Dalmelitinib Plus Aumolertinib in Advanced NSCLC Patients With EGFR-TKI Resistance and MET Amplification: A Randomized Phase 3 Trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: PURPOSE MET amplification accounts for up to 30% of acquired resistance to EGFR-TKI, especially following third-generation EGFR-TKI treatment, yet precision-targeted therapeutic options remain limited. Early-phase studies demonstrated promising antitumor activity with the MET-TKI dalmelitinib combined with the third-generation EGFR-TKI aumolertinib. This phase 3 trial compared dalmelitinib-aumolertinib with platinum-based chemotherapy in EGFR -mutated, MET -amplified advanced NSCLC after EGFR-TKIs progression. PATIENTS AND METHODS This randomized, open-label, phase 3 trial ( NCT06110663 ) enrolled patients with locally advanced or metastatic EGFR -mutated, MET -amplified NSCLC after EGFR-TKI progression. MET amplification was defined by fluorescence in situ hybridization as a mean MET copy number ≥5 or MET / CEP7 ratio ≥2. Patients were randomly assigned (1:1) to dalmelitinib-aumolertinib or platinum-based chemotherapy groups. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review per RECIST 1.1. Secondary endpoints included overall survival, objective response rate (ORR), duration of response (DoR), and safety. RESULTS A total of 314 enrolled patients were assigned to dalmelitinib-aumolertinib (n=156) or platinum-based chemotherapy (n=158). Median follow-up was 11.2 months at the data cutoff date (December 10, 2025). Median PFS was 6.2 months with dalmelitinib-aumolertinib and 4.4 months with chemotherapy (HR, 0.60; 95% CI, 0.45 to 0.81; P <0.001). Corresponding ORRs were 59.6% and 38.6%, and median DoRs were 9.7 months and 4.4 months, respectively. Overall survival data were immature. Grade ≥3 treatment-emergent adverse events occurred in 50.0% and 51.0% of patients, respectively. Toxicity profiles differed, with more hepatic laboratory abnormalities with dalmelitinib-aumolertinib and more hematologic toxicities with chemotherapy. CONCLUSION The dalmelitinib-aumolertinib combination significantly improved PFS versus chemotherapy, with a manageable safety profile in advanced EGFR -mutated, MET -amplified NSCLC after progression on EGFR-TKI. These findings support dual EGFR/ MET inhibition as a new treatment option in this biomarker selected population.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-26-02432
Authors: Ziming Li, Xiaorong Dong, Yan Yu, Wenxiu Yao, Yongzhong Luo, Xiangjiao Meng, Xinmin Yu, Jie Hu, Lin Wu, Longhua Sun, Zhangzhou Huang, Dongqing Lv, Chunling Liu, Zhenyong Zhang, Xingya Li, Yongchang Zhang, Lixia Ma, Jianhua Shi, Ting Wei, Shujun Li, Lisi Ma, Wenzhao Qin, Congmao Wang, Xiaoqing Zhang, Shun Lu
Institutions: Shanghai Jiao Tong University, Shanghai Chest Hospital, Wuhan Union Hospital, Huazhong University of Science and Technology, Third Affiliated Hospital of Harbin Medical University, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, Central South University, Hunan Cancer Hospital, Shandong Tumor Hospital, Shandong First Medical University, Zhejiang Cancer Hospital, Shanghai Medical College of Fudan University, Fudan University, Zhongshan Hospital, First Affiliated Hospital of Nanchang University, Fujian Medical University, Fujian Provincial Cancer Hospital, Zhejiang Taizhou Hospital, Xinjiang Medical University, Tumor Hospital of Xinjiang Medical University, Sheng Jing Hospital, First Affiliated Hospital of Zhengzhou University, Jilin Province Tumor Hospital, Hansoh Pharma (China), Zhujiang Hospital, Southern Medical University, Guangdong Medical College
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7223659902