Tagrisso® combined with Orpathys® showed statistically and clinically significant improvements in progression-free survival and overall survival in patients with lung cancer who had disease progression after Tagrisso® treatment and had MET-driven drug-resistant EGFR mutations.
In this type of disease, it is the first* global phase III clinical study to show significant benefit in both progression-free survival and overall survival.
Results from the SAFFRON Phase 3 study further solidify Tagrisso’s status as the cornerstone of the full-course treatment of EGFR-mutant lung cancer
Shanghai, August 17, 2026 — Positive results from the Phase III SAFFRON trial showed that Tagrisso® (osimertinib mesylate, referred to below as “osimertinib”) plus Orpathys® (savolitinib tablets, referred to below as “savolitinib”) produced statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS), compared with platinum-based doublet chemotherapy, in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Patients in the study had tumors with high levels of MET overexpression or amplification and had experienced disease progression after previous osimertinib treatment.
Third-generation EGFR tyrosine kinase inhibitors (TKIs) have significantly improved treatment outcomes for patients with EGFR-mutant NSCLC. 1 However, one-third of patients will develop MET overexpression or amplification, which is one of the most common mechanisms leading to resistance after third-generation EGFR TKI treatment1-2. MET-driven resistance is associated with poor prognosis, and there is currently a huge unmet clinical need for effective and well-tolerated treatment options in the late-line treatment area.
Professor Lu Shun, the principal investigator of the study and director of the Shanghai Lung Cancer Clinical Center of the Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, said: "The exciting results of the SAFFRON study represent a key advance for patients with EGFR-mutated NSCLC who develop MET-driven resistance after osimertinib treatment. Such patients often have poor prognosis, and "In the face of a lack of biomarker-driven and well-tolerated oral treatment options, MET is one of the most common drivers of disease progression after targeted therapy. These data not only demonstrate the potential impact of the innovative combination of osimertinib and savolitinib, but also highlight the urgency of early detection of MET to guide treatment decisions."
Susan, AstraZeneca's Global Executive Vice President and Head of Oncology R&D Galbraith said: "These data show that combining osimertinib with savolitinib on the basis of the cornerstone therapy can continuously inhibit EGFR while addressing MET overexpression or amplification, thus bringing clear benefits to patients. By combining drugs with proven efficacy, safety and central nervous system protection, With the combination of osimertinib and savolitinib, we look forward to bringing the first biomarker-driven all-oral treatment option for this indication to patients around the world. This will further consolidate our leading position in the field of EGFR-mutated lung cancer and strengthen our strategy to improve patient outcomes across stages and lines of treatment."
Dr. Wei Guo Su, CEO and Chief Scientific Officer of HUTCHMED, said: "Overcoming MET-driven resistance after EGFR TKI treatment has long been a challenge in clinical practice. Following SACHI After the Phase III study supports the approval of this therapy in China, the results of the SAFFRON global study further confirm its solid efficacy and will provide clear data support for the global registration of osimertinib and savolitinib combination therapy. We are grateful to everyone involved in this study. We look forward to continuing to work side by side with AstraZeneca to bring this landmark treatment to patients around the world."
The safety profile of the combination therapy of osimertinib and savolitinib is consistent with the known safety profiles of the combination therapy and each monotherapy, and no new safety signals were found. Relevant data will be presented at upcoming academic conferences and shared with global regulatory agencies.
Based on the results of the SACHI phase III clinical trial, the combination therapy of osimertinib and savolitinib has been approved in China for the treatment of patients with locally advanced or metastatic NSCLC with MET-amplified EGFR mutations whose disease has progressed after receiving EGFR-TKI treatment.
Savolitinib was jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca.
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About non-small cell lung cancer and MET abnormalities
Globally, lung cancer is the leading cause of cancer death, accounting for approximately one quarter (23%) of all cancer deaths3. Lung cancer is usually divided into NSCLC and small cell lung cancer, with NSCLC accounting for approximately 80%-85% of all lung cancer patients4. , most (approximately 75%) NSCLC patients are in advanced stages when diagnosed5. Approximately 10-25% of NSCLC patients in the United States and Europe have EGFR mutations, while the proportion is as high as 30-40% in Asian patients6-8.
