Efficacy and safety of iruplinalkib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT).

Yu Zhang, Jun Zhao, Mengzhao Wang, Liangming Zhang, Sanyuan Sun, Yanping Hu, Kangsheng Gu, Xiaosheng Hang, Jinlu Shan, Yan Yu, Bangxian Tan, Weihua Yang, Runxiang Yang, Meimei Si, Huaize Geng, Hui Li, Xiaoyan Kang, Yuankai Shi, Yunpeng Liu, Lin Wang, Xuezhi Hao, Lei Yang, Changlu Hu, Yanqiu Zhao, Xiuwen Wang, Chunling Liu, Jian Zhao, Shucai Zhang, Zhehai Wang, Yiping Zhang, Zhihong Zhang, Helong Zhang, Jianhua Chen

Journal: BMC medicine 2023;21(1):72

PMID: 36829154

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Abstract

BACKGROUND

Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients.

METHODS

ALK-positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0-2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR).

RESULTS

From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval [CI] 16.8-18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7-77.2%) and 96.6% (95% CI 92.2-98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6-70.8%) and 94.5% (95% CI 89.5-97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4-17.7) and 14.5 months (95% CI 11.7-20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1-not evaluable [NE]), 19.8 months (95% CI 14.5-NE), and NE (95% CI 14.5-NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35-56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48-78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 [43.2%]), alanine aminotransferase increased (54 [37.0%]), and blood creatine phosphokinase increased (51 [34.9%]). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively.

CONCLUSIONS

In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population.

TRIAL REGISTRATION

Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020.

Address: Department of Medical Oncology, 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, Beijing, China. [email protected].; Thoracic Medicine Department I, Hunan Tumor Hospital, Changsha, China.; Oncology Department, the Second Affiliated Hospital of Air Force Medical University, Xi'an, China.; Department of Respiratory Oncology, Anhui Provincial Cancer Hospital, Hefei, China.; Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.; Respiratory Medical Oncology Ward II, Shandong Provincial Institute of Cancer Prevention and Treatment, Jinan, China.; Oncology Department II, Beijing Chest Hospital, Capital Medical University, Beijing, China.; Thoracic Surgery I, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.; Pulmonary Medicine Ward II, The Affiliated Tumour Hospital of Xingjiang Medical University, Urumqi, China.; Chemotherapy Department, Qilu Hospital of Shandong University, Jinan, China.; Respiratory Medicine Ward I, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.; Ward IV of Department of Oncology, Anhui Provincial Cancer Hospital, Hefei, China.; Department of Respiratory Oncology, Gansu Province Cancer Hospital, Lanzhou, China.; Department of Medical Oncology, 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, Beijing, China.; Department of Medical Oncology Ward II, The First Hospital of China Medical University, Shenyang, China.; Respiratory Medicine Ward III, Harbin Medical University Cancer Hospital, Harbin, China.; Department of Thoracic Oncology I, Peking University Cancer Hospital, Beijing, China.; Department of Pulmonary and Critical care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.; Oncology Department, Yantai Yuhuangding Hospital, Yantai, China.; Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, China.; Thoracic Oncology (2), Hubei Cancer Hospital, Wuhan, China.; Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.; Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.; Oncology Department, Army Medical Center of PLA, Chongqing, China.; Respiratory Department, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, China.; Department of Oncology, Affiliated Hospital of North Sichuan Medical college, Nanchong, China.; Department of Respiratory, Shanxi Provincial Cancer Hospital, Taiyuan, China.; The Second Department of Medical Oncology, Yunnan Cancer Hospital, Kunming, China.; Clinical Research Center, Qilu Pharmaceutical Co., Ltd., Jinan, China.

DOI: 10.1186/s12916-023-02738-5

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MeSH Terms: Humans, Adolescent, Adult, Carcinoma, Non-Small-Cell Lung, Crizotinib, Lung Neoplasms, Protein-Tyrosine Kinases, Anaplastic Lymphoma Kinase, Proto-Oncogene Proteins, Protein Kinase Inhibitors