Hong Kong, Shanghai & Florham Park, N.J., Aug. 17, 2026
HUTCHMED (China) Limited announced positive high-level results from the global Phase III SAFFRON trial, showing that ORPATHYS® (savolitinib) plus TAGRISSO® (osimertinib) produced statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) compared with doublet platinum-based chemotherapy in patients with EGFR-mutated non-small cell lung cancer (NSCLC) whose disease progressed following TAGRISSO treatment. The trial focused on patients whose tumors demonstrated high levels of MET overexpression or amplification, a recognized mechanism of resistance to third-generation EGFR-targeted therapies. The results represent an important development for patients with MET-driven resistance after osimertinib, a setting where treatment options remain limited. The SAFFRON findings also strengthen the clinical rationale for combining MET inhibition with continued EGFR suppression in previously treated EGFR-mutated lung cancer.
SAFFRON Demonstrates Significant PFS and OS Benefits
The SAFFRON Phase III trial is a randomized, open-label, multicenter global study evaluating ORPATHYS at 300 mg twice daily in combination with TAGRISSO at 80 mg once daily against doublet platinum-based chemotherapy. The study enrolled 338 patients across 230 centers in 29 countries, including sites across North America, Europe, South America and Asia. Patients had locally advanced or metastatic EGFR-mutated NSCLC with MET overexpression or amplification and had experienced disease progression following first- or second-line TAGRISSO therapy. The primary endpoint was PFS, while key secondary endpoints included OS and objective response rate (ORR). HUTCHMED reported that the combination achieved a statistically significant and clinically meaningful improvement in both major survival measures. Importantly, the safety profile of ORPATHYS plus TAGRISSO remained consistent with the known profiles of the individual medicines, with no new safety findings reported. Detailed SAFFRON data are expected to be presented at a future medical meeting and submitted to global regulatory authorities.
MET-Driven Resistance Remains a Major Challenge
The clinical significance of the SAFFRON results is closely linked to the role of MET-driven resistance in EGFR-mutated lung cancer. Although third-generation EGFR tyrosine kinase inhibitors have substantially improved outcomes, a significant proportion of tumors can develop MET overexpression or amplification after treatment, allowing cancer cells to bypass EGFR inhibition and continue growing. HUTCHMED noted that approximately one in three patients may develop this mechanism following third-generation EGFR-TKI treatment. SAFFRON prospectively selected patients using high MET thresholds established in the earlier SAVANNAH Phase II study, using immunohistochemistry and fluorescence in situ hybridization to identify relevant MET alterations. The positive Phase III findings therefore provide clinical support for a biomarker-directed treatment strategy targeting MET while maintaining EGFR suppression with TAGRISSO. The combination is already approved in China for certain EGFR-mutated NSCLC patients with MET amplification after progression on EGFR-TKI therapy based on the SACHI Phase III trial.
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ORPATHYS Plus TAGRISSO Supports Global Development
The SAFFRON results expand the evidence supporting ORPATHYS plus TAGRISSO and could become an important foundation for potential regulatory submissions outside China. ORPATHYS is an oral, selective MET tyrosine kinase inhibitor designed to block aberrant MET signaling associated with amplification, overexpression and certain MET alterations, while TAGRISSO remains an established third-generation EGFR-TKI for EGFR-mutated NSCLC. The combination is being jointly developed by HUTCHMED and AstraZeneca, with AstraZeneca responsible for commercialization. HUTCHMED said the SAFFRON findings reinforce the efficacy previously observed in the SACHI Phase III trial and support plans for global registrations. For the broader lung cancer treatment landscape, the results highlight the importance of identifying MET-driven resistance after EGFR-targeted therapy and provide further evidence for a targeted combination approach in patients who progress on TAGRISSO. The positive PFS and OS findings establish SAFFRON as a significant clinical milestone for HUTCHMED and the development of biomarker-guided treatment options in advanced EGFR-mutated NSCLC.
Source: HUTCHMED press relese
