@article{ddf0ce7d89a24374a8566a1e0496605d,
title = "Efficacy of Aumolertinib (HS-10296) in Patients With Advanced EGFR T790M+ NSCLC: Updated Post-National Medical Products Administration Approval Results From the APOLLO Registrational Trial",
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.",
keywords = "Almonertinib, Aumolertinib, EGFR T790M mutation, HS-10296, Third-generation EGFR TKI",
author = "Shun Lu and Qiming Wang and Guojun Zhang and Xiaorong Dong and Yang, {Cheng Ta} and Yong Song and Chang, {Gee Chen} and You Lu and Hongming Pan and Chiu, {Chao Hua} and Zhehai Wang and Jifeng Feng and Jianying Zhou and Xingxiang Xu and Renhua Guo and Jianhua Chen and Haihua Yang and Yuan Chen and Zhuang Yu and Shiah, {Her Shyong} and Wang, {Chin Chou} and Nong Yang and Jian Fang and Ping Wang and Kai Wang and Yanping Hu and Jianxing He and Ziping Wang and Jianhua Shi and Shaoshui Chen and Qiong Wu and Changan Sun and Chuan Li and Hongying Wei and Ying Cheng and Su, {Wu Chou} and Hsia, {Te Chun} and Jiuwei Cui and Yuping Sun and Ou, {Sai Hong Ignatius} and Zhu, {Viola W.} and {Chih-Hsin Yang}, James",
note = "Funding Information: Disclosure: Dr. S. Lu reports receiving grants and personal fees from Hansoh Pharmaceutical Group Co., Ltd., Hutchison MediPharma, and Heng Rui Therapeutics; grants, personal fees, and others from AstraZeneca and Roche; grants from Bristol-Myers Squibb and BeiGene; personal fees from Pfizer , Boehringer Ingelheim , Simcere, ZaiLab, GenomiCare, Yuhan Corporation, PrIME Oncology, Menarini, and InventisBio Co., Ltd.; and other support from Regeneron and Xcovery Holding, outside of the submitted work. Drs. Q. Wang, Zhang, Song, Y. Lu, Pan, Zhehai Wang, Feng, Zhou, Xu, H. Yang, Yuan Chen, Yu, N. Yang, Fang, P. Wang, K. Wang, Hu, He, Ziping Wang, Shi, Cheng, Cui, and Y. Sun report receiving grants from Hansoh Pharmaceutical Group Co., Ltd., during the conduct of the study and outside of the submitted work. Drs. Dong, C.-T. Yang, Chang, Chiu, Guo, J. Chen, Shiah, C.-C. Wang, S. Chen, and T.-C. Hsia report receiving personal fees and nonfinancial support from Hansoh Pharmaceutical Group Co., Ltd., outside of the submitted work. Dr. Y. Lu reports receiving a grant from West China Hospital of Sichuan University . Dr. Su reports receiving personal fees and nonfinancial support from Hansoh Pharmaceutical Group Co., Ltd., Roche , and Merck Sharp & Dohme, outside of the submitted work. Dr. Ou reports receiving personal fees from Pfizer, Merck , Takeda , AstraZeneca, Roche-Genentech, Daiichi Sankyo, Johnson & Johnson-Janseen, and X-Covery LLC and other support from Turning Point Therapeutics and Elevation Oncology, outside of the submitted work. Dr. Zhu reports receiving other support from AstraZeneca , Blueprint, Roche-Foundation Medicine, Roche-Genentech, Takeda, TP Therapeutics, and Xcovery, outside of the submitted work. Dr. C.