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

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-06-30 DOI:10.21147/j.issn.1000-9604.2024.03.03
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 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}
引用次数: 0

Abstract

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.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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。
研究目的开放标签的II期RATIONALE-209研究评估了tislelizumab(抗程序性细胞死亡蛋白1抗体)作为微卫星不稳定性高(MSI-H)/错配修复缺陷(dMMR)肿瘤的组织诊断单药疗法:方法:研究人员招募了曾接受过治疗、局部晚期不可切除或转移性MSI-H/dMMR实体瘤的成人患者。患者每3周接受一次200毫克的tislelizumab静脉注射。客观反应率(ORR;主要终点)、反应持续时间(DoR)和无进展生存期(PFS)由独立审查委员会(实体瘤反应评估标准 v1.1)进行评估:80名患者入组并接受了治疗;75名患者(93.8%)在基线时患有可测量的疾病。大多数患者患有转移性疾病,并且之前至少接受过一次晚期/转移性疾病治疗(79 例;98.8%)。在主要分析中(数据截止日期为 2021 年 7 月 8 日;中位随访 15.2 个月),总体 ORR [46.7%;95% 置信区间 (95%CI),35.1-58.6;单侧 Pvs.预设历史对照 ORR 为 10%;5 名(6.7%)患者完全应答。长期随访未达到中位DoR、PFS和总生存期(数据截止日期为2022年12月5日;中位随访28.9个月)。Tislelizumab的耐受性良好,没有出现意外的安全信号。53.8%的患者发生了≥3级的治疗相关不良事件(TRAEs);7.5%的患者因TRAEs而中断治疗:结论:Tislelizumab可显著改善既往接受过治疗的局部晚期不可切除或转移性MSI-H/dMMR肿瘤患者的ORR,且耐受性普遍良好。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
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.
期刊最新文献
Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China. Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. Potential value of detection of minimal residual disease in colorectal cancer following radical resection. Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma. SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1