Safety, pharmacokinetic, pharmacodynamic, and efficacy properties of orally administered APG-2449 in patients with advanced ALK and ROS1 non-small-cell lung cancer: a multicentre, open-label, single-arm phase 1 trial

作者：Yu‐Xiang Ma, Zhengbo Song, Jianhua Chen, Yanqiu Zhao, Wenfeng Fang, Yubiao Guo, Yugang Dong, Yun-Peng Yang, Gang Wu, Jian Fang, Xiaoyan Lin, Jundong Li, Yan Huang, Yuanyuan Zhao, Shaodong Hong, Jinhui Xue, Yang Zhang, Qianwen Liu, Chen Yang, Xu Liang, Yun Yang, Dengkun Xiong, Dajun Yang, Yifan Zhai, Li Zhang, Hongyun Zhao · 发表于：EClinicalMedicine · 年份：2025 · DOI：10.1016/j.eclinm.2025.103556 · 被引用次数：2 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies

APG-2449 is a focal adhesion kinase (FAK) inhibitor and a third-generation anaplastic lymphoma kinase (ALK)-proto-oncogene receptor tyrosine kinase ROS (ROS1) tyrosine kinase inhibitor (TKI). The aim of this first-in-human study was to evaluate safety and efficacy of APG-2449 in patients with advanced non-small-cell lung cancer (NSCLC). This single-arm, multicentre, phase 1 clinical trial included a dose escalation to determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), followed by a dose-expansion stage at RP2D to evaluate safety. Secondary endpoints included pharmacokinetics, pharmacodynamics, and preliminary efficacy. APG-2449 was administered once daily in 28-day cycles through a 3 + 3 dose escalation. Eligible patients were aged 18 years or older and had advanced ALK or ROS1 fusion gene–positive NSCLC and other solid tumours (during the dose escalation). Patients with ALK -positive or ROS1 -positive NSCLC regardless of previous TKI treatment were enrolled during the dose escalation. After RP2D was determined, patients with second-generation TKI-treated ALK + NSCLC, TKI-naïve ALK + , and TKI-naïve or TKI-treated ROS1 + NSCLC were enrolled in dose expansion. Eligible patients also had: (1) an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 1 or less; (2) adequate bone marrow reserve and organ function; and (3) no or stable brain metastases. This study was registered with ClinicalTrials.gov ( NCT03917043 ). Recruitment is ongo...