MET is a receptor tyrosine kinase that plays an important role in the normal development of cells9. MET amplification and/or overexpression can lead to tumor growth and metastatic progression of cancer cells9-10. It is estimated that 34% of patients will develop high-level MET overexpression or amplification after treatment with third-generation EGFR TKIs.
About SAFFRON Clinical Research
SAFFRON is a randomized, open-label, randomized, multicenter, global Phase III study designed to evaluate the efficacy of savolitinib (300 mg twice daily) combined with osimertinib (80 mg once daily) versus platinum-based doublet chemotherapy. The study included a total of 338 patients with EGFR-mutated, locally advanced or metastatic NSCLC, accompanied by MET overexpression or amplification, and who had disease progression after receiving first-line or second-line treatment with osimertinib. The study was conducted at 230 centers in 29 countries around the world, covering North America, Europe, South America and Asia. The primary endpoint of the study is PFS, and key secondary endpoints include OS and objective response rate (ORR).
Patients in the SAFFRON study were prospectively screened based on the high MET expression level threshold established in the SAVANNAH phase II study (n=338). In the SAVANNAH study, the level of MET overexpression or amplification was determined using two tests: immunohistochemical staining (IHC), which detects the presence of specific proteins or markers on the surface of cancer cells; and fluorescence in situ hybridization (FISH), which detects specific DNA sequences in cancer cells.
About savolitinib
Savolitinib is a potent, highly selective, oral TKI for MET, a receptor tyrosine kinase that has shown clinical activity in advanced solid tumors. Savolitinib blocks abnormal activation of the MET receptor tyrosine kinase signaling pathway caused by gene mutations (such as exon 14 skipping or other point mutations), gene amplification, or protein overexpression.
Savolitinib has been approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping mutations, becoming the first selective MET inhibitor approved in China. Savolitinib is also conditionally approved in China for the treatment of adult patients with MET gene-amplified locally advanced or metastatic gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma who have failed at least 2 systemic therapies.
Based on the results of the SACHI Phase III clinical study, savolitinib combined with osimertinib has been approved in China for the treatment of patients with locally advanced or metastatic non-squamous EGFR-mutant NSCLC who have progressed after EGFR TKI treatment and have MET amplification. Based on the results of the SAVANNAH global phase II clinical study, this combination therapy has also received provisional authorization in Switzerland for the treatment of patients with locally advanced or metastatic NSCLC with high-level MET overexpression or amplification of EGFR mutations whose disease has progressed after osimertinib treatment.
About osimertinib
Osimertinib is an irreversible third-generation EGFR-TKI with proven clinical activity in the treatment of patients with EGFR-mutated non-small cell lung cancer (including central nervous system metastases). Osimertinib (40 mg and 80 mg once-daily oral tablets) has treated more than 1 million patients globally across various approved indications. AstraZeneca is continuing to explore osimertinib for the treatment of patients with EGFR-mutated NSCLC across different disease stages.
Osimertinib has been approved as monotherapy in more than 120 countries, including the United States, the European Union, China and Japan. Approved indications include: first-line treatment of NSCLC patients with locally advanced or metastatic EGFR exon 19 deletions or exon 21 (L858R) substitution mutations; patients with disease progression during or after previous treatment with EGFR tyrosine kinase inhibitors (TKIs), and the presence of EGFR has been confirmed by testing Treatment of patients with T790M mutation-positive locally advanced or metastatic NSCLC; treatment of stage IB-IIIA NSCLC patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation; treatment of patients with no disease progression during or after platinum-based chemoradiotherapy, and patients with EGFR exon 19 deletion or exon Treatment of patients with locally advanced, unresectable (stage III) NSCLC harboring 21(L858R) substitution mutations. Osimertinib combined with chemotherapy has been approved in more than 80 countries, including the United States, the European Union, China and Japan, for first-line treatment of patients with locally advanced or metastatic EGFRm-mutated NSCLC.
There is a large amount of evidence supporting osimertinib as a recommended treatment for EGFR-mutated NSCLC. It is a targeted therapy currently proven to improve the clinical outcomes of patients with NSCLC at all stages.
