获取途径

作者

Yuankai Shi, Jian Fang, Xuezhi Hao, Shucai Zhang, Yunpeng Liu, Lin Wang, Jianhua Chen, Yi Hu, Xiaosheng Hang, Juan Li, Chunling Liu, Yiping Zhang, Zhehai Wang, Yanping Hu, Kangsheng Gu, Jian'an Huang, Liangming Zhang, Jinlu Shan, Weiwei Ouyang, Yanqiu Zhao, Wu Zhuang, Yan Yu, Jun Zhao, Helong Zhang, Pei Lu, Weidong Li, Meimei Si, Mingjing Ge, Huaize Geng

作者单位

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, 100021, Beijing, P.R. China. syuankai@cicams.ac.cn. Hunan Cancer Hospital, 410000, Changsha, P.R. China. Beijing Chest Hospital, Capital Medical University, 101149, Beijing, P.R. China. Affiliated Hospital of Jiangnan University, 214062, Wuxi, P.R. China. Sichuan Cancer Hospital, 610041, Chengdu, P.R. China. 10 Affiliated Tumour Hospital of Xinjiang Medical University, 830000, Urumqi, P.R. China. 11 Zhejiang Cancer Hospital, 310022, Hangzhou, P.R. China. 12 Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 250117, Jinan, P.R. China. 13 Hubei Cancer Hospital, 430079, Wuhan, P.R. China. 14 The First Affiliated Hospital of Anhui Medical University, 230022, Hefei, P.R. China. 15 The First Affiliated Hospital of Soochow University, 215006, Suzhou, P.R. China. 16 Yantai Yuhuagding Hospital, Yantai, 264000, P.R. China. 17 Army Medical Center of People's Liberation Army, 400042, Chongqing, P.R. China. 18 Guizhou Cancer Hospital, 520100, Guiyang, P.R. China. 19 Henan Cancer Hospital, 450008, Zhengzhou, P.R. China. 20 Fujian Province Cancer Hospital, 350014, Fuzhou, P.R. China. 21 Harbin Medical University Cancer Hospital, 150081, Harbin, P.R. China. 22 Tangdu Hospital of the Fourth Military Medical University, 710038, Xi'an, P.R. China. 23 Liuzhou People's Hospital, 545006, Liuzhou, P.R. China. 24 Cancer Center of Guangzhou Medical University, 510095, Guangzhou, P.R. China. 25 Qilu Pharmaceutical Co., Ltd, 250101, Jinan, P.R. China. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, 100021, Beijing, P.R. China. Beijing Cancer Hospital, 100142, Beijing, P.R. China. Chinese PLA General Hospital, 100853, Beijing, P.R. China. The First Hospital of China Medical University, 110001, Shenyang, P.R. China. Affiliations

刊名

Signal transduction and targeted therapy

年份

2022

卷号

Vol.7 No.1

页码

25

ISSN

2059-3635

摘要

WX-0593 is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor . In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dos...更多

WX-0593 is a novel, highly selective oral ALK and ROS1 tyrosine kinase inhibitor . In this study, the safety, antitumor activity, and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer patients with ALK or ROS1 rearrangement. In the dose-escalation phase and dose-expansion phase, patients were treated with WX-0593 until disease progression, unacceptable toxicity, or subject withdrawal. In the dose-escalation phase, the primary endpoints were maximum tolerated dose , dose-limiting toxicity , and safety assessed by investigators. In the dose-expansion phase, the primary endpoint was objective response rate assessed by investigators. Between September 25, 2017 and October 15, 2018, a total of 153 patients received WX-0593 treatment. Two dose-limiting toxicities including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient. MTD was not reached. Overall, 140 of the 152 patients experienced treatment-related adverse events and 35 of the 152 patients had TRAEs ≥grade 3. The overall ORR was 59.3% for the dose-escalation phase and 56.6% for the dose-expansion phase. For patients who were ALK-rearranged and ALK TKI naive, the ORR were 81.0% in the dose-escalation phase and 76.3% in the dose-expansion phase, and for patients who previously received crizotinib as the only ALK TKI, the ORR were 38.1% and 45.7% for the two phases, respectively. For patients who were ROS1-rearranged, the ORR were 30.0% in the dose-escalation phase and 44.4% in the dose-expansion phase. WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.收起

文献类型

期刊