机构：[1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China广东省人民医院[2]Department of Medical Oncology, Second Chest Cancer Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China[3]Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China[4]Department of Thoracic Oncology, Peking University Cancer Hospital & Institute, Beijing, China[5]Department of Respiratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China浙江大学医学院附属第一医院[6]Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China[7]Department of Lung Cancer, Fifth Medical Center of PLA General Hospital, Beijing, China[8]Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, China四川大学华西医院[9]Division of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China[10]Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China[11]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China[12]The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China[13]Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China[14]Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China[15]Department of Respiratory Medicine, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China[16]Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China[17]Oncology Department, Chinese PLA General Hospital, Beijing, China[18]Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China江苏省人民医院[19]Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, China[20]ACEA Pharmaceutical Research, Hangzhou, China[21]ACEA Therapeutics Inc., San Diego, CA, USA
To establish RP2D in Phase 1 and evaluate safety and efficacy of abivertinib in EGFR T790M+ NSCLC patients with disease progression from prior EGFR inhibitors in Phase 2.This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50mg BID to 350 mg BID was evaluated in Phase 1 in continual 28-day cycles, and the RP2D of 300 mg BID was used in Phase 2 in continual 21-day cycles. Primary endpoints include RP2D in phase 1 and objective response rate (ORR) at RP2D in phase 2.The RP2D of 300 mg BID for abivertinib was established based on pharmacokinetics, efficacy and safety profiles across doses in Phase 1. In Phase 2, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response evaluable patients, confirmed ORR was 52.2% (109/209; 95% CI: 45.2%, 59.1%). Disease control rate (DCR) was 88.0% (184/209, 95% CI: 82.9%, 92.1%). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1, 9.2) and 7.5 months (95% CI: 6.0, 8.8), respectively. The median OS was 24.9 months (95% CI: 22.4, NR). All (227/227) patients reported at least 1 AE, with 96.9% (220/227) of treatment-related AE. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment related.Abivertinib of 300 mg BID demonstrated favorable clinical efficacy with manageable side-effects in patients with EGFR T790M+NSCLC.
基金：
This research was supported by Key Lab System Project of Guangdong Science and
Technology Department – Guangdong Provincial Key Lab of Translational Medicine
in Lung Cancer (Grant No. 2017B030314120, to Y.L. WU); High-level Hospital
Construction Project (Grant No.DFJH201810, to Q. Zhou) and National Science and
Technology Infrastructure Program (National Key Science Projects Program, Grant
No. 2018ZX09301-014-002, to W.H. Xu, W. Tang, X. Zhang and X. Xiao).
This study was funded by ACEA Pharmaceutical Research, Hangzhou, China.
第一作者机构：[1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
通讯作者：
通讯机构：[1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China[*1]Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Science, No.106 Zhongshan 2nd Rd, Guangzhou 510080, China
推荐引用方式(GB/T 7714)：
Qing Zhou,Lin Wu,Pei Hu,et al.A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study.[J].CLINICAL CANCER RESEARCH.2022,28(6):1127-1135.doi:10.1158/1078-0432.CCR-21-2595.
APA：
Qing Zhou,Lin Wu,Pei Hu,Tongtong An,Jianying Zhou...&Yi-Long Wu.(2022).A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study..CLINICAL CANCER RESEARCH,28,(6)
MLA：
Qing Zhou,et al."A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study.".CLINICAL CANCER RESEARCH 28..6(2022):1127-1135
医学