KL-A167用于既往接受过治疗的复发或转移性鼻咽癌的疗效和安全性：一项多中心、单臂、2期研究。
Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.
作者信息
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
机构信息
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center and National Clinical Research Center for Cancer and Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Medical Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
出版信息
Lancet Reg Health West Pac. 2022 Oct 10;31:100617. doi: 10.1016/j.lanwpc.2022.100617. eCollection 2023 Feb.
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 recurrent 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 histologically 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 withdrawal 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 previously 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.
FUNDING
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).
背景
KL-A167是一种靶向程序性细胞死亡配体1的全人源单克隆抗体。这项2期研究旨在评估KL-A167在中国既往接受过治疗的复发或转移性（R/M）鼻咽癌（NPC）患者中的疗效和安全性。
方法
这是一项在中华人民共和国42家医院开展的关于KL-A167治疗R/M NPC的多中心、单臂、2期研究（KL167-2-05-CTP）（NCT03848286）。符合条件的患者经组织学确诊为非角化型R/M NPC，且至少接受过两线化疗失败。患者每2周静脉注射一次900mg KL-A167，直至确认疾病进展、出现无法耐受的毒性或撤回知情同意书。主要终点是由独立审查委员会（IRC）根据RECIST v1.1评估的客观缓解率（ORR）。
结果
在2019年2月26日至2021年1月13日期间，共治疗了153例患者。总计132例患者进入全分析集（FAS）并接受疗效评估。截至2021年7月13日的数据截止日期，中位随访时间为21.7个月（95%CI 19.8 - 22.5）。对于FAS人群，IRC评估的ORR为26.5%（95%CI 19.2 - 34.9%），疾病控制率（DCR）为56.8%（95%CI 47.9 - 65.4%）。中位无进展生存期（PFS）为2.8个月（95%CI 1.5 - 4.1）。中位缓解持续时间为12.4个月（95%CI 6.8 - 16.5），中位总生存期（OS）为16.2个月（95%CI 13.4 - 21.3）。当将血浆EBV DNA滴度的截断值设定为1000拷贝/ml、5000拷贝/ml和10000拷贝/ml时，基线血浆EBV DNA水平较低始终与更好的DCR、PFS和OS相关。血浆EBV DNA的动态变化与ORR和PFS显著相关。在153例患者中，73.2%的患者发生了治疗相关不良事件（TRAEs），≥3级TRAEs的患者占15.0%。未报告导致死亡的TRAEs。
结论
在本研究中，KL-A167在既往接受过治疗的R/M NPC患者中显示出有前景的疗效和可接受的安全性。基线血浆EBV DNA拷贝数可能是KL-A167治疗潜在有用的预后生物标志物，治疗后EBV DNA降低可能与对KL-A167的更好反应相关。
资助
四川科伦博泰生物医药股份有限公司，国家重大新药创制专项（2017ZX09304015）
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