On September 28, 2026 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that AstraZeneca has submitted a New Drug Application ("NDA") to the US Food and Drug Administration ("FDA") for ORPATHYS (savolitinib) plus TAGRISSO (osimertinib) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer ("NSCLC") whose tumors have MET overexpression or amplification, and who had disease progression on or after an epidermal growth factor receptor ("EGFR") tyrosine kinase inhibitor ("TKI") therapy.
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The NDA is supported by the global SAFFRON Phase III trial. SAFFRON showed ORPATHYS plus TAGRISSO 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 who progressed on treatment with TAGRISSO. The safety profile was consistent with the known profiles of each medicine, and there were no new safety concerns. These results will be presented in a Presidential Symposium at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2026.
Third-generation EGFR tyrosine kinase inhibitors ("TKIs") have significantly improved outcomes for patients with EGFRm NSCLC. However, MET overexpression or amplification is one of the most common mechanisms of resistance on third-generation EGFR-TKI treatment. MET-driven progression is associated with poor prognosis, and there remains a significant unmet need for effective and well-tolerated treatment options in this setting.
Mr Johnny Cheng, Acting Chief Executive Officer and Chief Financial Officer of HUTCHMED, said: "This filing is an important step toward potentially bringing ORPATHYS plus TAGRISSO to patients in the US, after its approval in China based on the SACHI Phase III trial. The success of the global SAFFRON Phase III trial reflects the long-standing collaboration between HUTCHMED and AstraZeneca in addressing MET-driven progression in EGFR-mutated lung cancer. We remain committed to supporting the regulatory review and making this biomarker-directed, chemotherapy-free oral combination available to eligible patients."
ORPATHYS is being jointly developed by AstraZeneca and HUTCHMED and is commercialized by AstraZeneca.
About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death globally, accounting for almost one in four (23%) cancer deaths.[1] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC.[2] Approximately 75% of NSCLC patients are diagnosed with advanced disease.[3] Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFRm NSCLC.
MET is a tyrosine kinase receptor that has an essential role in normal cell development.[7] MET overexpression or amplification can lead to tumor growth and the metastatic progression of cancer cells.[7],[8] An estimated 34% of tumors will develop high levels of MET overexpression or amplification after progression on a third‑generation EGFR TKI.[1]
About SAFFRON
SAFFRON is a randomized, open-label, multi-center, global Phase III trial studying the efficacy of ORPATHYS (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 first- or second-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 endpoint includes OS.
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.
About ORPATHYS
ORPATHYS (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.
ORPATHYS 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. ORPATHYS also received a conditional approval in China for the treatment of adult patients with locally advanced or metastatic gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma patients with MET amplification who have failed at least two prior systemic treatments. ORPATHYS in combination with TAGRISSO is approved in China for patients with locally advanced or metastatic EGFR mutation-positive non-squamous NSCLC with MET amplification after disease progression on EGFR TKI therapy based on the SACHI Phase III trial. The combination was also 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. The global, randomized, SAFFRON Phase III trial in the same treatment setting comparing the combination with doublet platinum-based chemotherapy reported positive high-level results, demonstrating a statistically significant and clinically meaningful improvement in PFS and OS in August 2026.
About TAGRISSO
TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including the treatment of central nervous system metastases.
TAGRISSO is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for first-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 first-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.
(Press release, Hutchison China MediTech, SEP 28, 2026, View Source [SID1234671119])