Top KOLs Discussing Dalmelitinib + Aumolertinib (HS-10241-301)
Dalmelitinib + Aumolertinib (HS-10241-301) Key Slides
ESMO 2026 slides
| Dalmelitinib + aumolertinib (n=156) | Platinum-pemetrexed (n=158) | HR (95% CI) | |
|---|---|---|---|
| Median PFS, months | 6.2 | 4.4 | 0.601 (0.448–0.805), P < 0.001 (primary-analysis slide; abstract) |
| Events, n (%) | 92 (59.0) | 105 (66.5) | Unstratified 0.568 (0.426–0.759) (subgroup forest plot, FAS row) |
| Median follow-up, months | 11.4 | 10.7 | — |
| Dalmelitinib + aumolertinib (n=156) | Platinum-pemetrexed (n=158) | Unstratified HR (95% CI) | |
|---|---|---|---|
| Median OS, months (95% CI) | Not reached (17.5–NE) | 19.6 (14.6–NE) | 0.840 (0.524–1.346) |
| Subsequent MET inhibitor in the chemotherapy arm | — | 82 (51.9%): 74 study crossover, 8 other MET inhibitors | — |
Same or overlapping slides also posted by @HHorinouchi, @Dr_Oncologista.
What physicians are debating
Which MET definition?
The trial selected MET amplification by FISH (copy number ≥5 or MET/CEP7 ratio ≥2), a lower threshold than SAFFRON (FISH ≥10 and/or IHC 3+ ≥90%). Only 33% of patients had copy number ≥10, vs 71–72% in SACHI and SAFFRON, per Rebecca Heist’s comparison slide. The unstratified PFS HR was 0.485 at copy number ≥10 and 0.618 at ≥5 to <10 (exploratory). Adam Januszewski, MD, noted that MET amplification “accounts for ~10–15% (definition-dependent).”
Invited discussant slides (Rebecca S. Heist, ESMO 2026) · 2615O presentation slides (Ziming Li, ESMO 2026)Rebiopsy and testing at progression
Heist’s takeaway was that “MET at time of progression is an actionable biomarker & requires testing.” Januszewski wrote that the trial “Reinforces importance of rebiopsy at progression”. Patients were selected on post-progression tissue biopsy confirmed by a central lab.
Invited discussant slides (Rebecca S. Heist, ESMO 2026)OS immature, with heavy crossover
OS (unstratified HR 0.840, 0.524–1.346) is immature, and 51.9% of the chemotherapy arm went on to a MET inhibitor (46.8% by study crossover). Stephen Liu, MD, wrote “OS immature and high crossover”; Aya Mohamed, MD, noted “OS remains immature.”
2615O presentation slides (Ziming Li, ESMO 2026)Liver toxicity and discontinuation
Grade ≥3 event rates were similar between arms, but the profiles differed, with liver-enzyme elevations on the combination and hematologic toxicity on chemotherapy. Liu noted “Higher d/c rate with TKIs” (7.1% vs 2.8% for treatment-related events), and Mohamed described “distinct hepatic vs hematologic toxicities.”
2615O presentation slides (Ziming Li, ESMO 2026)MET inhibitor combinations vs amivantamab
Tom John, MD, summarized Heist’s discussion: “In MET acquired resistance to EGFR TKI, MET inhibition is better than chemotherapy. What about bispecific antibodies? Not so clear.” Heist set this trial beside SACHI and SAFFRON; amivantamab plus chemotherapy (MARIPOSA-2) is approved after an EGFR TKI without MET selection. First-line MET-directed combinations were tested separately in SANOVO.
