AstraZeneca’s Tagrisso-Orpathys combination has significantly extended survival and reduced the risk of death in patients with advanced EGFR-mutated lung cancer whose disease progressed after treatment with Tagrisso, according to results from a global Phase III trial.

 

The combination of Tagrisso (osimertinib) and Orpathys (savolitinib) reduced the risk of death by 32% and the risk of disease progression or death by 45% compared with platinum-based chemotherapy, the SAFFRON trial found.

 

The results, presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid on October 25, showed that patients receiving the drug combination lived a median of 17.8 months, compared with 12.9 months among those receiving chemotherapy — an extension of 4.9 months. The findings were also published simultaneously in The New England Journal of Medicine.

 

The trial marks the first global Phase III study to demonstrate significant improvements in both progression-free survival and overall survival in this patient population, potentially opening the door to a new treatment option for patients whose cancers develop resistance to existing targeted therapy.

 

The SAFFRON trial evaluated the combination in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR mutations and high levels of MET overexpression or amplification — biological changes associated with resistance to treatment.

 

All patients had experienced disease progression following previous treatment with Tagrisso.

 

Median progression-free survival, measured through blinded independent central review, reached 7.6 months with Tagrisso plus Orpathys, compared with 5.4 months with chemotherapy.

 

At 12 months, an estimated 36% of patients receiving the combination remained free of disease progression, against just 10% in the chemotherapy group.

 

The survival advantage also extended to overall survival. An estimated 70% of patients treated with Tagrisso plus Orpathys were alive at one year, compared with 53% of those receiving chemotherapy.

 

The progression-free survival benefit was consistent across all prespecified subgroups, including patients whose tumours had MET overexpression and those with MET amplification.

 

Professor Shun Lu, Director of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine and principal investigator of the trial, said: “These results have the potential to establish a new global standard of care for the third of patients with EGFR-mutated non-small cell lung cancer experiencing high levels of MET-driven resistance after osimertinib. 

 

"There are currently no well-tolerated, oral, biomarker-directed treatment options to address this frequent driver of disease progression. Osimertinib plus savolitinib significantly extended median overall survival by nearly five months in this later-line setting, establishing a new clinical benchmark and reinforcing the critical need for MET testing to guide patient care.”

 

The findings strengthen the case for identifying MET-driven resistance through biomarker testing, allowing treatment to be tailored to the biological mechanisms driving disease progression.

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “These data show combining Orpathys with backbone therapy Tagrisso directly addresses MET-driven resistance while maintaining EGFR suppression, building on the established efficacy, safety and central nervous system protection of Tagrisso. 

 

"With the potential to become the first biomarker-directed, all-oral treatment option in this setting, this combination further strengthens our leadership in EGFR-mutated lung cancer and reflects our strategy of matching the right therapy to the underlying drivers of disease at every stage.”

 

Johnny Cheng, Acting Chief Executive Officer and Chief Financial Officer, HUTCHMED, said: “These data from SAFFRON mark a decisive step forward in targeting MET-driven resistance—a longstanding challenge in EGFR-mutated lung cancer. Precision inhibition with Orpathys alongside Tagrisso offers a meaningful, all-oral option for patients with disease progression. We are delighted to see that our partnership with AstraZeneca continues to deliver impactful innovations that have the potential to redefine standard of care and improve outcomes for patients globally.”