HUTCHMED (China) Limited announces that positive high-level results from the SAFFRON Phase III trial showed ORPATHYS^® (savolitinib) plus TAGRISSO^® (osimertinib) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (“PFS”) and overall survival (“OS”) versus doublet platinum-based chemotherapy in patients with epidermal growth factor receptor-mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”). Patients in the trial had tumors with high levels of MET overexpression or amplification and had progressed on prior treatment with TAGRISSO^®.

Third-generation EGFR-tyrosine kinase inhibitors (“TKIs”) have significantly improved outcomes for patients with EGFRm NSCLC.¹ However, one in three patients’ tumors will develop MET overexpression or amplification, one of the most common mechanisms of resistance on third-generation EGFR-TKIs.^1,2 MET-driven resistance is associated with poor prognosis, and there is a significant unmet need for effective and well-tolerated treatment options in later-line settings.²

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 exciting results from SAFFRON represent a critical advance for patients with EGFR-mutated non-small cell lung cancer experiencing MET-driven resistance after osimertinib, a population with poor outcomes and no biomarker-directed treatment options available that are oral and well-tolerated. MET is one of the most common drivers of progression on targeted therapy in this setting, and these data underscore the potential impact of this novel osimertinib plus savolitinib combination and the urgency of MET testing to inform treatment decisions.”

Dr Weiguo Su, Chief Executive Officer^* and Chief Scientific Officer of HUTCHMED, said: “Overcoming MET-driven resistance after EGFR TKI therapy has been a long-standing challenge in clinical practice. The SAFFRON global study further reinforces the robust efficacy previously demonstrated in the SACHI Phase III trial that supported approval in China, with the results providing clear evidence to support global registrations of the TAGRISSO^® and ORPATHYS^® combination. We are grateful to everyone who supported this trial. Together with AstraZeneca, we look forward to potentially bringing this landmark treatment to patients around the world.”

Dr Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca, said: “These data demonstrate the clear benefit of adding ORPATHYS^® to backbone therapy TAGRISSO^® to address MET overexpression or amplification while maintaining EGFR suppression. By combining ORPATHYS^® and TAGRISSO^®, with its established efficacy, safety profile and central nervous system protection, we aim to deliver the first biomarker-directed, all-oral option in this setting to patients across the globe. This further strengthens our leadership in EGFR-mutated lung cancer, reinforcing our strategy to improve patient outcomes across stages and through lines of therapy with novel combinations.”

The safety profile for ORPATHYS^® plus TAGRISSO^® was consistent with the known profiles of each medicine, and there were no new safety findings. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

ORPATHYS^® plus TAGRISSO^® is approved in China for patients with locally advanced or metastatic EGFRm NSCLC with MET amplification after disease progression on EGFR-TKI therapy based on the SACHI Phase III trial.

ORPATHYS^® is being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca.