Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study
Yuankai Shi, Shiman Wu, Ke Wang, Shundong Cang, Wenxiu Yao, Yun Fan, Lin Wu, Meijuan Huang, Xingya Li, Yueyin Pan, Zhixiong Yang, Bo Zhu, Gongyan Chen, Jianhua Shi, Meili Sun, Jian Fang, Lijun Wang, Zhaohong Chen, Chunling Liu, Jingzhang Li, Jiwei Liu, Shenghua Sun, Yanqiu Zhao, Yanzhen Guo, Zili Meng, Zhefeng Liu, Zhigang Han, Hong Lu, Rui Ma, Sheng Hu, Guofang Zhao, Zheng Liu, Congying Xie, Diansheng Zhong, Hui Zhao, Huiqing Yu, Longzhen Zhang, Minghong Bi, Shanyong Yi, Shuliang Guo, Tienan Yi, Wen Li, Yingcheng Lin, Yongqian Shu, Zhendong Chen, Zhongliang Guo, Michael Greco, Tingting Wang, Haijiao Shen, Yuankai Shi, Shiman Wu, Ke Wang, Shundong Cang, Wenxiu Yao, Yun Fan, Lin Wu, Meijuan Huang, Xingya Li, Yueyin Pan, Zhixiong Yang, Bo Zhu, Gongyan Chen, Jianhua Shi, Meili Sun, Jian Fang, Lijun Wang, Zhaohong Chen, Chunling Liu, Jingzhang Li, Jiwei Liu, Shenghua Sun, Yanqiu Zhao, Yanzhen Guo, Zili Meng, Zhefeng Liu, Zhigang Han, Hong Lu, Rui Ma, Sheng Hu, Guofang Zhao, Zheng Liu, Congying Xie, Diansheng Zhong, Hui Zhao, Huiqing Yu, Longzhen Zhang, Minghong Bi, Shanyong Yi, Shuliang Guo, Tienan Yi, Wen Li, Yingcheng Lin, Yongqian Shu, Zhendong Chen, Zhongliang Guo, Michael Greco, Tingting Wang, Haijiao Shen
Abstract
Introduction: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. 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 withdrawal 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 equal to 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.
Keywords: BPI-7711; EGFR T790M mutation; NSCLC; Rezivertinib; Third-generation EGFR TKI.
Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Source: PubMed