"Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study"

作者全名："Shi, Yuankai; Qin, Xintian; Peng, Xingchen; Zeng, Aiping; Li, Jingao; Chen, Chuanben; Qiu, Sufang; Pan, Suming; Zheng, Yulong; Cai, Jing; Chen, Xiaopin; Qu, Shenhong; Lin, Lizhu; Huang, Jianli; Wu, Hui; Lu, Ying; Wang, Wei; Hu, Changlu; He, Xia; Yu, Zhonghua; Liu, Xiaojian; Xie, Bo; Liu, Anwen; Hu, Guangyuan; Jing, Shanghua; Zhang, Qingyuan; Guo, Renhua; Li, Qi; Hong, Jinsheng; Jin, Feng; Meng, Juan; Shi, Jianhua; Wang, Peiguo; Cui, Jiuwei; Yang, Kunyu; Zhang, Xuebang; Li, Xiaojiang; Shen, Liangfang; He, Yuxiang; Zhai, Limin; Sun, Xiuhua; Ge, Junyou; Qing, Yan; Zong, Dekang"

作者地址："[Shi, Yuankai] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Med Oncol, Beijing Key Lab Clin Study Anticanc Mol Targeted, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China; [Shi, Yuankai] Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China; [Shi, Yuankai] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China; [Qin, Xintian] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Dept Med Oncol, Guangzhou, Peoples R China; [Peng, Xingchen] Sichuan Univ, West China Hosp, Dept Biotherapy, State Key Lab Biotherapy, Chengdu, Peoples R China; [Peng, Xingchen] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu, Peoples R China; [Zeng, Aiping] Guangxi Med Univ, Guangxi Canc Prevent & Treatment Inst, Dept Resp Oncol, Canc Hosp, Nanning, Peoples R China; [Li, Jingao] Jiangxi Canc Hosp, Dept Head & Neck Radiotherapy, Nanchang, Peoples R China; [Chen, Chuanben; Qiu, Sufang] Fujian Canc Hosp, Dept Oncol Radiotherapy, Fuzhou, Peoples R China; [Pan, Suming] Yue Bei Peoples Hosp, Dept Oncol Radiotherapy, Shaoguan, Peoples R China; [Zheng, Yulong] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Med Oncol, Hangzhou, Peoples R China; [Cai, Jing] Nantong Tumor Hosp, Dept Oncol Radiotherapy, Nantong, Peoples R China; [Chen, Xiaopin] Chongqing Med Univ, Affiliated Hosp 1, Dept Med Oncol, Chongqing, Peoples R China; [Qu, Shenhong] Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Head & Neck Surg, Nanning, Peoples R China; [Lin, Lizhu] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Med Oncol, Guangzhou, Peoples R China; [Huang, Jianli] Fujian Med Univ, Zhangzhou Municipal Hosp Fujian Prov, Zhangzhou Affiliated Hosp, Dept Oncol Radiotherapy, Zhangzhou, Peoples R China; [Wu, Hui] Henan Canc Hosp, Dept Oncol Radiotherapy, Zhengzhou, Peoples R China; [Lu, Ying] Liuzhou Workers Hosp, Dept Med Oncol, Liuzhou, Peoples R China; [Wang, Wei] Hunan Canc Hosp, Dept Med Oncol Gastroenterol & Urol, Changsha, Peoples R China; [Hu, Changlu] Anhui Prov Canc Hosp, Dept Med Oncol, Hefei, Peoples R China; [He, Xia] Jiangsu Canc Hosp, Dept Oncol Radiotherapy, Nanjing, Peoples R China; [Yu, Zhonghua] Guangdong Med Univ, Affiliated Hosp, Dept Med Oncol, Zhanjiang, Peoples R China; [Liu, Xiaojian] Fudan Univ, Canc Hosp, Dept Med Oncol, Shanghai, Peoples R China; [Xie, Bo] Gen Hosp Southern Theatre Command, Dept Med Oncol, Guangzhou, Peoples R China; [Liu, Anwen] Nanchang Univ, Affiliated Hosp 2, Dept Med Oncol, Nanchang, Peoples R China; [Hu, Guangyuan] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Med Oncol, Tongji Med Coll, Wuhan, Peoples R China; [Jing, Shanghua] Hebei Med Univ, Hosp 4, Dept Otolaryngol, Shijiazhuang, Peoples R China; [Zhang, Qingyuan] Harbin Med Univ, Affiliated Canc Hosp, Dept Med Breast Oncol, Harbin, Peoples R China; [Guo, Renhua] Nanjing Med Univ, Affiliated Hosp 1, Jiangsu Prov Hosp, Dept Med Oncol, Nanjing, Peoples R China; [Li, Qi] Shanghai Gen Hosp, Dept Med Oncol, Shanghai, Peoples R China; [Hong, Jinsheng] Fujian Med Univ, Affiliated Hosp 1, Dept Oncol Radiotherapy, Fuzhou, Peoples R China; [Jin, Feng] Guizhou Med Univ, Affiliated Tumor Hosp, Dept Head & Neck Oncol, Guiyang, Peoples R China; [Meng, Juan] Haikou Peoples Hosp, Dept Med Oncol, Haikou, Peoples R China; [Shi, Jianhua] Linyi Canc Hosp, Dept Med Oncol, Linyi, Peoples R China; [Wang, Peiguo] Tianjin Med Univ, Canc Inst & Hosp, Dept Oncol Radiotherapy, Tianjin, Peoples R China; [Cui, Jiuwei] First Hosp Jilin Univ, Dept Med Oncol, Changchun, Peoples R China; [Yang, Kunyu] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Med Oncol, Wuhan, Peoples R China; [Zhang, Xuebang] Wenzhou Med Univ, Affiliated Hosp 1, Dept Med Oncol, Wenzhou, Peoples R China; [Li, Xiaojiang] Yunnan Canc Hosp, Dept Head & Neck Surg, Kunming, Peoples R China; [Shen, Liangfang; He, Yuxiang] Cent South Univ, Xiangya Hosp, Dept Med Oncol, Changsha, Peoples R China; [Zhai, Limin] Shandong Canc Hosp, Dept Head & Neck Neoplasm, Jinan, Peoples R China; [Sun, Xiuhua] Dalian Med Univ, Affiliated Hosp 2, Dept Med Oncol, Dalian, Peoples R China; [Ge, Junyou; Qing, Yan; Zong, Dekang] Sichuan Kelun Biotech Biopharmaceut Co Ltd, Chengdu, Peoples R China"

通信作者："Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Med Oncol, Beijing Key Lab Clin Study Anticanc Mol Targeted, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China.; Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China.; Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China."

来源：LANCET REGIONAL HEALTH-WESTERN PACIFIC

ESI学科分类：　

WOS号：WOS:000975177900001

JCR分区：Q1

影响因子：7.1

年份：2023

卷号：31

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：KL-A167; Nasopharyngeal carcinoma; Efficacy; Safety; PD-L1; Biomarker

摘要："Background KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recur-rent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologi-cally confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or with-drawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade >= 3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previ-ously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)"

基金机构："Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innova-tion [2017ZX09304015]"

基金资助正文："Funding Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innova-tion (2017ZX09304015) ."