HUTCHMED (China) Limited (HUTCHMED) today announced positive results from the global Phase III SAFFRON study. In patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer, the combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared with platinum-based doublet chemotherapy. Patients in the study had tumors with high-level MET overexpression or amplification and had experienced disease progression following prior treatment with TAGRISSO®.
These results were presented during the Presidential Symposium session at the 2026 European Society for Medical Oncology (ESMO) Congress held in Madrid, Spain (abstract number #LBA6), and were simultaneously published in The New England Journal of Medicine. The high-profile presentation at the premier academic gathering in oncology and in a flagship medical journal underscores the pivotal role of the SAFFRON study in reshaping the treatment landscape for MET-driven EGFR-mutated non-small cell lung cancer. The data confirm that the combination of ORPATHYS® and TAGRISSO® offers a landmark all-oral treatment regimen to address the significant unmet clinical need of MET-driven resistance following third-generation EGFR tyrosine kinase inhibitor (TKI) therapy.
Study results showed that the combination of ORPATHYS® and TAGRISSO® reduced the risk of disease progression or death by 45% compared with chemotherapy (based on PFS hazard ratio [HR] 0.55; 95% confidence interval [CI] 0.42-0.72; p<0.001). Median PFS assessed by blinded independent central review (BICR) was 7.6 months for the ORPATHYS® and TAGRISSO® combination group versus 5.4 months for the control group. An estimated 36% of patients in the combination group remained free of disease progression at one year, compared with 10% in the control group. Notably, consistent PFS benefit was observed across all prespecified subgroups, including patients with MET overexpression and MET amplification.
Results for the key secondary endpoint of OS showed that the combination of ORPATHYS® and TAGRISSO® reduced the risk of death by 32% compared with chemotherapy (OS HR 0.68; 95% CI 0.50-0.91; p=0.010). The ORPATHYS® and TAGRISSO® combination group extended median OS by 4.9 months (17.8 months versus 12.9 months). An estimated 70% of patients in the combination group were still alive at one year, compared with 53% in the control group.
Professor Lu Shun, the study's global principal investigator and Director of the Shanghai Lung Cancer Center at Shanghai Chest Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, said: "These results are expected to establish a new global treatment standard for approximately one-third of patients with EGFR-mutated non-small cell lung cancer who develop MET-driven resistance after osimertinib treatment. For this common driver of disease progression, there is currently no well-tolerated, biomarker-directed oral treatment option. In this later-line treatment setting, savolitinib combined with osimertinib significantly extended median overall survival by nearly 5 months, with the potential to set a new clinical benchmark and highlighting the urgent need for MET testing to guide patient treatment."
Mr. Zheng Zefeng, Acting Chief Executive Officer and Chief Financial Officer of HUTCHMED, said: "The SAFFRON study data mark a decisive step forward in addressing MET-driven resistance, which has long been a major challenge in EGFR-mutated lung cancer. The combination of ORPATHYS® and TAGRISSO® delivers precise inhibition, offering a highly meaningful all-oral treatment option for patients with disease progression. We are pleased to see our collaboration with AstraZeneca continue to deliver impactful innovations that reshape treatment standards and improve outcomes for patients worldwide."
Dr. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, said: "These data demonstrate that combining ORPATHYS® with the cornerstone therapy TAGRISSO® can directly address MET-driven resistance mechanisms while continuing to inhibit EGFR, building on the established efficacy, safety, and central nervous system protective effects of TAGRISSO®. This combination has the potential to become the first biomarker-directed all-oral treatment option in this therapeutic area, further consolidating our leadership in EGFR-mutated lung cancer and reflecting our strategy of matching the appropriate therapy to the underlying driver across all stages of the disease."
Comments