Invited discussant slides (Rebecca S. Heist, ESMO 2026) · FDA: amivantamab + carboplatin-pemetrexed approval, Sep 2024Physician reactions to Dalmelitinib + Aumolertinib (HS-10241-301)
In EGFR-mutant,MET-positive NSCLC after EGFR-TKI progression, dalmelitinib + aumolertinib improved PFS vs platinum/pemetrexed (6.2 vs 4.4 months; HR 0.60, p<0.001) ORR was 59.6% vs 38.6%,with distinct hepatic vs hematologic toxicities. OS remains immature. 🫁 @OncoAlert #ESMO26 https://t.co/7ui1zoKnj1
Excellent discussion from Dr Heist. In MET acquired resistance to EGFR TKI, MET inhibition is better than chemotherapy. What about bispecific antibodies? Not so clear. #LCSM #ESMO26 https://t.co/OYRggGz1f0
ESMO 2026: Exciting phase 3 data from Prof. Ziming Li reveals a promising new chemo-free option for EGFR-m, MET-amplified NSCLC after EGFR-TKI failure. Dalmelitinib + Aumolertinib vs. Chemotherapy shows major benefits: 📊 40% lower risk of progression or death (HR=0.601, p<0.001) ⏱️ mPFS: 6.2 vs. 4.4 months 📈 ORR: 59.6% vs. 38.6% ⏳ mDoR: 9.7 vs. 4.4 months Benefits were consistent across all pre-defined subgroups, and safety remains manageable with mostly grade 1-2 events. #ESMO2026 #LungCancer #LCSM #Oncology #CancerResearch
🚨 #ESMO26 Another Ph3 study reinforcing MET amp as a key target in EGFRm NSCLC! Dalmelitinib + aumolertinib vs chemo post-EGFR TKI: 📈 PFS 6.2 vs 4.4m (HR 0.60) 🔬 Reinforces importance of rebiopsy at progression, MET-amp accounts for ~10–15% (definition-dependent).
#ESMO26 Dr. Ziming Li with phase III study of dalmelitinib + aumolertinib vs platinum chemo in EGFR+ NSCLC with MET amp post EGFR TKI. PFS favors TKIs: 6.2m vs 4.4m, HR 0.60; OS immature and high crossover (HR 0.84). RR 60% vs 39%. Higher d/c rate with TKIs. #ESMOAmbassadors https://t.co/PWgI5JGNLY
🆙#ESMO26 Proffered Paper II: #LCSM Mets 🔥Dalmelitinib Plus Aumolertinib Versus Platinum-Based Chemotherapy in Advanced NSCLC Patients With MET Amplification Post EGFR TKI: A Randomized, Phase 3 Study 🎙️Dr. Ziming Li 🔢2615O 🎯Met Primary Endpoint 🎯IRC-PFS 6.2 vs 4.4mo (HR 0.601, p<0.001; n=314) 🎯ORR 59.6% vs 38.6% 🎯OS HR 0.840 (Immature, 46.8% Crossover) 🎯Grade≥3 TEAEs 50.0% vs 51.0% ☑️NCT06110663 🔗 https://t.co/M4ccE0iSMW @OncoAlert @Larvol @myESMO @IASLC @EGFRResisters
🆙 #ESMO26 Proffered Paper II: #LCSM Mets 🔥Dalmelitinib Plus Aumolertinib Versus Platinum-Based Chemotherapy in Advanced NSCLC Patients With MET Amplification Post EGFR TKI 🎙️Dr. Ziming Li 🔢2615O ☑️NCT06110663 🔗 https://t.co/M4ccE0iSMW @OncoAlert @Larvol @myESMO @IASLC @EGFRResisters
Posted September 23, before the results were presented.
Dalmelitinib + Aumolertinib (HS-10241-301) Trial Design
HS-10241-301 asked whether dalmelitinib (HS-10241), an oral MET tyrosine kinase inhibitor, combined with the third-generation EGFR TKI aumolertinib improves progression-free survival over platinum-pemetrexed when EGFR-mutant NSCLC acquires MET amplification after an EGFR TKI. The trial has no separate acronym; the presenter’s slides use the protocol number. It is sponsored and funded by Jiangsu Hansoh Pharmaceutical.
