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Safety and activity of WX-0593(Iruplinalkib)in patients with ALK-or ROS1-rearranged advanced non-small cell lung cancer:a phase 1 dose-escalation and dose-expansion trial

查看全文 作　　者：Yuankai [1]Shi;Jian [2]Fang;Xuezhi [1]Hao;Shucai [3]Zhang;Yunpeng [4]Liu;Lin [1]Wang;Jianhua [5]Chen;Yi [6]Hu;Xiaosheng [7]Hang;Juan [8]Li;Chunling [9]Liu;Yiping [10]Zhang;Zhehai [11]Wang;Yanping [12]Hu;Kangsheng [13]Gu;Jian’an [14]Huang;Liangming [15]Zhang;Jinlu [16]Shan;Weiwei [17]Ouyang;Yanqiu [18]Zhao;Wu [19]Zhuang;Yan [20]Yu;Jun [2]Zhao;Helong [21]Zhang;Pei [22]Lu;Weidong [23]Li;Meimei [24]Si;Mingjing [24]Ge;Huaize [24]Geng 高影响力作者 机构地区：[1]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;[2]Beijing Cancer Hospital,100142 Beijing,P.R.China;[3]Beijing Chest Hospital,Capital Medical University,101149 Beijing,P.R.China;[4]The First Hospital of China Medical University,110001 Shenyang,P.R.China;[5]Hunan Cancer Hospital,410000 Changsha,P.R.China;[6]Chinese PLA General Hospital,100853 Beijing,P.R.China;[7]Affiliated Hospital of Jiangnan University,214062 Wuxi,P.R.China;[8]Sichuan Cancer Hospital,610041 Chengdu,P.R.China;[9]Affiliated Tumour Hospital of Xinjiang Medical University,830000 Urumqi,P.R.China;[10]Zhejiang Cancer Hospital,310022 Hangzhou,P.R.China;[11]Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,250117 Jinan,P.R.China;[12]Hubei Cancer Hospital,430079 Wuhan,P.R.China;[13]The First Affiliated Hospital of Anhui Medical University,230022 Hefei,P.R.China;[14]The First Affiliated Hospital of Soochow University,215006 Suzhou,P.R.China;[15]Yantai Yuhuagding Hospital,Yantai 264000,P.R.China;[16]Army Medical Center of People’s Liberation Army,400042 Chongqing,P.R.China;[17]Guizhou Cancer Hospital,520100 Guiyang,P.R.China;[18]Henan Cancer Hospital,450008 Zhengzhou,P.R.China;[19]Fujian Province Cancer Hospital,350014 Fuzhou,P.R.China;[20]Harbin Medical University Cancer Hospital,150081 Harbin,P.R.China;[21]Tangdu Hospital of the Fourth Military Medical University,710038 Xi’an,P.R.China;[22]Liuzhou People’s Hospital,545006 Liuzhou,P.R.China;[23]Cancer Center of Guangzhou Medical University,510095 Guangzhou,P.R.China;[24]Qilu Pharmaceutical Co.,Ltd,250101 Jinan,P.R.China高影响力机构 出　　处：《Signal Transduction and Targeted Therapy》索引2022年第7卷第2期,共10页高影响力期刊 基　　金：This study(NCT03389815)was funded by Qilu Pharmaceutical Co.,Ltd.and also supported in part by China National Major Project for New Drug Innovation(2017ZX09304015);Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-001). 摘　　要：WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)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(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)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(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement. 关 键 词：PATIENTS EXPANSION PHASE
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