DOI: 10.1200/jco-26-02432 ISSN: 0732-183X

Dalmelitinib Plus Aumolertinib in Advanced NSCLC Patients With EGFR-TKI Resistance and MET Amplification: A Randomized Phase 3 Trial

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
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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.

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