In advanced patients, osimertinib demonstrated improved clinical outcomes both as monotherapy in the FLAURA Phase III study and in combination with chemotherapy in the FLAURA2 Phase III study. In such patients, the TROPION-Lung14 and TROPION-Lung15 Phase III studies of osimertinib in combination with datopotamab deruxtecan are ongoing.
Osimertinib improved clinical outcomes in patients in the NeoADAURA and ADAURA Phase III studies in early-stage patients and in the LAURA Phase III study in locally advanced patients. As an important part of AstraZeneca's ongoing commitment to treating early-stage lung cancer, the ADAURA2 Phase III clinical study is ongoing to evaluate osimertinib as an adjuvant treatment for early-stage resectable lung cancer.
About AstraZeneca’s research in lung cancer
AstraZeneca is working to bring lung cancer patients closer to a cure through detection and treatment of early-stage disease and continues to push scientific boundaries to improve drug resistance and outcomes for patients with advanced lung cancer. The company aims to bring medicines to patients who can benefit most from them by defining new treatment populations and developing innovative therapies.
The company's comprehensive product portfolio includes leading lung cancer drugs and next-generation innovative therapies, including osimertinib and gefitinib, durvalumab and tremelimumab; trastuzumab deruxtecan and datopotamab deruxtecan, developed in partnership with Daiichi Sankyo; savolitinib, developed in partnership with HUTCHMED, as well as a pipeline of new drugs and combinations spanning various mechanisms of action.
AstraZeneca is a founding member of the global Lung Ambition Alliance, which is committed to accelerating innovation and bringing meaningful improvements in and beyond treatment for lung cancer patients.
About AstraZeneca’s research in oncology
AstraZeneca is leading a revolution in the field of oncology and is committed to providing diversified oncology treatment options to scientifically explore the complexity of the oncology field and discover, develop and deliver life-changing medicines to patients.
AstraZeneca's oncology business focuses on the most challenging oncology diseases. Through continuous innovation, AstraZeneca has established a diversified product portfolio and pipeline that leads the industry, continues to promote changes in medical practice and changes patient experience.
AstraZeneca’s vision is to redefine cancer treatment so that it is no longer a leading cause of death.
About AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a science-first global biopharmaceutical company focused on the research, development, production and marketing of prescription drugs, with a focus on oncology, rare diseases and biopharmaceuticals including cardiovascular kidney and metabolism, respiratory and immunity. AstraZeneca's global headquarters is located in Cambridge, UK, with operations in more than 125 countries, and its innovative medicines benefit millions of patients around the world. For more information, please visit www.astrazeneca.com.
About AstraZeneca China
China is AstraZeneca's second largest market in the world and a strategic hub for its global innovation. The company has two global strategic R&D centers in China and has led more than 20 global clinical trials so far. It has four production and supply bases and provides high-quality innovative drugs to more than 70 markets around the world. It has set up a China headquarters in Shanghai and regional headquarters in five places to carry out commercial operations. Since 2023, the company has reached 20 cooperation projects with 17 Chinese innovative pharmaceutical companies. Since entering China in 1993, AstraZeneca has brought nearly 50 innovative drugs to Chinese patients, covering oncology, cardiovascular, renal and metabolic, respiratory and immune, infectious diseases, digestion, rare diseases and other fields. In 2025 alone, the company's innovative drugs will benefit 68 million Chinese patients.
Disclaimer: This article involves products or indications that have not been approved in mainland China. AstraZeneca does not recommend the use of any unapproved drugs.
Source: Internal press release (Approval number: CN-192015)
* The first one, the query deadline is August 27, 2026, applying keywords: "EGFR-mutant NSCLC progressed after EGFR-TKI" and "MET amplification/MET overexpression" and "phase III". Search databases: PubMed, Embase, OVID platform, Ovid full-text journal database, ClinicalTrials.gov
References:
1. De Marinis F, et al. Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study. Ann Oncol. 2025;36(8):920-933.
2. Bar J, et al. Prevalence, molecular characterization, and prognosis of c-Met protein overexpression in a real-world cohort of patients with non-squamous non-small cell lung cancer. Acta Oncol. 2025;64:1544-1553.
3. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed August 2026.
4. American Cancer Society. What Is Lung Cancer? Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed August 2026.
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10. Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer. J Hematol Oncol. 2019;63.