Shun Lu1, Qiming Wang2, Guojun Zhang3, Xiaorong Dong4, Cheng-Ta Yang5, Yong Song6, Gee-Chen Chang7, You Lu8, Hongming Pan9, Chao-Hua Chiu10, Zhehai Wang11, Jifeng Feng12, Jianying Zhou13, Xingxiang Xu14, Renhua Guo15, Jianhua Chen16, Haihua Yang17, Yuan Chen18, Zhuang Yu19, Her-Shyong Shiah20, Chin-Chou Wang21, Nong Yang22, Jian Fang23, Ping Wang24, Kai Wang25, Yanping Hu26, Jianxing He27, Ziping Wang23, Jianhua Shi28, Shaoshui Chen29, Qiong Wu30, Changan Sun31, Chuan Li30, Hongying Wei30, Ying Cheng32, Wu-Chou Su33, Te-Chun Hsia34, Jiuwei Cui35, Yuping Sun36, Sai-Hong Ignatius Ou37, Viola W Zhu37, James Chih-Hsin Yang38. 1. Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China. Electronic address: shunlu@sjtu.edu.cn. 2. Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, People's Republic of China. 3. Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China. 4. Cancer Center, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, People's Republic of China. 5. Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. 6. Department of Respiration, General Hospital of The PLA Eastern Theater Command, Nanjing, People's Republic of China. 7. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. 8. Department of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, People's Republic of China. 9. Department of Oncology, Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China. 10. Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 11. Department of Oncology, Shandong Cancer Hospital, Jinan, People's Republic of China. 12. Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People's Republic of China. 13. Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. 14. Department of Respiration, Northern Jiangsu People's Hospital, The Affiliated Hospital to Yangzhou University, Yangzhou, People's Republic of China. 15. Department of Medical Oncology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China. 16. Department of Medical Oncology-Chest, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China. 17. Department of Radiotherapy, Taizhou Hospital of Zhejiang Province, Taizhou, People's Republic of China. 18. Department of Oncology, Tongji Medical College Huazhong University of Science & Technology, Wuhan, People's Republic of China. 19. Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China. 20. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. 21. Department of Occupational Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. 22. Department of Pulmonary Gastroenterology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China. 23. Department of Chest Medicine, Beijing Cancer Hospital, Beijing, People's Republic of China. 24. Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People's Republic of China. 25. Department of Respiration, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China. 26. Department of Thoracic Oncology, Hubei Cancer Hospital, Wuhan, People's Republic of China. 27. Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. 28. Department of Internal Medicine, Linyi Cancer Hospital, Linyi, People's Republic of China. 29. Department of Oncology, Binzhou Medical University Hospital, Binzhou, People's Republic of China. 30. Clinical Medical Group, Jiangsu Hansoh Pharmaceutical Group Co. Ltd., Shanghai, People's Republic of China. 31. Clinical Operation Group, Jiangsu Hansoh Pharmaceutical Group Co. Ltd., Shanghai, People's Republic of China. 32. Department of Internal Medicine, Jilin Cancer Hospital, Changchun, People's Republic of China. 33. Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Taipei, Taiwan. 34. Division of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung, Taiwan. 35. Department of Oncology, The First Bethune Hospital of Jilin University, Changchun, People's Republic of China. 36. Department of Oncology, Jinan Central Hospital, Jinan, People's Republic of China. 37. Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology and Oncology, University of California, Irvine School of Medicine, Orange, California. 38. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Abstract
INTRODUCTION: Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation. METHODS: Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review. RESULTS: A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study. CONCLUSIONS: Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.
INTRODUCTION: Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation. METHODS: Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review. RESULTS: A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study. CONCLUSIONS: Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.
Authors: P Xing; X Zheng; Y Wang; T Chu; S Wang; J Jiang; J Qian; X Han; L Ding; Y Wang; L Cui; H Li; L Li; X Chen; B Han; P Hu; Y Shi Journal: ESMO Open Date: 2022-05-06