Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/ Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study

作者全名："Shi, Yuankai; Wu, Shiman; Wang, Ke; Cang, Shundong; Yao, Wenxiu; Fan, Yun; Wu, Lin; Huang, Meijuan; Li, Xingya; Pan, Yueyin; Yang, Zhixiong; Zhu, Bo; Chen, Gongyan; Shi, Jianhua; Sun, Meili; Fang, Jian; Wang, Lijun; Chen, Zhaohong; Liu, Chunling; Li, Jingzhang; Liu, Jiwei; Sun, Shenghua; Zhao, Yanqiu; Guo, Yanzhen; Meng, Zili; Liu, Zhefeng; Han, Zhigang; Lu, Hong; Ma, Rui; Hu, Sheng; Zhao, Guofang; Liu, Zheng; Xie, Congying; Zhong, Diansheng; Zhao, Hui; Yu, Huiqing; Zhang, Longzhen; Bi, Minghong; Yi, Shanyong; Guo, Shuliang; Yi, Tienan; Li, Wen; Lin, Yingcheng; Shu, Yongqian; Chen, Zhendong; Guo, Zhongliang; Greco, Michael; Wang, Tingting; Shen, Haijiao"

作者地址："[Shi, Yuankai; Wang, Ke] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc, Beijing, Peoples R China; [Cang, Shundong] Shanxi Med Univ, Hosp 1, Dept Resp Med, Taiyuan, Peoples R China; [Yao, Wenxiu] West China Hosp Sichuan Univ, Dept Resp & Crit Care Med, Chengdu, Peoples R China; [Fan, Yun] Henan Prov Peoples Hosp, Dept Med Oncol, Zhengzhou, Peoples R China; [Wu, Lin] Sichuan Canc Hosp, Dept Med Oncol, Chengdu, Peoples R China; [Huang, Meijuan] Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China; [Li, Xingya] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Xiangya Sch Med,Dept Thorac Med Oncol, Changsha, Peoples R China; [Pan, Yueyin] Sichuan Univ, West China Hosp, Dept Oncol, Chengdu, Peoples R China; [Yang, Zhixiong] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou, Peoples R China; [Zhu, Bo] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Thorac Canc Chemotherapy, Div Life Sci & Med, Hefei, Peoples R China; [Chen, Gongyan] Guangdong Med Univ, Affiliated Hosp, Canc Ctr, Zhanjiang, Peoples R China; [Fang, Jian] Third Mil Med Univ, Xinqiao Hosp, Inst Canc, Dept Oncol, Chongqing, Peoples R China; [Chen, Zhaohong] Harbin Med Univ Canc Hosp, Dept Resp Med, Harbin, Peoples R China; [Shi, Jianhua] Linyi Canc Hosp, Dept Med Oncol, Linyi, Peoples R China; [Sun, Meili] Shandong Univ, Jinan Cent Hosp, Dept Oncol, Jinan, Peoples R China; [Fang, Jian] Beijing Canc Hosp, Dept Thorac Oncol, Beijing, Peoples R China; [Wang, Lijun] Xingtai Med Coll, Affiliated Hosp 2, Canc Ctr, Xingtai, Peoples R China; [Chen, Zhaohong] Peoples Hosp Deyang City, Dept Oncol, Deyang, Peoples R China; [Liu, Chunling; Han, Zhigang] Xinjiang Med Univ, Affiliated Tumor Hosp, Pulm Canc Med, Urumqi, Peoples R China; [Li, Jingzhang] Liuzhou Peoples Hosp, Dept Oncol, Liuzhou, Peoples R China; [Liu, Jiwei] Dalian Med Univ, Affiliated Hosp 1, Dept Oncol, Dalian, Peoples R China; [Sun, Shenghua] Cent South Univ, Xiangya Hosp 3, Dept Resp Med, Changsha, Peoples R China; [Zhao, Yanqiu] Zhengzhou Univ, Affiliated Canc Hosp, Dept Resp Med, Zhengzhou, Peoples R China; [Guo, Yanzhen] Henan Univ Sci & Technol, Affiliated Hosp 1, Dept Med Oncol, Luoyang, Peoples R China; [Meng, Zili] Nanjing Med Univ, Affiliated Huaian Peoples Hosp 1, Dept Resp Med, Huaian, Peoples R China; [Liu, Zhefeng] Chinese Peoples Liberat Army Gen Hosp, Dept Oncol, Beijing, Peoples R China; [Lu, Hong] Henan Univ, Dept Oncol, Huaihe Hosp, Kaifeng, Peoples R China; [Ma, Rui] Liaoning Canc Hosp & Inst, Dept Thorac Oncol, Shenyang, Peoples R China; [Hu, Sheng] Hubei Canc Hosp, Dept Thorac Oncol, Wuhan, Peoples R China; [Zhao, Guofang] Univ Chinese Acad Sci, Hwa Mei Hosp, Dept Thorac Surg, Ningbo, Peoples R China; [Liu, Zheng] Handan Cent Hosp, Dept Oncol, Handan, Peoples R China; [Xie, Congying] First Affiliated Hosp Wenzhou Med Univ, Dept Radiotherapy, Wenzhou, Peoples R China; [Zhong, Diansheng] Tianjin Med Univ Gen Hosp, Dept Med Oncol, Tianjin, Peoples R China; [Zhao, Hui] Second Hosp Anhui Med Univ, Dept Resp Med, Hefei, Peoples R China; [Yu, Huiqing] Chongqing Univ Canc Hosp, Dept Palliat Care, Dept Geriatr Oncol, Chongqing, Peoples R China; [Zhang, Longzhen] Affiliated Hosp Xuzhou Med Univ, Dept Radiotherapy, Xuzhou, Peoples R China; [Bi, Minghong] First Affiliated Hosp Bengbu Med Coll, Dept Med Oncol, Bengbu, Peoples R China; [Yi, Shanyong] Zhengzhou Cent Hosp Affiliated Zhengzhou Univ, Dept Med Oncol, Zhengzhou, Peoples R China; [Guo, Shuliang] First Affiliated Hosp Chongqing Med Univ, Dept Resp Med, Chongqing, Peoples R China; [Yi, Tienan] Xiangyang Cent Hosp, Affiliated Hosp Hubei Univ Arts & Sci, Dept Oncol, Xiangyang, Peoples R China; [Li, Wen] Second Affiliated Hosp Zhejiang Univ Sch Med, Dept Resp & Crit Care Med, Hangzhou, Peoples R China; [Lin, Yingcheng] Canc Hosp Shantou Univ Med Coll, Dept Med Oncol, Shantou, Peoples R China; [Shu, Yongqian] Jiangsu Prov Hosp, Dept Oncol, Nanjing, Peoples R China; [Chen, Zhendong] Second Hosp Anhui Med Univ, Dept Oncol, Hefei, Peoples R China; [Guo, Zhongliang] Shanghai East Hosp, Dept Resp Med, Shanghai, Peoples R China; [Greco, Michael] Beta Pharm Inc, Dept Drug Discovery, Princeton, NJ USA; [Wang, Tingting; Shen, Haijiao] Beta Pharm Shanghai Co Ltd, Dept Clin Dev, Shanghai, Peoples R China; [Shi, Yuankai] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China"

