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, Yueyin Pan, Ying Cheng, Sheng Hu, Jin Wang, Mengyue Shi, Ke Wang, Han Hu, Lin Shen
{"title":"Tislelizumab 用于既往接受过治疗的局部晚期不可切除/转移性微卫星不稳定性高/错配修复缺陷实体瘤。","authors":"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, Yueyin Pan, Ying Cheng, Sheng Hu, Jin Wang, Mengyue Shi, Ke Wang, Han Hu, Lin Shen","doi":"10.21147/j.issn.1000-9604.2024.03.03","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 <i>vs.</i> 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 follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.</p><p><strong>Conclusions: </strong>Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.0000,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230881/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors.\",\"authors\":\"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, Yueyin Pan, Ying Cheng, Sheng Hu, Jin Wang, Mengyue Shi, Ke Wang, Han Hu, Lin Shen\",\"doi\":\"10.21147/j.issn.1000-9604.2024.03.03\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 <i>vs.</i> 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 follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.</p><p><strong>Conclusions: </strong>Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.</p>\",\"PeriodicalId\":9882,\"journal\":{\"name\":\"Chinese Journal of Cancer Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2024-06-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230881/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Journal of Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21147/j.issn.1000-9604.2024.03.03\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2024.03.03","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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 follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.
Conclusions: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
期刊介绍：
Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013.
CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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