Adding Hutchmed’s Orpathys (savolitinib) to AstraZeneca’s Tagrisso (osimertinib) cut the risk of disease progression or death by 45 percent and the risk of death by 32 percent against doublet platinum chemotherapy in patients with EGFR-mutated non-small cell lung cancer whose tumours had high MET overexpression or amplification and who had already progressed on Tagrisso, in the global Phase 3 SAFFRON trial presented at ESMO on October 25 and published simultaneously in The New England Journal of Medicine. Median progression-free survival was 7.6 months on the combination against 5.4 months on chemotherapy (hazard ratio 0.55, 95 percent confidence interval 0.42 to 0.72, p below 0.001), and median overall survival was 17.8 months against 12.9 months (hazard ratio 0.68, 95 percent confidence interval 0.50 to 0.91, p=0.010), a gain of nearly five months. An estimated 36 percent of combination patients were progression-free at one year against 10 percent on chemotherapy, and 70 percent were alive at one year against 53 percent.
The population is biomarker-selected and large. About a third of patients with EGFR-mutated lung cancer develop MET overexpression or amplification after a third-generation EGFR inhibitor, AstraZeneca’s oncology research head Susan Galbraith told Fierce Pharma, and the progression benefit was consistent across the prespecified subgroups, including MET-overexpression and MET-amplification groups, the companies said. The regimen is all-oral, which is part of its competitive claim against chemotherapy in this setting.
The regulatory path is already moving. Fierce Pharma reported that AstraZeneca filed for FDA approval in September on the SAFFRON results, and Hutchmed said submissions in Europe and Japan are progressing. Orpathys has been approved in China since 2021 in a related setting, but a United States approval has taken more than five years longer, after AstraZeneca narrowed the program’s focus during Phase 2.
For AstraZeneca, the strategic point is franchise defence. Tagrisso is the backbone of its lung cancer business, and SAFFRON gives patients a reason to stay on it, with a targeted partner drug, after the resistance mechanism that normally ends its use. The trial’s global leading investigator, Shun Lu of Shanghai Chest Hospital, said the results could establish a new global standard of care for this population and reinforce the need for MET testing at progression.