通信作者："Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc, Beijing, Peoples R China.; Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China."

来源：JOURNAL OF THORACIC ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000919159500010

JCR分区：Q1

影响因子：20.4

年份：2022

卷号：17

期号：11

开始页：1306

结束页：1317

文献类型：Article

关键词：Rezivertinib; BPI-7711; NSCLC; EGFR T790M mutation; Third-generation EGFR TKI

摘要："Introduction: Rezivertinib (BPI-7711) is a novel third -generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M muta-tion. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/ recurrent EGFR T790M-mutated NSCLC. Methods: Patients with locally advanced or metastatic/ recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or with-drawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). Results: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equalto one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported.Conclusions: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.(c) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)."

基金机构："Beta Pharma (Shanghai) Co., Ltd., Shanghai, People's Republic of China [NCT03812809]; China National Major Project for New Drug Innovation [2017ZX09304015]; New National Natural Science Foundation of China [81972805, 82172856]"

基金资助正文："This study (NCT03812809) was funded by Beta Pharma (Shanghai) Co., Ltd., Shanghai, People's Republic of China, and partly supported by China National Major Project for New Drug Innovation (2017ZX09304015) and New National Natural Science Foundation of China (81972805 and 82172856). The authors thank all the patients and their families for participating in this study and the clinical study team. The authors thank Dr. Liling Huang and Dr. Haizhu Chen (National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, People's Republic of China) for manuscript editing assistance."