Savolitinib (MET TKI) + osimertinib boosts ORR to 49% when MET is truly “high” (IHC3+/≥90% and/or FISH10+)

Savolitinib is an oral, selective MET tyrosine kinase inhibitor being combined with osimertinib (3rd-gen EGFR TKI) to overcome MET-driven resistance after first-line osimertinib in EGFR-mutated advanced NSCLC in the Phase II SAVANNAH study (NCT03778229). In this biomarker cutpoint analysis, response enriched with higher MET—confirmed ORR was 49% in MET IHC3+/≥90% and/or FISH10+ vs 9% without those cutoffs; the looser definition (IHC3+/≥50% and/or FISH5+) delivered a diluted 32% ORR, with estimated prevalence dropping from 62% (looser) to 34% (stricter). As a practical benchmark, post-osimertinib platinum/pemetrexed-based approaches typically sit around ~20%–30% ORR with mPFS ~5–6 months, so the signal here is less “MET-anything helps” and more “MET-high helps” (and needs tight assay thresholds).