TAGRISSO (osimertinib) plus savolitinib reduced the risk of disease progression or death by 45% and the risk of death by 32% in MET-driven EGFR-mutated lung cancer after[...]

TAGRISSO plus savolitinib extended median overall survival by nearly five months

SAFFRON is first global Phase III trial to show significant
progression-free and overall survival benefit in this setting,
reinforcing TAGRISSO as backbone therapy across EGFRm lung cancer

Positive results from the SAFFRON Phase III trial showed TAGRISSO^® (osimertinib) plus savolitinib 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.

These results will be presented today during the Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain (abstract #LBA6).¹ They were also simultaneously published in The New England Journal of Medicine.

Results showed TAGRISSO plus savolitinib reduced the risk of disease progression or death by 45% compared to chemotherapy (based on a PFS hazard ratio [HR] of 0.55; 95% confidence interval [CI] 0.42-0.72; p<0.001). Median PFS as assessed by blinded independent central review (BICR) was 7.6 months for TAGRISSO plus savolitinib versus 5.4 months for the comparator arm. An estimated 36% of patients treated with the combination were progression-free at one year compared to 10% in the comparator arm. Importantly, the PFS benefit observed was consistent across all prespecified subgroups, including patients whose tumors had MET-overexpression or MET-amplification.

Results for the key secondary endpoint of OS showed TAGRISSO plus savolitinib reduced the risk of death by 32% versus chemotherapy (OS HR 0.68; 95% CI 0.50-0.91; p=0.010). TAGRISSO plus savolitinib extended median OS by 4.9 months versus the comparator arm (17.8 versus 12.9 months). An estimated 70% of patients treated with the combination were alive at one year compared to 53% in the comparator arm.

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 results have the potential to establish a new global standard of care for the third of patients with EGFR-mutated non-small cell lung cancer experiencing high levels of MET-driven resistance after osimertinib. There are currently no well-tolerated, oral, biomarker-directed treatment options to address this frequent driver of disease progression. Osimertinib plus savolitinib significantly extended median overall survival by nearly five months in this later-line setting, establishing a new clinical benchmark and reinforcing the critical need for MET testing to guide patient care."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "These data show combining savolitinib with backbone therapy TAGRISSO directly addresses MET-driven resistance while maintaining EGFR suppression, building on the established efficacy, safety and central nervous system protection of TAGRISSO. With the potential to become the first biomarker-directed, all-oral treatment option in this setting, this combination further strengthens our leadership in EGFR-mutated lung cancer and reflects our strategy of matching the right therapy to the underlying drivers of disease at every stage."

Johnny Cheng, Acting Chief Executive Officer and Chief Financial Officer,, HUTCHMED, said: "These data from SAFFRON mark a decisive step forward in targeting MET-driven resistance-a longstanding challenge in EGFR-mutated lung cancer. Precision inhibition with savolitinib alongside TAGRISSO offers a meaningful, all-oral option for patients with disease progression. We are delighted to see that our partnership with AstraZeneca continues to deliver impactful innovations that have the potential to redefine standard of care and improve outcomes for patients globally."

Summary of PFS and OS results: SAFFRONⁱ

The safety profile for TAGRISSO plus savolitinib was manageable and consistent with the known profiles of each medicine, and there were no new safety concerns. Grade 3 or higher treatment-emergent adverse events from all causes occurred in 64% of patients treated with TAGRISSO plus savolitinib and 63% of patients in the comparator arm. Median total duration of treatment exposure was more than twice as long for TAGRISSO plus savolitinib (8.5 months) compared with the comparator arm (3.5 months).

Based on the SAFFRON Phase III trial results, a New Drug Application (NDA) for TAGRISSO plus savolitinib was submitted to the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic NSCLC whose tumors have MET overexpression or amplification and who had disease progression on or after an EGFR-tyrosine kinase inhibitor (TKI) therapy. TAGRISSO plus savolitinib is approved in China for patients with locally advanced or metastatic EGFRm-positive non-squamous NSCLC with MET amplification after disease progression on EGFR-TKI therapy based on the SACHI Phase III trial.

Results from the SANOVO Phase III trial evaluating TAGRISSO plus savolitinib in treatment-naive patients in China with EGFRm locally advanced or metastatic NSCLC and MET overexpression will be presented tomorrow during a Proffered Paper session at the ESMO Congress (abstract #LBA69).²

Savolitinib is being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca.

