Tagrisso plus Orpathys improves survival in MET-driven EGFR-mutated lung cancer

AstraZeneca has reported positive Phase III results showing that Tagrisso combined with Orpathys significantly improved both progression-free and overall survival in patients with MET-driven EGFR-mutated non-small cell lung cancer whose disease had progressed following previous Tagrisso treatment.

The findings come from the global SAFFRON study and were presented during a Presidential Symposium at the 2026 European Society for Medical Oncology Congress in Madrid.

Results were also published simultaneously in The New England Journal of Medicine.

Tagrisso, also known as osimertinib, was combined with the MET inhibitor Orpathys, or savolitinib, and compared with platinum-based doublet chemotherapy.

Patients enrolled in SAFFRON had EGFR-mutated non-small cell lung cancer with high levels of MET overexpression or MET amplification following progression on previous Tagrisso therapy.

The combination reduced the risk of disease progression or death by 45% compared with chemotherapy.

The progression-free survival hazard ratio was 0.55, with a 95% confidence interval of 0.42 to 0.72 and a p value below 0.001.

Median progression-free survival assessed by blinded independent central review reached 7.6 months with Tagrisso plus Orpathys compared with 5.4 months in the chemotherapy group.

At one year, an estimated 36% of patients receiving the combination remained progression-free compared with 10% of those receiving chemotherapy.

AstraZeneca said the progression-free survival benefit was consistent across all prespecified subgroups, including patients with MET overexpression and those with MET amplification.

The combination also significantly improved the key secondary endpoint of overall survival.

Tagrisso plus Orpathys reduced the risk of death by 32% compared with chemotherapy, producing an overall survival hazard ratio of 0.68.

Median overall survival reached 17.8 months with the combination compared with 12.9 months with chemotherapy, representing an improvement of 4.9 months.

At one year, an estimated 70% of patients receiving Tagrisso plus Orpathys were alive compared with 53% in the comparator group.

Shun Lu, Professor and Director of the Shanghai Lung Cancer Center at Shanghai Chest Hospital and principal investigator of SAFFRON, said MET-driven resistance represents an important treatment challenge for patients whose EGFR-mutated lung cancer progresses after osimertinib.

He said the results support MET testing to help identify patients who may benefit from biomarker-directed treatment.

Susan Galbraith, Executive Vice President of Oncology Haematology Research and Development at AstraZeneca, said combining Orpathys with Tagrisso is intended to target MET-mediated resistance while continuing to suppress EGFR signalling.

She said the all-oral combination could provide a biomarker-directed alternative to chemotherapy in this later-line setting.

Johnny Cheng, Acting Chief Executive Officer and Chief Financial Officer of HUTCHMED, said the SAFFRON results support the role of precision MET inhibition in addressing resistance to EGFR-targeted treatment.

SAFFRON is the first global Phase III study to demonstrate significant progression-free and overall survival benefits for an oral biomarker-directed combination in this setting.

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