Tagrisso combined with Orpathys shows statistically significant and clinically meaningful gains in progression free and overall survival for MET driven EGFR mutated lung cancer after progression on Tagrisso

Top line results from the Phase III SAFFRON trial showed that adding Orpathys (savolitinib) to Tagrisso (osimertinib) achieved a statistically significant and clinically meaningful improvement in both progression free survival and overall survival, compared with standard doublet platinum based chemotherapy, in patients with epidermal growth factor receptor mutated non small cell lung cancer whose disease had progressed on prior Tagrisso treatment. These patients’ tumors showed high levels of MET overexpression or amplification, a common driver of resistance to EGFR inhibitors, and were then treated with the Tagrisso and Orpathys combination rather than Tagrisso alone.

Top line results from the Phase III SAFFRON trial showed that Tagrisso (osimertinib) combined with Orpathys (savolitinib) achieved a statistically significant and clinically meaningful improvement in both progression free survival and overall survival compared with standard doublet platinum based chemotherapy in patients with epidermal growth factor receptor mutated non small cell lung cancer. Participants in the trial had tumors showing high levels of MET overexpression or amplification and had already progressed on prior treatment with Tagrisso.

Third generation EGFR tyrosine kinase inhibitors have meaningfully improved outcomes for patients with EGFR mutated non small cell lung cancer. Even so, roughly one in three patients eventually develop MET overexpression or amplification in their tumors, making it one of the most frequent mechanisms behind resistance to third generation EGFR inhibitors. Resistance driven by MET tends to carry a poor prognosis, and there remains a substantial unmet need for treatment options in later treatment lines that are both effective and well tolerated.

Professor Shun Lu, director of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, part of Shanghai Jiao Tong University School of Medicine, and principal investigator of the trial, called the SAFFRON results an important advance for patients with EGFR mutated non small cell lung cancer who develop MET driven resistance after osimertinib, a group that has historically faced poor outcomes and lacked oral, well tolerated, biomarker guided treatment options. He noted that MET is among the most common drivers of disease progression on targeted therapy in this setting, and said the data highlight both the potential of this new osimertinib and savolitinib combination and the importance of testing for MET status to guide treatment decisions.

Susan Galbraith, executive vice president of oncology haematology research and development at AstraZeneca, said the results show a clear benefit from adding Orpathys to Tagrisso, the backbone therapy, in order to address MET overexpression or amplification while continuing to suppress EGFR activity. She said the combination, building on Tagrisso’s established efficacy, safety profile, and ability to protect the central nervous system, is intended to offer patients worldwide the first all oral, biomarker guided option in this setting. She added that the results further reinforce the company’s leading position in EGFR mutated lung cancer and its broader strategy of improving outcomes across disease stages and treatment lines through novel combinations.

Weiguo Su, chief executive officer and chief scientific officer of HUTCHMED, said that overcoming MET driven resistance following EGFR inhibitor therapy has long been a persistent challenge in clinical practice. He said the global SAFFRON study builds on the strong efficacy already shown in the Phase III SACHI trial, which supported approval in China, and provides clear evidence to support registration of the Tagrisso and Orpathys combination in other markets globally. He thanked everyone who contributed to the trial and said HUTCHMED looks forward to working with AstraZeneca to potentially bring the treatment to patients worldwide.

The safety profile observed for the Tagrisso and Orpathys combination was consistent with what is already known about each medicine individually, and no new safety issues emerged. These results are expected to be presented at an upcoming medical conference and shared with regulatory authorities around the world.

The combination of Tagrisso and Orpathys is currently approved in China for patients with locally advanced or metastatic EGFR mutated non small cell lung cancer with MET amplification who have progressed after EGFR inhibitor therapy, based on findings from the Phase III SACHI trial.

---

---

Related Topics and Keywords

egfr mutated lung cancer, Orpathys, Tagrisso