Ensartinib for advanced or metastatic non-small-cell lung cancer with MET exon 14 skipping mutations (EMBRACE) a multi-center, single-arm, phase 2 trial
机构:[1]Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China[2]Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China[3]Department of Pulmonary and Critical Care Medicine, Lung Cancer Center/Lung Cancer Institute, West China Hospital of Sichuan University, Chengdu, Sichuan, China四川大学华西医院[4]Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China[5]Hubei Province Key Laboratory of Biological Targeted Therapy, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China华中科技大学同济医学院附属协和医院[6]Second Oncology Department, Handan Central Hospital, Handan, Hebei, China[7]Department of Pathology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China[8]Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China[9]Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Background MET exon14 skipping mutations (METex14) is an established actionable driver oncogene of non-small- cell lung cancer (NSCLC). While ensartinib is a known second-generation tyrosine kinase inhibitor with primary activity against ALK translocation, it is also classified as a type Ia MET inhibitor. We have previously shown antitumor activity against METex14 positive NSCLC both in vivo and in vitro. The EMBRACE trial aims to evaluate the clinical efficacy and safety of ensartinib for treatment of METex14 positive NSCLC. Methods This is a multicenter single arm phase II investigator-initiated study that enrolled METex14 positive lung cancer after failing first line chemotherapy and/or immunotherapy. Eligible patients received ensartinib 225 mg orally once daily in a continuous 28-day treatment cycle until disease progression, unacceptable side effect, or death. Primary endpoint was investigator-assessed objective response rate (ORR), and the secondary end point included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR) and safety profiles. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2100048767). Findings From July 2021 to February 2024, a total of 31 patients were enrolled and received ensartinib. Median followup time of the 30 evaluable patients was 9.2 months (95% Confidence Interval [CI], 6.3-not estimable). The ORR was 53.3% (16/30; 95% CI, 35.5-71.2) and DCR was 86.7% (26/30; 95% CI, 74.5-98.8). Median PFS was 6.0 months (95% CI, 3.0-8.8) and median DoR was 7.9 months (95% CI, 4.8-8.7). Adverse events (AEs) were reported in 24 patients (80%), with 7 (23.3%) of grade 3. The most common AEs were rash (14/30, 46.7%), followed by anemia (7/30, 23.3%), increased ALT (7/30, 23.3%), increased AST (7/30, 23.3%), and pruritus (6/30, 20%). No serious adverse events or treatment-related deaths occurred. Importantly, the exploratory ctDNA analysis indicates that clearance of circulating tumor DNA (ctDNA) at four weeks treatment was associated with more favorable treatment outcomes comparing with patients having positive ctDNA. Interpretation Ensartinib has a promising anti-tumor activity and manageable safety in previously treated patients with METex14 positive lung cancer. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
基金:
National Natural Science Foundation of China [82422001, 82370028, Y-2022METAZMS-0066]
第一作者机构:[1]Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China[2]Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China[*1]Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310052, China
共同第一作者:
通讯作者:
通讯机构:[1]Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China[2]Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China[9]Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA[*1]Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310052, China[*2]Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
推荐引用方式(GB/T 7714):
Xia Yang,Tian Panwen,Zhou Mo,et al.Ensartinib for advanced or metastatic non-small-cell lung cancer with MET exon 14 skipping mutations (EMBRACE) a multi-center, single-arm, phase 2 trial[J].ECLINICALMEDICINE.2025,81:doi:10.1016/j.eclinm.2025.103099.
APA:
Xia, Yang,Tian, Panwen,Zhou, Mo,Zhao, Jun,Jin, Yang...&Li, Wen.(2025).Ensartinib for advanced or metastatic non-small-cell lung cancer with MET exon 14 skipping mutations (EMBRACE) a multi-center, single-arm, phase 2 trial.ECLINICALMEDICINE,81,
MLA:
Xia, Yang,et al."Ensartinib for advanced or metastatic non-small-cell lung cancer with MET exon 14 skipping mutations (EMBRACE) a multi-center, single-arm, phase 2 trial".ECLINICALMEDICINE 81.(2025)