2. Academic Validation
  3. 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

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

  • Signal Transduct Target Ther. 2022 Jan 28;7(1):25. doi: 10.1038/s41392-021-00841-8.
Yuankai Shi 1,  Jian Fang 2,  Xuezhi Hao 3,  Shucai Zhang 4,  Yunpeng Liu 5,  Lin Wang 3,  Jianhua Chen 6,  Yi Hu 7,  Xiaosheng Hang 8,  Juan Li 9,  Chunling Liu 10,  Yiping Zhang 11,  Zhehai Wang 12,  Yanping Hu 13,  Kangsheng Gu 14,  Jian'an Huang 15,  Liangming Zhang 16,  Jinlu Shan 17,  Weiwei Ouyang 18,  Yanqiu Zhao 19,  Wu Zhuang 20,  Yan Yu 21,  Jun Zhao 2,  Helong Zhang 22,  Pei Lu 23,  Weidong Li 24,  Meimei Si 25,  Mingjing Ge 25,  Huaize Geng 25
Affiliations

Affiliations

  • 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. [email protected].
  • 2 Beijing Cancer Hospital, 100142, Beijing, P.R. China.
  • 3 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.
  • 4 Beijing Chest Hospital, Capital Medical University, 101149, Beijing, P.R. China.
  • 5 The First Hospital of China Medical University, 110001, Shenyang, P.R. China.
  • 6 Hunan Cancer Hospital, 410000, Changsha, P.R. China.
  • 7 Chinese PLA General Hospital, 100853, Beijing, P.R. China.
  • 8 Affiliated Hospital of Jiangnan University, 214062, Wuxi, P.R. China.
  • 9 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.
PMID: 35087031 DOI: 10.1038/s41392-021-00841-8
Abstract

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.

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