近日，中国医学科学院王杰及其课题组报道了TROP-2靶向抗体-药物偶联物SHR-A1921治疗晚期或转移性实体瘤。2025年10月23日出版的《癌细胞》杂志发表了这项成果。

该研究是一项首次在人体内进行的三期1期试验（NCT05154604），旨在评估391例预先治疗的晚期/转移性实体瘤患者的TROP-2靶向抗体-药物偶联物SHR-A1921 （1.5-6.0 mg/kg/3周）。132例患者（33.8%）发生≥3级治疗相关不良事件，最常见的是口腔炎，57例患者（14.6%）。SHR-A1921的血液学毒性发生率较低，只有3.1%的患者出现中性粒细胞计数≥3级下降。总体客观缓解率为24.8%(95%可信区间[CI]， 20.6-29.4)，在铂耐药卵巢癌、三阴性乳腺癌、小细胞肺癌、非小细胞肺癌、激素受体阳性乳腺癌、宫颈癌和胆道癌的队列中，总体客观缓解率为18.2%-43.1%。TROP-2表达与治疗效果无显著相关性。总之，SHR-A1921表现出有希望的抗肿瘤活性和可管理的安全性，每3周3.0mg/kg被选择用于进一步的临床开发。

附：英文原文

Title: TROP-2-targeted antibody-drug conjugate SHR-A1921 for advanced or metastatic solid tumors: A first-in-human phase 1 study

Author: Jia Zhong, Lin Wu, Zhengbo Song, Nianzeng Xing, Jiujie Cui, Xingya Li, Kailun Fei, Dihong Tang, Qi Dang, Liang Chen, Tianshu Liu, Caigang Liu, Yong Li, Shichuan Zhang, Xinghua Han, Juxiang Xiao, Feng Guo, Min Yan, Huiting Xu, Chunxiu Yuan, Jincai Zhong, Rongrui Liu, Xiujuan Qu, Shikai Wu, Shusuan Jiang, Yan Yang, Panpan Zhang, Hongqian Guo, Ce Wang, Qiushi Xie, Zhifei Lin, Shuni Wang, Jie Wang

Issue&Volume: 2025-10-23

Abstract: This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5–6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6–29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.

DOI: 10.1016/j.ccell.2025.09.012

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00404-0