮抗原 1 (STEAP1) 靶向 T 细胞接合剂，旨在促进表达 STEAP1 的癌细胞（例如晚期前列腺癌中的细胞）裂解。这项首次人体研究报告了对转移性去势抵抗性前列腺癌 (mCRPC) 患者的单一疗法剂量探索，主要是紫杉烷预处理。 97 名患者每周或每两周接受 ≥1 次静脉注射剂量，剂量范围为 0.001 至 2.0 mg。 MTD 确定为 1.5 mg i.v.每周一次，分三步服用。最常见的治疗相关不良事件是细胞因子释放综合征（CRS；72%）、疲劳（45%）和肌痛（34%）。 CRS 主要发生在第 1 周期期间，并通过术前用药和分步给药而得到改善。各队列中的前列腺特异性抗原 (PSA) 和 RECIST 反应令人鼓舞 [49% PSA50；49% PSA50] 24% 客观缓解率 (ORR)]，目标剂量≥0.75 mg 时出现频率更高（59% PSA50；41% ORR）。 Xaluritamig 是一种新型前列腺癌免疫疗法，已显示出令人鼓舞的结果，支持进一步发展。与历史上针对晚期 mCRPC 患者的既定治疗方法相比，Xaluritamig 表现出令人鼓舞的反应（PSA 和 RECIST）。这项研究为 T 细胞接合剂作为前列腺癌的潜在治疗方法提供了概念证明，验证了 STEAP1 作为靶点，并支持 xaluritamig 在前列腺癌中的进一步临床研究。©2023由美国癌症研究协会出版。

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.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.©2023 The Authors; Published by the American Association for Cancer Research.