Multiple classes of therapies targeting claudin-18 isoform 2 (CLDN18.2) are under development for the treatment of advanced gastroesophageal adenocarcinoma and other solid tumors. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the final results of the phase 3 SPOTLIGHT trial were presented, demonstrating a significant survival benefit from the addition of the CLDN18.2-specific antibody zolbetuximab to chemotherapy in the first-line treatment of advanced gastroesophageal adenocarcinomas with ≥ 75% CLDN18.2 expression. Early-phase trial results presented at ASCO 2024 showed promising efficacy and safety of the afucosylated CLDN18.2-specific antibody FG-M108 in combination with chemotherapy in the first-line treatment of CLDN18.2-positive advanced gastroesophageal and pancreatic cancers. In addition, several early-phase trials presented at ASCO 2024 investigate other CLDN18.2-targeting approaches in CLDN18.2-positive refractory advanced solid tumors, including the CLDN18.2-targeting antibody–drug conjugates LM-302 and IBI343, the bispecific anti-CLDN18.2/CD3 antibody IBI38, and the chimeric antigen receptor T cell therapy satricabtagene autoleucel. These novel approaches could potentially expand the benefit of CLDN18.2-targeting therapies to a broader range of tumor types and to tumors expressing lower levels of CLDN18.2.

中文翻译：

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针对 Claudin-18.2 进行癌症治疗：2024 年 ASCO 年会更新


多种针对claudin-18亚型2 (CLDN18.2)的疗法正在开发中，用于治疗晚期胃食管腺癌和其他实体瘤。在2024年美国临床肿瘤学会（ASCO）年会上，公布了3期SPOTLIGHT试验的最终结果，证明一线化疗中添加CLDN18.2特异性抗体zolbetuximab可带来显着的生存获益治疗 CLDN18.2 表达≥ 75% 的晚期胃食管腺癌。 ASCO 2024 上公布的早期试验结果显示，无岩藻糖基化 CLDN18.2 特异性抗体 FG-M108 联合化疗在 CLDN18.2 阳性晚期胃食管癌和胰腺癌的一线治疗中具有良好的疗效和安全性。此外，在 ASCO 2024 上提出的几项早期试验研究了 CLDN18.2 阳性难治性晚期实体瘤的其他 CLDN18.2 靶向方法，包括 CLDN18.2 靶向抗体-药物缀合物 LM-302 和 IBI343（双特异性抗体）抗CLDN18.2/CD3抗体IBI38，以及嵌合抗原受体T细胞疗法satricabtagene autoleucel。这些新方法可能会将 CLDN18.2 靶向疗法的益处扩大到更广泛的肿瘤类型和表达较低水平 CLDN18.2 的肿瘤。