IMPORTANT SAFETY INFORMATION

• There are no contraindications for TAGRISSO
• TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal
  • ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy: In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 0.4% of cases were fatal
  • ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT): In the LAURA study, following definitive platinum-based CRT, ILD/pneumonitis including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo. There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO-treated patients, ILD/pneumonitis led to permanent discontinuation of TAGRISSO in 7% of patients and dosage interruptions of TAGRISSO in 35% of patients. Among the 46 patients who were rechallenged with TAGRISSO, 11% had recurrence of ILD/pneumonitis. In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%

For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis

• TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
• TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
• Keratitis was reported in 0.6% of 1813 patients treated with TAGRISSO monotherapy in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
• Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed
• Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
• Aplastic anemia has been reported in TAGRISSO-treated patients in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
• Myalgia occurred in 4.8% of patients in the pooled safety population who received TAGRISSO as a monotherapy (n=1813), of these, 0.1% were grade 3. Myalgia with concurrent increased creatinine phosphokinase (CPK) elevation occurred in 0.1% of patients. The median time to onset of myalgia for these patients with CPK elevation was 648 days (range: 141 days to 1155 days). Grade 1 myositis occurred in 0.2% of patients who received TAGRISSO. Rhabdomyolysis has been reported in the post-marketing setting. Advise patients to report unexplained muscle pain or tenderness. Monitor CPK levels periodically during treatment with TAGRISSO and as clinically indicated in patients reporting unexplained muscle pain or tenderness. Withhold, then resume at the same or reduced dose
• Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose
• Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose
• Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
  • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
  • TAGRISSO monotherapy following platinum-based chemoradiation therapy: lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough and COVID-19
  • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

• TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
• TAGRISSO is indicated for the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
• TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
• TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
• TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescribing Information, including Patient Information for TAGRISSO.

Notes

NSCLC and MET aberrations

Lung cancer is the leading cause of cancer death globally, accounting for almost one in five (19%) cancer deaths.^3,4 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC.⁵ Approximately 75% of NSCLC patients are diagnosed with advanced disease.⁶ Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFRm NSCLC.⁷

MET is a tyrosine kinase receptor that has an essential role in normal cell development.⁸ MET overexpression or amplification can lead to tumor growth and the metastatic progression of cancer cells.^8-9 Approximately one in three patients' tumors will develop high levels of MET overexpression or amplification (IHC3+>90% and FISH10+) after progression on a third-generation EGFR-TKI.¹⁰

SAFFRON
SAFFRON is a randomized, open-label, multi-center, global Phase III trial studying the efficacy of savolitinib (300 mg twice daily) added to TAGRISSO (80 mg once daily) versus doublet platinum-based chemotherapy in 338 patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression or amplification whose disease progressed following 1st- or 2nd-line treatment with TAGRISSO. The trial enrolled patients in 230 centers across 29 countries, including in North America, Europe, South America and Asia. The primary endpoint is PFS and key secondary endpoints include OS and objective response rate.

Patients were prospectively selected for SAFFRON using the high MET level cut-offs identified in the SAVANNAH Phase II trial.​ In SAVANNAH, MET overexpression or amplification levels were determined by two tests: immunohistochemistry (IHC), which detects if cancer cells have a particular protein or marker on their surface, and fluorescence in situ hybridization (FISH), which detects a specific DNA sequence from cancer cells.

Savolitinib

Savolitinib is an oral, potent and highly selective MET-TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Savolitinib is approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. Savolitinib also received a conditional approval in China for the treatment of patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with MET amplification who have failed at least two prior systemic treatments.

Savolitinib in combination with TAGRISSO was granted a temporary authorization in Switzerland for the treatment of patients with locally advanced or metastatic EGFRm NSCLC and high levels of MET overexpression or amplification who progressed on prior treatment with TAGRISSO. This was based on results from the global SAVANNAH Phase II trial.

TAGRISSO^® (osimertinib)

TAGRISSO^® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including the treatment of central nervous system metastases. TAGRISSO (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

TAGRISSO is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy. TAGRISSO is also approved in combination with chemotherapy in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, TAGRISSO demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. TAGRISSO is also being investigated in this setting in combination with datopotamab deruxtecan-dlnk in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

TAGRISSO also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials and in locally advanced stages in the LAURA Phase III trial. As part of AstraZeneca's ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

AstraZeneca in lung cancer

AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company's comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including TAGRISSO and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan-dlnk in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology 

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca.

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References

1. Lu S, et al. Osimertinib [osi] + savolitinib [savo] vs platinum-pemetrexed [plat-pem] in EGFRm MET-overexpressed [OE] and/or -amplified [AMP] advanced NSCLC post-osi: SAFFRON Phase [Ph] 3 primary results. Presented in a Proffered Paper session during Presidential Symposium II at the European Society for Medical Oncology Congress 2026, 25 October at 16:45 CET.

2. Wu YL, et al. Savolitinib or Placebo Combined with Osimertinib in Treatment-Naïve Advanced NSCLC with EGFR Mutation and MET Overexpression: Results from the Phase 3 SANOVO Study. Presented at the European Society for Medical Oncology Congress 2026, 26 October at 08:30 CET.

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 October 2026.

4. World Health Organization. International Agency for Research on Cancer. All Cancers Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/39-all-cancers-fact-sheet.pdf. Accessed October 2026.

5. American Cancer Society. What Is Lung Cancer? Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed October 2026.

6. Chen HJ, et al. Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI. Medicine. 2021;100(6):e24688.

7. Gao X, et al. The safety and efficacy of osimertinib for the treatment of EGFR T790M mutation positive non-small-cell lung cancer. Expert Rev Anticancer Ther. 2016;16(4):383-390.

8. Uchikawa E, et al. Structural basis of the activation of c-MET receptor. Nat Commun. 2021;12(4074).

9. Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer. J Hematol Oncol. 2019;63.

10. 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.