Background: Almonertinib (HS-10296) is an oral, potent, high selective third generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) for sensitizing mutations and EGFR T790M mutation. The preliminary clinical data of almonertinib reported in WCLC showed favorable efficacy and safety in target populations. Here, we presented the latest efficacy data, including the subgroup analysis of central nervous system (CNS) response. Methods: Patients aged at least 18 years with centrally confirmed EGFR T790M mutation, locally advanced or metastatic non-small cell lung cancer (NSCLC) progressing on prior EGFR-TKI treatment, received almonertinib 110 mg orally once daily until disease progression. Patients with asymptomatic, stable brain metastases not requiring steroids were enrolled. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), depth of response (DepOR), overall survival (OS) and safety. Response endpoints were assessed in full analysis set (NCT02981108). Results: From May 2018 to October 2018, 244 patients entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients). Of 88 patients with CNS metastases on baseline brain scans, 23 had at least one intracranial measurable target lesion. At cutoff date (Aug 1, 2019), the median duration of follow-up for progression-free survival was 11.8 months. 168 of 244 patients achieved confirmed partial responses. The ORR was 68.9% (95% CI: 62.6, 74.6). The DCR was 93.4% (95% CI: 89.6, 96.2). The mPFS (48.0% maturity) and mDOR were 12.3 (95% CI: 9.6, 13.8) and 12.4 (95% CI: 11.3, NA) months, respectively. The confirmed CNS ORR and DCR were 60.9% (95% CI: 38.5, 80.3) and 91.3% (95% CI: 72.0, 98.9), respectively. The CNS mPFS (47.8% maturity) was 10.8 (95% CI: 5.5, 12.6) months. The safety profile was consistent with the previous report. The most common grade 3 and 4 adverse reactions were increased blood creatine phosphokinase (17 [7.0%]) and pulmonary embolism (6 [2.5%]). There was no interstitial lung disease reported. Conclusions: Almonertinib demonstrated progression-free survival benefit in EGFR T790M positive NSCLC patients who had progressed after previous EGFR-TKI treatment, especially showed clinically meaningful efficacy against CNS metastases, and the safety profile was consistent with that reported previously. A randomized, controlled, double-blinded, phase III study is ongoing comparing almonertinib with gefinitib in first-line treatment of advanced NSCLC patients.

Citation Format: Shun Lu, Qiming Wang, Guojun Zhang, Xiaorong Dong, Cheng-Ta Yang, Yong Song, Gee-Chen Chang, You Lu, Hongming Pan, Chao-Hua Chiu, Zhehai Wang, Jifeng Feng, Jianying Zhou, Xingxiang Xu, Renhua Guo, Jianhua Chen, Haihua Yang, Yuan Chen, Zhuang Yu, Her-Shyong Shiah, Chin-Chou Wang, Nong Yang, Jian Fang, Ping Wang, Kai Wang, Yanping Hu, Jianxing He, Ziping Wang, Jianhua Shi, Shaoshui Chen, Qiong Wu, Changan Sun, Chuan Li, Hongying Wei, Ying Cheng, Wu-Chou Su, Te-Chun Hsia, Jiuwei Cui, Yuping Sun, James Chih-Hsin Yang. A multicenter, open-label, single-arm, phase II study: The third generation EGFR tyrosine kinase inhibitor almonertinib for pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (APOLLO) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT190.