Safety, Efficacy, and Biomarker Analysis of Deulorlatinib (TGRX-326) in Anaplastic Lymphoma Kinase-Positive NSCLC: A Multicenter, Open-Label, Phase 1/1b Trial

作者：Shen Zhao, Huaqiang Zhou, Nong Yang, Zhehai Wang, Wenjian Jin, Yuxiang Ma, Jinhui Xue, Xingya Li, Yunpeng Liu, Rui Meng, Jianying Zhou, Ying Cheng, Yongsheng Wang, Zhuang Yu, Yu Cao, Yuanyuan Zhao, Yan Huang, Wenfeng Fang, Yang Zhang, Shaodong Hong, Bo Wu, Yan-Xia Shi, Jingrong Cao, Mingyan Xu, Xiaoni Zhang, Longyu Hu, Bo Peng, Yunpeng Yang, Li Zhang, Hongyun Zhao · 发表于：Journal of Thoracic Oncology · 年份：2024 · DOI：10.1016/j.jtho.2024.11.010 · 被引用次数：8 · 研究领域：Lung Cancer Treatments and Mutations、Lymphoma Diagnosis and Treatment、Lung Cancer Research Studies

INTRODUCTION: Patients with anaplastic lymphoma kinase (ALK)-positive NSCLC developing resistance to second-generation inhibitors have limited treatment options. Deulorlatinib is a highly brain-penetrant, new-generation ALK/ROS1 inhibitor. We evaluated the safety, efficacy, and pharmacokinetics of deulorlatinib in ALK-positive NSCLC. METHODS: This three-part (dose-escalation/dose-expansion/cohort-expansion), open-label, phase 1/1b trial was conducted at 22 sites in the People's Republic of China (ClinicalTrials.gov, NCT05441956). Patients who were eligible had advanced ALK/ROS1-positive NSCLC. Patients enrolled in dose-escalation/dose-expansion parts were previously treated with one or more second-generation ALK inhibitors (ALK-positive) or crizotinib (ROS1-positive) and received deulorlatinib 5 to 125 mg once per day. Patients enrolled in cohort-expansion parts were either crizotinib-treated, second-generation tyrosine kinase inhibitor (TKI)-treated, or TKI-naïve; and received deulorlatinib at the recommended phase 2 dose (RP2D). The primary outcomes were safety and tolerability. Here, we report safety analysis in all patients and efficacy analysis in patients who were ALK-positive. RESULTS: Between April 2021 and March 2023, 198 patients were enrolled (ALK-positive = 171, ROS1-positive = 27). The most common treatment-related adverse events (TRAEs) were hypercholesterolemia (79.3%), hypertriglyceridemia (77.3%), and weight gain (53.0%). 40.4% of patients had grade 3 or high...