SANOVO Signals a First-Line Shift in EGFR-Mutated NSCLC: Savolitinib Plus Osimertinib Delivers a 24.9-Month Median PFS
Savolitinib (ORPATHYS) plus osimertinib (TAGRISSO) is an investigational first-line combination designed to address concurrent EGFR-driven tumor growth and MET-associated signaling in advanced non-small cell lung cancer (NSCLC). Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI), while savolitinib is an oral, selective MET inhibitor that targets MET pathway activation associated with protein overexpression, gene amplification, and certain mutations. The combination aims to improve disease control in patients whose co-occurring MET overexpression may limit the effectiveness of EGFR-TKI monotherapy.
The Phase III SANOVO study (NCT05015608) evaluated savolitinib plus osimertinib against placebo plus osimertinib in 326 previously untreated patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletion or L858R mutations and MET overexpression. Conducted in China, the randomized trial assessed progression-free survival (PFS) as its primary endpoint, with overall survival (OS), objective response rate, duration of response, and safety as additional endpoints. Presented at ESMO Congress 2026, the results demonstrated a statistically significant PFS benefit alongside encouraging OS findings for the combination.
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Key Efficacy and Safety Highlights | |||
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Category |
Parameter |
Savolitinib + Osimertinib |
Placebo + Osimertinib |
|
Efficacy |
Patients in efficacy analysis |
162 |
164 |
|
Median PFS, ITT population |
24.9 months |
13.8 months | |
|
PFS hazard ratio |
0.56 |
Comparator arm | |
|
PFS statistical significance |
p < 0.0001 |
Comparator arm | |
|
Median PFS, high MET expression (IHC 3+) |
24.8 months |
11.1 months | |
|
PFS hazard ratio, high MET expression |
0.45 |
Comparator arm | |
|
Median OS, ITT population |
44.5 months |
34.9 months | |
|
OS hazard ratio |
0.48 |
Comparator arm | |
|
Estimated 3-year OS rate |
67.4% |
47.4% | |
|
Safety |
Treatment discontinuation due to adverse events |
14.8% |
Comparator arm |
|
Fatal adverse events, excluding disease progression |
4.3% |
4.8% | |
|
Overall safety assessment |
Manageable; no new safety concerns reported |
Consistent with known safety profile | |
Conclusion
The Phase III SANOVO results position savolitinib plus osimertinib as a promising first-line strategy for treatment-naïve advanced EGFR-mutated NSCLC with MET overexpression. The combination significantly improved PFS compared with osimertinib alone, extending median PFS by 11.1 months in the overall study population and by 13.7 months in patients with high MET expression. Encouraging OS findings further strengthen the clinical rationale for targeting both pathways from the outset. However, the trial was conducted in China, and the first-line combination remains subject to regulatory review. The findings could broaden the role of MET-directed therapy from managing acquired resistance to selecting treatment at diagnosis, reinforcing a shift toward biomarker-driven treatment intensification in molecularly defined NSCLC.