Study Design
Randomized 1:1, open-label, multicenter phase 3 in China (NCT06110663, HS-10241-301). 314 randomized (156 vs 158). Stratified by prior third-generation EGFR TKI, baseline brain metastases and MET/CEP7 ratio (≥2 vs <2). Chemotherapy patients could switch to the combination after BICR-assessed progression.
Population
Advanced EGFR-mutant NSCLC with progression on or intolerance of an EGFR TKI; MET amplification by FISH (copy number ≥5 or MET/CEP7 ratio ≥2) confirmed by a central lab; ECOG PS 0–1. 94.3% had a prior third-generation EGFR TKI.
Interventions
Dalmelitinib 300 mg twice daily plus aumolertinib 110 mg once daily, vs cisplatin 75 mg/m² or carboplatin AUC 5 plus pemetrexed 500 mg/m² for 4–6 cycles, then pemetrexed maintenance.
Endpoints
Primary: PFS by blinded independent central review (BICR). Secondary: ORR, DCR and DoR by BICR, OS, adverse events.
Presenter & Discussant
Presenter: Ziming Li, MD (Shanghai Chest Hospital), co-first author of the JCO paper. Senior author: Shun Lu, MD, PhD. Invited discussant (LBA69 and 2615O): Rebecca S. Heist, MD (Massachusetts General Hospital).
Data Cut
Data cutoff December 10, 2025; final PFS analysis preplanned at 197 events (92 + 105 observed). Median follow-up 11.2 months.
Dalmelitinib + Aumolertinib (HS-10241-301) in the News
Dalmelitinib + Aumolertinib (HS-10241-301) Questions
What is the dalmelitinib plus aumolertinib phase 3 trial?
HS-10241-301 (NCT06110663) is a randomized, open-label phase 3 trial in China, sponsored by Jiangsu Hansoh Pharmaceutical, comparing dalmelitinib (a MET tyrosine kinase inhibitor) plus aumolertinib (a third-generation EGFR TKI) with platinum-pemetrexed in 314 patients with EGFR-mutant advanced NSCLC with MET amplification (FISH copy number ≥5 or MET/CEP7 ratio ≥2) after progression on or intolerance of an EGFR TKI. It has no separate trial acronym.
What did it show at ESMO 2026?
At the final PFS analysis (data cutoff December 10, 2025), median PFS by blinded independent central review, the primary endpoint, was 6.2 vs 4.4 months, HR 0.601 (95% CI 0.448–0.805), P < 0.001. ORR was 59.6% vs 38.6%. OS was immature, unstratified HR 0.840 (0.524–1.346), and 46.8% of the chemotherapy arm crossed over.
Why are there two PFS hazard ratios, 0.601 and 0.568?
0.601 (95% CI 0.448–0.805) is the HR from the primary analysis, printed on the primary-endpoint slide and in the abstract (the JCO paper rounds it to 0.60, 0.45–0.81). 0.568 (0.426–0.759) is the unstratified HR for the full analysis set, printed as the first row of the subgroup forest plot. The primary result is 0.601.
Is dalmelitinib approved?
No. Dalmelitinib is investigational. Hansoh reported that China’s NMPA accepted a new drug application for dalmelitinib plus aumolertinib in February 2026 for EGFR-mutant NSCLC with MET amplification after EGFR-TKI therapy. Aumolertinib (Ameile in China, Aumseqa elsewhere) is approved in China and, as monotherapy, in the EU (February 2026); it is not FDA approved.
How does it compare with SAFFRON and SACHI?
The discussant, Rebecca Heist, MD, placed it beside SACHI and SAFFRON (osimertinib plus savolitinib) as phase 3 support for combined EGFR and MET inhibition after an EGFR TKI. The trials differ in MET definitions, prior third-generation TKI exposure (94.3% here) and crossover, so the numbers are not directly comparable. See SAFFRON.