HUTCHMED SANOVO trial shows PFS gain for savolitinib plus osimertinib
HUTCHMED has reported positive high-level results from its SANOVO Phase III trial, showing that savolitinib (ORPATHYS) combined with osimertinib (TAGRISSO) delivered a statistically significant improvement in progression-free survival over osimertinib alone in treatment-naïve patients with locally advanced or metastatic NSCLC harbouring EGFR mutations and MET overexpression.
The benefit was observed in both the high MET overexpression subgroup and the intention-to-treat population. The combination also showed what HUTCHMED described as an encouraging early signal in overall survival, a secondary endpoint, though the trial will continue to collect follow-up data. Full results have not yet been released and are expected to be presented at a forthcoming medical conference. No hazard ratios, response rates, or median PFS figures were included in the announcement.
Trial design and patient population
SANOVO was a blinded, randomised, placebo-controlled study conducted in China, enrolling 326 previously untreated patients with locally advanced or metastatic NSCLC carrying EGFR exon 19 deletion or L858R mutations alongside MET overexpression. Patients were randomised 1:1 to receive osimertinib 80 mg once daily together with either savolitinib or placebo, dosed at 300 mg or 200 mg twice daily depending on body weight. The safety profile was consistent with the known profiles of each agent individually, with no new findings reported.
Professor Yi-Long Wu of the Guangdong Provincial People's Hospital, the trial's leading principal investigator, said the results demonstrate "that addressing both pathways upfront with an all-oral, biomarker-directed regimen offers a powerful new approach for these patients whose tumours have MET overexpression."
Savolitinib is jointly developed by HUTCHMED and AstraZeneca and is already approved in China in combination with osimertinib for EGFR-mutated NSCLC patients with MET amplification who have progressed on prior EGFR TKI therapy, based on the earlier SACHI Phase III trial. A separate global Phase III programme, SAFFRON, reported positive high-level PFS and OS results in the same pre-treated setting just days before the SANOVO readout, making this a significant accumulation of evidence for the partnership in a short window.
Market context and competitive landscape
The EGFR-mutated NSCLC space is one of the most competitive in oncology. Osimertinib already dominates the first-line setting globally, but co-occurring MET aberrations are increasingly recognised as a driver of primary and acquired resistance to EGFR-targeted therapy. Estimates suggest MET overexpression or amplification is present in a meaningful proportion of EGFRm NSCLC patients at diagnosis, though precise rates vary by testing methodology and population.
Several companies are investigating MET-directed strategies to shore up front-line EGFR TKI efficacy. Amivantamab, an EGFR-MET bispecific antibody from Johnson and Johnson, is approved in some settings and is being studied in combination with chemotherapy and other backbones. The HUTCHMED and AstraZeneca approach is notable for being all-oral, which carries practical advantages for patients and healthcare systems when set against intravenous bispecific regimens.
HUTCHMED has said it intends to share the SANOVO data with regulatory authorities in China, signalling an intent to seek a label extension for the savolitinib-osimertinib combination into the front-line setting. Given that the combination already holds approval in the second-line setting in China, the regulatory precedent is supportive, though a full data package including mature OS and safety data will be expected before any label decision.
Investors will be watching closely for the full dataset presentation, which will include the hazard ratio for PFS, subgroup analyses by MET overexpression level, and longer-term OS trends. The distinction between MET overexpression and MET amplification as patient selection criteria will also attract scrutiny, as the two biomarkers do not always co-occur and clinical benefit may diverge across subgroups.