Efficacy, safety and dose selection of AZD3759 in patients with untreated EGFR-mutated non-small-cell lung cancer and central nervous system metastases in China (CTONG1702-Arm 8): a multi-center, single-arm, phase 2 trial

• Published in: EClinicalMedicine Vol. 64; p. 102238
• Main Authors: Maggie Liu, Si-Yang, Dong, Xiao-Rong, Wang, Zhen, Du, Yingying, Cui, Jiu-Wei, Chu, Qian, Xu, Bing-Fei, Zheng, Ming-Ying, Deng, Jia-Yi, Lu, Chang, Wei, Xue-Wu, Li, Yang-Si, Zheng, Mei-Mei, Yang, Ming-Yi, Huang, Jie, Li, Anna, Bai, Xiao-Yan, Sun, Yue-Li, Xu, Chong-Rui, Wang, Bin-Chao, Chen, Hua-Jun, Yang, Jin-Ji, Yan, Hong-Hong, Zhong, Wen-Zhao, Zhou, Qing, Wu, Yi-Long
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2023; Elsevier
• Subjects: AZD3759; CNS metastasis; EGFR mutation; First-line setting; Internal Medicine; Lung cancer; EGFR mutation; CNS metastasis; AZD3759; Lung cancer; First-line setting
• ISSN: 2589-5370; 2589-5370
• DOI: 10.1016/j.eclinm.2023.102238

Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon’s minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts. Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively. AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option. Chinese Thoracic Oncology Group (CTONG).