Dalmelitinib Plus Aumolertinib Prolongs PFS in EGFR-Mutated, MET-Amplified NSCLC

Dalmelitinib plus aumolertinib prolonged progression-free survival (PFS) vs platinum-based chemotherapy in EGFR-mutated, MET-amplified advanced non-small cell lung cancer (NSCLC) that progressed on EGFR tyrosine kinase inhibitor (TKI) therapy, according to a phase 3 trial published online as an accepted manuscript in the Journal of Clinical Oncology.

MET amplification underlies as many as 30% of cases of acquired resistance to EGFR-TKIs, the investigators noted. Dalmelitinib is an investigational, highly selective MET-TKI; aumolertinib is a third-generation EGFR-TKI approved in China.

The open-label trial (NCT06110663) randomly assigned 314 patients at 48 centers in China to dalmelitinib 300mg twice daily plus aumolertinib 110mg once daily (n=156) or pemetrexed-platinum chemotherapy (n=158). All had EGFR exon 19 deletion or L858R mutations and MET amplification confirmed centrally by fluorescence in situ hybridization (mean MET copy number ≥5 or MET-to-chromosome 7 centromere ratio ≥2); 94.3% had received a third-generation EGFR-TKI. After a median follow-up of 11.2 months, median PFS by blinded independent central review, the primary endpoint, was 6.2 months with the combination vs 4.4 months with chemotherapy (hazard ratio, 0.60; 95% CI, 0.45-0.81).

Objective response rates were 59.6% vs 38.6%. Median PFS was longer with the combination in subgroups with MET copy number ≥10 and 5 to <10. Overall survival (OS) data were immature, with little separation between groups; 46.8% of the chemotherapy group crossed over to the combination.

Grade ≥3 treatment-emergent adverse events occurred in 50.0% vs 51.0% of patients, with more hepatic laboratory abnormalities with the combination and more hematologic toxicity with chemotherapy. Serious adverse events (37.8% vs 24.8%) and discontinuations due to adverse events (7.7% vs 2.8%) were more frequent with the combination. One of two fatal adverse events in the combination group was subacute hepatic failure.

The investigators concluded that the results indicate that dual EGFR/MET inhibition is a new therapeutic option for patients selected by this biomarker. They noted the open-label design and immature OS data, and that benefit in patients with MET overexpression remains undetermined.

Source: Li Z, Dong X, Yu Y, et al. Dalmelitinib plus aumolertinib in advanced NSCLC patients with EGFR-TKI resistance and MET amplification: a randomized phase 3 trial. J Clin Oncol. Published online October 26, 2026. doi:10.1200/JCO-26-02432