AstraZeneca submitted a New Drug Application to the US FDA for savolitinib (Orpathys) plus osimertinib (Tagrisso) in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) whose tumors have MET overexpression or amplification and whose disease progressed on or after an EGFR tyrosine kinase inhibitor. Savolitinib was discovered by China-based HutchMed (Nasdaq/AIM: HCM; HKEX: 13), which has partnered with AstraZeneca on the MET inhibitor since 2011, with AstraZeneca leading development outside China.
Under the companies' global licensing and co-development agreement, HutchMed leads savolitinib development in China, while AstraZeneca leads and funds development elsewhere and is responsible for commercialization globally. HutchMed manufactures and supplies the drug in China, where it is already marketed as Orpathys.
The filing is supported by the global Phase III SAFFRON trial, which compared savolitinib plus osimertinib with platinum-based chemotherapy in 338 patients whose disease progressed after first- or second-line osimertinib. AstraZeneca and HutchMed reported statistically significant and clinically meaningful improvements in both progression-free survival and overall survival, although numerical efficacy results have not yet been disclosed.
MET activation is a common mechanism of resistance to EGFR TKIs, and the companies estimate that high MET overexpression or amplification develops in around 34% of tumors after progression on a third-generation EGFR TKI. Savolitinib is a selective MET inhibitor jointly developed by AstraZeneca and HutchMed.
In the US, Johnson & Johnson's Rybrevant (amivantamab) plus carboplatin and pemetrexed is approved after EGFR-TKI progression in EGFR exon 19 deletion or L858R NSCLC without restriction to MET-positive disease. Approved selective MET inhibitors such as capmatinib (Tabrecta; Novartis) and tepotinib (Tepmetko; Merck KGaA) are indicated for MET exon 14 skipping rather than acquired MET overexpression or amplification.