Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

作者：Jian Li, Ye Xu, Aimin Zang, Yunong Gao, Quanli Gao, Yanqiao Zhang, Dong Wang, Jianming Xu, Ying Yuan, Haiping Jiang, Jieer Ying, Chunmei Shi, Yanhong Deng, Jing Wang, Tianshu Liu, Yi Huang, Xiaoping Qian, Yue-Yin Pan, Ying Cheng, Sheng Hu, Jin Wang, Mengyue Shi, Ke Wang, Han Hu, Lin Shen · 发表于：Chinese Journal of Cancer Research · 年份：2024 · DOI：10.21147/j.issn.1000-9604.2024.03.03 · 被引用次数：19 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Lung Cancer Treatments and Mutations

Objective The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors. Methods Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1). Results Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1−58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1–54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2−86.3); others (n=20): 60.0% (95% CI, 36.1−80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median fol...