Dalmelitinib Plus Aumolertinib Shows Durable Activity in MET-Amplified, EGFR-Mutant NSCLC After Progression

April 2, 2026 | Caroline Seymour

The combination of dalmelitinib (HS-10241) and aumolertinib demonstrated clinically meaningful and durable activity in patients with EGFR-mutant and MET-amplified advanced non–small cell lung cancer (NSCLC) and manageable toxicity, according to data from the dose-expansion portion of the phase 1b HS-10241-102 trial (NCT05430386).¹

In results shared during the 2026 European Lung Cancer Congress, patients who had received any prior EGFR TKI (n = 115) achieved a confirmed objective response rate (ORR) of 48.7% (95% CI, 39.3%-58.2%), a median progression-free survival (PFS) of 7.4 months (95% CI, 5.6-10.1), and a median overall survival (OS) of 25.4 months (95% CI, 18.9-27.8). At a median follow-up of 18.9 months, the median duration of response (DOR) was 11.1 months (95% CI, 7.5-16.7) and the disease control rate (DCR) was 84.3% (95% CI, 76.4%-90.5%).

Among patients who received only a third-generation EGFR (n = 100), the confirmed ORR was 47.0% (95% CI, 36.9%-57.2%). The median PFS was 7.3 months (95% CI, 5.5-9.3), and the median OS was 22.9 months (18.4-26.6). The median DOR was 10.4 months (95% CI, 5.6-13.5) and the DCR was 82.0% (95% CI, 73.1%-89.0%).

Among patients who received only a first- or second-generation EGFR (n = 15), the confirmed ORR was 60.0% (95% CI, 32.3%-83.7%). The median DOR was 21.9 months (95% CI, 3.3-not reached [NR]) and the DCR was 100.0% (95% CI, 78.2%-100.0%). The median PFS was 17.3 months (95% CI, 5.5-25.7), and the median OS was not reached (95% CI, 12.6-NR).

“The combination of dalmelitinib and aumolertinib demonstrated promising efficacy in patients with EGFR-mutant, MET-amplified advanced NSCLC who had progressed after prior EGFR TKI therapy,” Xiaorong Dong, MD, PhD, and coauthors, shared in a poster during the meeting. Dong is a professor at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China.

What is the unmet clinical need the study sought to address?

Disease progression following acquired resistance is common in patients with EGFR-mutant NSCLC who receive up-front therapy with an EGFR TKI. Receipt of a third-generation EGFR TKI is commonly associated with subsequent MET amplification, allowing dual inhibition of c-MET and EGFR to be studied as a potential means of overcoming this resistance pathway.

Dalmelitinib is a highly selective, oral MET TKI, that served as the c-MET inhibitor of choice, alongside the third-generation EGFR TKI aumolertinib in the open-label, phase 1b HS-10241-102 trial. The study evaluated the activity and safety of the regimen in Chinese patients with MET-positive, EGFR-mutant NSCLC.

To be eligible, patients had to have received a diagnosis of advanced, EGFR-mutant and MET-amplified NSCLC with measurable disease per RECIST 1.1 and an ECOG performance status of 0 or 1. Confirmed c-MET status required a MET copy number of at least 5 or a MET/CEP7 ratio of 2 or greater on fluorescence in situ hybridization; or MET 3+ on at least 50% of tumor cells per immunohistochemistry.

What was the study design?

Eligible patients received 300 mg of oral dalmelitinib twice daily plus 110 mg of oral aumolertinib once daily.

The primary end point was objective response rate (ORR) per RECIST 1.1. Secondary end points included duration of response, disease control rate, and progression-free survival per RECIST 1.1, overall survival, safety, and pharmacokinetic measures.

Prior findings presented at the 2023 ASCO Annual Meeting indicated that the combination produced an ORR of 61.5% in patients with MET-amplified NSCLC following treatment with an EGFR TKI (n = 45).²

As part of the dose-expansion analysis, all patients who received at least 1 dose of the study regimen were included in the safety analysis set. The efficacy evaluable analysis set included all patients who had received at least 1 dose of the regimen and had baseline and at least 1 post baseline tumor response evaluation.

The data cutoff date for the present analysis was July 31, 2025, at which point 132 patients from the dose-expansion portion had received at least 1 dose of study treatment.

“Of 132 patients, 109 patients [82.6%] received third-generation EGFR TKIs; 16 patients [12.1%] received first- or second-generation EGFR TKIs only and were EGFR T790M negative; another 7 patients [5.3%] were treatment naive or received first- or second-generation EGFR TKIs and were EGFR T790M positive,” Dong said.

What were the patient characteristics?

Among all patients (n = 132), the median age was 59.0 years (range, 35-82) and most patients were female (56.1%). Clinical stage at screening was either III (3.0%), IV (96.2%) or undeterminable (0.8%). Pathological diagnosis was predominantly that of adenocarcinoma (93.9%), followed by other or unknown (3.0%), squamous (1.5%), and adenosquamous carcinoma (1.5%). Most patients had an ECOG performance status of 1 (77.3%) and had received either 1 (47.0%) or 2 (35.6%) prior lines of therapy; 17 (12.9%) had received 3 or more and 6 (4.5%) had no prior history of antitumor therapy or had received only adjuvant therapy. Prior therapy included chemotherapy (32.6%) and EGFR TKI therapy (97.0%). MET gene copy number was at least 5 in most patients (98.5%), with 1 each falling below the threshold or having an unknown value.

What was the safety profile in the pretreated population?

“The safety profile was manageable with reversible adverse effects [AEs], and no new safety signals were identified,” Dong explained.

Treatment-emergent adverse effects (TEAEs) occurred in 99.2% of patients (n = 132), 67.4% of which were grade 3 or greater. TEAEs leading to dose reduction or discontinuation occurred in 36.4% and 6.8% of patients, respectively. Common grade 3 or greater TEAEs that occurred in at least 15% of patients were increased gamma-glutamyl transferase levels (15.9%), and increased alanine aminotransferase (15.9%) and aspartate aminotransferase (15.2%) levels.

Dong shared that MET-related AEs including peripheral edema and hypoproteinemia were generally mild with no grade 3 or higher effects reported.

What is the significance of these data? What are the next steps for the regimen?

“These findings demonstrated encouraging clinical activity in a heavily pretreated population, where over 85% of efficacy-evaluable patients had received prior third-generation EGFR TKI therapy. Notably, this study enrolled patients with a broader MET amplification threshold compared with previously reported studies,” Dong said.

The combination is under further evaluation in a randomized phase 3 trial, for which results will be forthcoming.

Disclosures: Dong declared no conflicts of interest.

References

Dong X, Yu Y, Chen J, et al. Dalmelitinib (HS-10241) combined with aumolertinib in EGFR-TKIs-pretreated patients with EGFR-mutant and MET-amplified advanced NSCLC: a phase 1b study. Presented at: 2026 European Lung Cancer Congress; March 25-28, 2026; Copenhagen, Denmark. Abstract 31P.

Dong X, Chen J, Yu Y, et al. Phase 1b study of HS-10241 combined with almonertinib in pre-treated advanced non-small cell lung cancer (NSCLC) harboring EGFR mutation. J Clin Oncol. 2023;41(16):e21134. doi:10.1200/JCO.2023.41.16_suppl.e21134