Safety, Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study
Yuankai Shi, Yanqiu Zhao, Sheng Yang, Jianying Zhou, Liangming Zhang, Gongyan Chen, Jian Fang, Bo Zhu, Xingya Li, Yongqian Shu, Jianhua Shi, Rongsheng Zheng, Donglin Wang, Huiqing Yu, Jianan Huang, Zhixiang Zhuang, Gang Wu, Longzhen Zhang, Zhongliang Guo, Michael Greco, Xiao Li, Yu Zhang, Yuankai Shi, Yanqiu Zhao, Sheng Yang, Jianying Zhou, Liangming Zhang, Gongyan Chen, Jian Fang, Bo Zhu, Xingya Li, Yongqian Shu, Jianhua Shi, Rongsheng Zheng, Donglin Wang, Huiqing Yu, Jianan Huang, Zhixiang Zhuang, Gang Wu, Longzhen Zhang, Zhongliang Guo, Michael Greco, Xiao Li, Yu Zhang
Abstract
Introduction: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor selective for EGFR-sensitizing and T790M mutations. This study was designed to evaluate the safety, efficacy, and pharmacokinetics of rezivertinib for patients having advanced NSCLC with EGFR T790M mutation.
Methods: This phase 1 study (NCT03386955) was conducted across 20 sites in the People's Republic of China. Patients received rezivertinib at six oral dose levels (30 mg, 60 mg, 120 mg, 180 mg, 240 mg, 300 mg) once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary end points were safety for the dose-escalation phase and objective response rate by the blinded independent central review for the total study population.
Results: A total of 19 patients in dose-escalation phase using the standard 3 + 3 design principle and 153 patients in dose-expansion phase were enrolled from September 11, 2017, to August 23, 2019. The data cutoff date was on June 15, 2020. No dose-limiting toxicity occurred in the dose-escalation phase. The treatment-related adverse events were observed in 82.0% (141 of 172) of patients, and 17.4% (30 of 172) had grade greater than or equal to 3, among which decreased neutrophil count (2.9%), leukopenia (2.9%), and pneumonia (2.9%) were the most common. The overall blinded independent central review-evaluated objective response rate was 59.3% (102 of 172, 95% confidence interval: 51.6-66.7), and the median progression-free survival was 9.7 (95% confidence interval: 8.3-11.1) months.
Conclusions: Rezivertinib was found to have promising efficacy with a manageable safety profile in patients with EGFR T790M-mutated advanced NSCLC. Further study is warranted.
Keywords: EGFR T790M mutation; Efficacy; NSCLC; Rezivertinib; Safety.
Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Source: PubMed