AstraZeneca's Tagrisso-Orpathys Combination Demonstrates Survival Gains in Resistant Lung Cancer
Phase III SAFFRON trial shows statistically significant improvements in progression-free and overall survival for EGFR-mutated NSCLC patients with MET-driven resistance.
Trial Results
AstraZeneca announced positive high-level results from its SAFFRON Phase III trial, showing that the combination of Tagrisso (osimertinib) and Orpathys (savolitinib) demonstrated statistically significant and clinically meaningful improvements in both progression-free survival and overall survival versus doublet platinum-based chemotherapy (6-K filing, 2026-08-17). The trial enrolled patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours had high levels of MET overexpression or amplification and had progressed on prior Tagrisso treatment.
The SAFFRON trial randomized 338 patients across 230 centres in 29 countries, including North America, Europe, South America and Asia (6-K filing, 2026-08-17). The safety profile was consistent with the known profiles of each medicine, with no new safety findings reported.
Addressing Resistance Mechanisms
MET-driven resistance represents a significant clinical challenge in EGFR-mutated lung cancer. According to the filing, an estimated 34% of tumours develop high levels of MET overexpression or amplification after progression on a third-generation EGFR-tyrosine kinase inhibitor (6-K filing, 2026-08-17). This mechanism of resistance is associated with poor prognosis and represents a population with limited treatment options.
Professor Shun Lu, Director of Shanghai Lung Cancer Center and principal investigator, stated that the results "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" (6-K filing, 2026-08-17).
Regulatory and Commercial Status
The Tagrisso plus Orpathys combination is already 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 earlier SACHI Phase III trial (6-K filing, 2026-08-17). The combination also received temporary authorization in Switzerland for treatment of patients with high levels of MET overexpression or amplification who progressed on prior Tagrisso treatment.
AstraZeneca indicated it will present the SAFFRON data at a forthcoming medical meeting and share results with global regulatory authorities (6-K filing, 2026-08-17). Orpathys is being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca.
Market Context
Lung cancer accounts for nearly one in four (23%) cancer deaths globally, making it the leading cause of cancer mortality (6-K filing, 2026-08-17). Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFRm NSCLC.
Tagrisso has been used to treat more than one million patients across its indications worldwide and is approved as monotherapy in more than 120 countries (6-K filing, 2026-08-17). The drug is also approved in combination with chemotherapy in more than 80 countries for first-line treatment of locally advanced or metastatic EGFRm NSCLC.
According to MarginX data, AstraZeneca is scheduled to present at the SEB Nordic Large Cap Seminar on August 18, 2026, and the Handelsbanken Life Science Innovation Day on August 25, 2026.
This article was generated by MarginX from the 6-K filing on 2026-08-17. It is not investment advice.