-H. Yang reports receiving personal fees and nonfinancial support from Hansoh Pharmaceutical Group Co., Ltd., Boehringer Ingelheim, Chugai Pharmaceutical , Merck Sharp & Dohme, AstraZeneca, Roche, Genentech, and Bayer AG, outside of the submitted work. Drs. Wu, Wei, Mr. C. Sun, and Mr. Li are employees of Hansoh Pharmaceutical Group Co., Ltd., and report receiving personal fees from Hansoh Pharmaceutical Group Co., Ltd., during the conduct of the study and outside of the submitted work. Funding Information: This work was supported by Hansoh Pharmaceutical Group Co., Ltd., The National Key R&D Program of China (2016YFC1303300), and the Shanghai Science and Technology Innovation Program (19411950500). The authors thank all patients and their families, along with the investigators and staffs at the participating centers. We also thank the study teams from Hansoh Pharmaceutical Group Co., Ltd., including Xiaoling Qian, Qiang Zhang, Wanyi Huang, Yong Yang, Xue Sun, and Qiu Sun, for their support, the Teddy Clinical Research Laboratory (Shanghai, People{\textquoteright}s Republic of China) for EGFR mutation test, and the Fantastic Bioimaging (Shanghai, People{\textquoteright}s Republic of China) for independent central review assessment. Funding Information: Disclosure: Dr. S. Lu reports receiving grants and personal fees from Hansoh Pharmaceutical Group Co., Ltd., Hutchison MediPharma, and Heng Rui Therapeutics; grants, personal fees, and others from AstraZeneca and Roche; grants from Bristol-Myers Squibb and BeiGene; personal fees from Pfizer, Boehringer Ingelheim, Simcere, ZaiLab, GenomiCare, Yuhan Corporation, PrIME Oncology, Menarini, and InventisBio Co., Ltd.; and other support from Regeneron and Xcovery Holding, outside of the submitted work. Drs. Q. Wang, Zhang, Song, Y. Lu, Pan, Zhehai Wang, Feng, Zhou, Xu, H. Yang, Yuan Chen, Yu, N. Yang, Fang, P. Wang, K. Wang, Hu, He, Ziping Wang, Shi, Cheng, Cui, and Y. Sun report receiving grants from Hansoh Pharmaceutical Group Co., Ltd., during the conduct of the study and outside of the submitted work. Drs. Dong, C.-T. Yang, Chang, Chiu, Guo, J. Chen, Shiah, C.-C. Wang, S. Chen, and T.-C. Hsia report receiving personal fees and nonfinancial support from Hansoh Pharmaceutical Group Co., Ltd., outside of the submitted work. Dr. Y. Lu reports receiving a grant from West China Hospital of Sichuan University. Dr. Su reports receiving personal fees and nonfinancial support from Hansoh Pharmaceutical Group Co., Ltd., Roche, and Merck Sharp & Dohme, outside of the submitted work. Dr. Ou reports receiving personal fees from Pfizer, Merck, Takeda, AstraZeneca, Roche-Genentech, Daiichi Sankyo, Johnson & Johnson-Janseen, and X-Covery LLC and other support from Turning Point Therapeutics and Elevation Oncology, outside of the submitted work. Dr. Zhu reports receiving other support from AstraZeneca, Blueprint, Roche-Foundation Medicine, Roche-Genentech, Takeda, TP Therapeutics, and Xcovery, outside of the submitted work. Dr. C.-H. Yang reports receiving personal fees and nonfinancial support from Hansoh Pharmaceutical Group Co., Ltd., Boehringer Ingelheim, Chugai Pharmaceutical, Merck Sharp & Dohme, AstraZeneca, Roche, Genentech, and Bayer AG, outside of the submitted work. Drs. Wu, Wei, Mr. C. Sun, and Mr. Li are employees of Hansoh Pharmaceutical Group Co., Ltd., and report receiving personal fees from Hansoh Pharmaceutical Group Co., Ltd., during the conduct of the study and outside of the submitted work. Publisher Copyright: {\textcopyright} 2021 International Association for the Study of Lung Cancer",
year = "2022",
month = mar,
doi = "10.1016/j.jtho.2021.10.024",
language = "English",
volume = "17",
pages = "411--422",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "3",
}