WCLC 2025 - Posters & ePosters-P3.12.48 Efficacy and Safety of Savolitinib in Advanced or Metastatic METex14 NSCLC Patients With or Without Prior Immunotherapy

P3.12.48 Efficacy and Safety of Savolitinib in Advanced or Metastatic METex14 NSCLC Patients With or Without Prior Immunotherapy

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This phase 3b single-arm study evaluated the efficacy and safety of savolitinib (a selective oral MET inhibitor) in advanced or metastatic MET exon 14 skipping mutation (METex14) non-small cell lung cancer (NSCLC) patients who were previously treated, comparing those with prior immunotherapy (prior IO) to IO-naïve patients. The study enrolled 79 previously treated patients: 19 with prior IO and 60 without.<br /><br />Baseline characteristics were generally similar, though the prior IO group had a slightly higher incidence of brain metastases. Savolitinib was administered daily at 600 mg or 400 mg based on body weight.<br /><br />Efficacy outcomes showed the prior IO-naïve group had better results: independent review committee (IRC)-assessed overall response rate (ORR) was 45.0% vs. 31.6% in the prior IO group; disease control rates (DCR) were 91.7% vs. 94.7%, median progression-free survival (mPFS) was 13.7 vs. 9.7 months, and median overall survival (mOS) was 25.3 vs. 18.0 months. Duration of response was similar across groups (~11 months). These differences suggest a trend toward improved efficacy in IO-naïve patients, although sample size imbalance and baseline differences limit firm conclusions.<br /><br />Regarding safety, the prior IO group experienced higher rates of grade 3 treatment-related adverse events (TRAEs) (63.2% vs. 51.7%), more TRAEs leading to dose interruptions/reductions (89.5% vs. 60.0%), and more TRAEs causing treatment discontinuation (15.8% vs. 5.0%), indicating potentially better tolerability in IO-naïve patients.<br /><br />These findings position savolitinib as a robust MET-TKI option alongside agents like tepotinib and capmatinib. The impact of prior immunotherapy on MET-TKI efficacy and safety requires further investigation. The study was funded by HUTCHMED and AstraZeneca and involved multiple cancer centers in China.<br /><br />In conclusion, while savolitinib demonstrates promising efficacy and manageable safety in previously treated METex14 NSCLC patients, those without prior immunotherapy showed a tendency for better outcomes and safety profiles in this analysis.

Asset Subtitle

Yongfeng Yu

Meta Tag

Speaker Yongfeng Yu

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

savolitinib

MET exon 14 skipping mutation

non-small cell lung cancer

NSCLC

prior immunotherapy

immunotherapy-naïve

overall response rate

progression-free survival

treatment-related adverse events

MET tyrosine kinase inhibitors