HUTCHMED files US NDA for savolitinib plus osimertinib in NSCLC
HUTCHMED has announced that AstraZeneca has filed a New Drug Application with the US Food and Drug Administration for savolitinib (ORPATHYS) in combination with osimertinib (TAGRISSO) in patients with locally advanced or metastatic non-small cell lung cancer whose tumours show MET overexpression or amplification after progression on an EGFR tyrosine kinase inhibitor.
The filing rests on data from the SAFFRON Phase III trial, which compared the all-oral doublet against platinum-based chemotherapy in 338 patients enrolled across 230 centres in 29 countries. SAFFRON met its primary endpoint of progression-free survival and its key secondary endpoint of overall survival, both with statistical significance, the company said. Full results are scheduled to be presented at a Presidential Symposium at the European Society for Medical Oncology Congress 2026. The safety profile was described as consistent with the known profiles of both agents individually, with no new concerns identified.
Clinical context
MET overexpression or amplification is estimated to emerge in roughly a third of tumours following progression on third-generation EGFR TKI therapy, making it one of the most frequent acquired-resistance mechanisms in this patient population. Current standard of care after EGFR TKI failure has typically reverted to platinum-based chemotherapy, a regimen associated with meaningful toxicity and modest incremental benefit. An all-oral, biomarker-selected combination that improves both PFS and OS in this setting would represent a meaningful shift in practice if approved.
The SAFFRON programme builds on earlier evidence from the SACHI Phase III trial, which supported approval of the savolitinib plus osimertinib combination in China, and the SAVANNAH Phase II trial, which informed the prospective biomarker selection criteria used in SAFFRON. Patients were selected using MET IHC and FISH cut-offs established in SAVANNAH, an approach that reflects the broader industry trend toward tighter biomarker stratification in late-stage oncology trials.
Competitive landscape and regulatory read-across
The MET-driven resistance space in EGFRm NSCLC has attracted attention from several other developers, with tepotinib and capmatinib already approved in MET exon 14-skipping NSCLC and being explored in resistance settings. The savolitinib plus osimertinib combination faces the question of how the FDA will weigh its MET overexpression and amplification-based patient selection against IHC and FISH diagnostic requirements, which add operational complexity to biomarker-directed prescribing. The MHRA and Swiss authorities have already granted the combination regulatory recognition in Europe based on SAVANNAH data, providing some precedent for the FDA review, though the US agency will assess the larger, randomised SAFFRON dataset on its own terms.
Acting chief executive and chief financial officer Johnny Cheng said the filing was "an important step toward potentially bringing ORPATHYS plus TAGRISSO to patients in the US," noting the combination's existing approval in China and the long-standing collaboration between HUTCHMED and AstraZeneca. HUTCHMED co-develops savolitinib, while AstraZeneca leads commercialisation globally.
No PDUFA target date has been disclosed. Investors will watch the ESMO 2026 data presentation for the full survival curves and subgroup analyses that will shape the market's assessment of the combination's commercial opportunity in a US setting where EGFRm NSCLC accounts for roughly 10 to 15 per cent of new NSCLC diagnoses.