Tagrisso plus Orpathys cut the risk of death by 32 percent and the risk of progression or death by 45 percent in MET-driven EGFR-mutated lung cancer after Tagrisso, in Phase III results presented at ESMO and published in The New England Journal of Medicine.
AstraZeneca and HUTCHMED reported positive results from the global Phase III SAFFRON trial, showing that Tagrisso combined with Orpathys cut the risk of disease progression or death by 45 percent compared with chemotherapy in patients whose EGFR-mutated lung cancer had progressed after Tagrisso and whose tumours showed high levels of MET overexpression or amplification. The results were presented at the European Society for Medical Oncology Congress in Madrid and published at the same time in The New England Journal of Medicine.
Median progression-free survival reached 7.6 months with the combination against 5.4 months with doublet platinum-based chemotherapy, a hazard ratio of 0.55, while median overall survival reached 17.8 months against 12.9 months, a hazard ratio of 0.68, or a 32 percent lower risk of death. At twelve months, an estimated 36 percent of patients on the combination remained progression-free against 10 percent on chemotherapy, and 70 percent were alive against 53 percent. The trial enrolled 338 patients, 171 on the combination and 167 on chemotherapy.
The population matters because MET-driven resistance is the problem the combination is built to solve: patients had already progressed on Tagrisso, and the trial selected only those whose tumours carried high MET levels. HUTCHMED and AstraZeneca said a new drug application has been submitted to the US Food and Drug Administration, with submissions in Europe and Japan progressing, and the combination is already approved in China for patients with MET amplification who progressed on an EGFR inhibitor.
The headline numbers are the same across AstraZeneca's own release, HUTCHMED's release and the independent trial write-up in OncLive, which also gives the patient counts and the data cutoff of July 6, 2026, so the survival and progression figures rest on more than one account of the same dataset. Two limits still apply: the combination is not yet approved in the United States, since the FDA application is submitted rather than granted, and the claim that this is the first global Phase III trial to show a survival benefit in this setting is the companies' own characterisation, not a regulator's finding.
For patients who run out of options when Tagrisso stops working, a targeted oral combination that adds nearly five months of median survival would change the next step after progression, if regulators agree. AstraZeneca's oncology research head told Fierce Pharma that about a third of patients with EGFR-mutant lung cancer develop MET overexpression or amplification after third-generation EGFR drugs, which sets the size of the group this result could reach. The next step that will confirm or change the story is the FDA's decision on the submitted application, alongside the European and Japanese filings.