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Savolitinib Plus Osimertinib in Epidermal Growth Factor Receptor-Mutated, MET-Amplified Advanced Non-Small Cell Lung

James Chih-Hsin Yang1, Yuh-Min Chen2, Ullas Batra3

  • 1Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei, Taiwan.

Clinical Lung Cancer
|November 27, 2025
PubMed
Abstract

Insights

Savolitinib combined with osimertinib shows improved outcomes for advanced non-small cell lung cancer (NSCLC) with MET amplification. This combination therapy offers higher response rates and longer progression-free survival in NSCLC patients resistant to initial treatments.

Area of Science:

  • Oncology
  • Medical Research
  • Pharmacology

Background:

  • MET amplification is a primary resistance mechanism to first-line osimertinib treatment in non-small cell lung cancer (NSCLC).
  • Understanding resistance mechanisms is crucial for developing effective therapies for advanced NSCLC.
  • Targeted therapies are essential for managing specific genetic alterations in cancer.

Purpose of the Study:

  • To evaluate the safety and efficacy of savolitinib plus osimertinib in patients with EGFR-mutated, MET-amplified advanced NSCLC.
  • To assess the impact of combining a MET inhibitor (savolitinib) with an EGFR inhibitor (osimertinib) in a resistant NSCLC population.
  • To explore the efficacy of this combination in patients with higher MET amplification cutoffs.

Main Methods:

  • A phase II study enrolled patients with EGFR-mutated, MET-amplified advanced NSCLC who progressed on osimertinib.
  • Patients received either savolitinib plus osimertinib or savolitinib plus placebo.
  • Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety.

Main Results:

  • The savolitinib-osimertinib combination showed a 57% ORR versus 13% for savolitinib-placebo across all patients.
  • Median PFS was 7.4 months with savolitinib-osimertinib compared to 1.6 months with savolitinib-placebo.
  • In patients with higher MET cutoffs, ORR was 63% for the combination arm and median PFS was 8.2 months.

Conclusions:

  • Savolitinib plus osimertinib demonstrated superior clinical activity compared to savolitinib plus placebo.
  • The combination therapy showed promising results in patients with MET-amplified NSCLC, including those with higher MET expression.
  • Further investigation in the SAVANNAH trial (NCT03778229) is ongoing for higher MET biomarker cutoffs.
Keywords:
Contribution of componentsEGFR-TKIMET amplificationMET-TKI

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