The SANOVO Phase III trial has moved savolitinib (Orpathys) plus osimertinib into the first-line EGFR-mutated lung cancer setting, showing a statistically significant PFS benefit over AstraZeneca's Tagrisso (osimertinib) alone in treatment-naïve patients with MET-overexpressing tumors in China.
HUTCHMED (China) Limited (Nasdaq: HCM) and AstraZeneca reported that the blinded, randomized, placebo-controlled trial met its primary endpoint in both the high MET subgroup and the intention-to-treat (ITT) population. The combination also produced what the companies described as encouraging early overall survival (OS) data, a secondary endpoint for which follow-up continues. No numerical data — median PFS, hazard ratios, or p-values — were disclosed in the top-line announcement; full results are due at a forthcoming medical meeting.
SANOVO enrolled 326 treatment-naïve patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletion or L858R mutations and MET overexpression, randomized 1:1 to osimertinib 80 mg once daily plus either savolitinib or placebo at weight-based doses of 300 or 200 mg twice daily. Savolitinib is an oral, selective MET tyrosine kinase inhibitor (TKI) that blocks aberrant MET receptor signaling driven by gene amplification, overexpression, or mutation. The safety profile was consistent with the established profiles of each agent, with no new safety findings reported.
The SACHI trial — which compared savolitinib plus osimertinib against platinum-based chemotherapy in patients with MET-amplified EGFR-mutated NSCLC following EGFR-TKI progression — supported approval of the combination in China in June 2025, with median investigator-assessed PFS of 8.2 months versus 4.5 months for chemotherapy. Two weeks before SANOVO, the global SAFFRON Phase III trial reported statistically significant improvements in both PFS and OS versus chemotherapy in the post-osimertinib setting, providing the evidence base for potential US and global regulatory filings.
SANOVO is distinct from both predecessors in moving dual EGFR/MET blockade into the first-line setting, testing whether adding savolitinib upfront can delay progression in tumors already displaying MET overexpression before treatment, rather than targeting MET-driven resistance after EGFR-TKI progression.