HUTCHMED and AstraZeneca submit a US FDA NDA for ORPATHYS plus TAGRISSO in MET-driven EGFR-mutated NSCLC following EGFR-TKI progression.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
HUTCHMED (China) announced that AstraZeneca has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ORPATHYS (savolitinib) in combination with TAGRISSO (osimertinib) for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET overexpression or amplification who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. The submission seeks to expand access to a biomarker-directed treatment option for patients with MET-driven resistance following EGFR-TKI treatment.
Addressing an Unmet Need in Resistant NSCLC
Lung cancer is the leading cause of cancer-related death worldwide and is broadly classified into NSCLC and small cell lung cancer. NSCLC accounts for approximately 80% to 85% of lung cancer cases. About 75% of patients are diagnosed with advanced-stage disease at presentation.
EGFR mutations are reported in approximately 10% to 15% of NSCLC patients in the U.S. and Europe and 30% to 40% of patients in Asia. MET is a receptor tyrosine kinase involved in normal cell growth and development.
MET overexpression or amplification can contribute to tumor growth and progression and occurs across multiple tumor types. Approximately 34% of tumors progressing on a third-generation EGFR TKI have been reported to develop high levels of MET overexpression or amplification. MET overexpression or amplification is also one of the most common mechanisms of resistance following third-generation EGFR-TKI treatment.
SAFFRON Phase III Trial
SAFFRON (NCT05261399) is a randomized, open-label, global Phase III trial evaluating savolitinib plus osimertinib in adults with EGFR-mutated, MET-overexpressed and/or MET-amplified, locally advanced or metastatic NSCLC that progressed following first- or second-line osimertinib treatment.
The trial enrolled 338 patients across 230 centers in 29 countries. Patients received either ORPATHYS 300 mg twice daily in combination with TAGRISSO 80 mg once daily or platinum-based doublet chemotherapy.
Progression-free survival (PFS) was the primary endpoint, with overall survival (OS) among the key secondary endpoints.
Key Efficacy and Safety Results
Topline results from SAFFRON demonstrated statistically significant and clinically meaningful improvements in both PFS and OS with savolitinib plus osimertinib compared with platinum-based doublet chemotherapy.
The safety profile of the combination was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified.
The SAFFRON findings build on earlier clinical development of savolitinib plus osimertinib in MET-driven, EGFR-mutated NSCLC, including the Phase III SACHI study.
China Approval and U.S. Regulatory Submission
ORPATHYS in combination with TAGRISSO was approved in China in June 2025 based on results from the Phase III SACHI trial. The approved indication covers patients with locally advanced or metastatic EGFR mutation-positive non-squamous NSCLC with MET amplification who have progressed on an EGFR TKI following initial first-line treatment.
The U.S. NDA is based on the SAFFRON Phase III results and seeks approval for patients with locally advanced or metastatic NSCLC with MET overexpression or amplification following progression on or after EGFR-TKI therapy.
Path Forward
The U.S. NDA submission represents the next regulatory step for the ORPATHYS and TAGRISSO combination in MET-driven, EGFR-mutated NSCLC. If approved, the combination would provide a biomarker-directed treatment option for patients whose disease has progressed following EGFR-TKI therapy.
The full SAFFRON results will be presented in a Presidential Symposium at the upcoming ESMO Congress 2026.
Reference
HUTCHMED Announces Submission of US NDA for ORPATHYS® plus TAGRISSO® in MET-Driven EGFR-Mutated Lung Cancer, HUTCHMED, 29 September 2026
Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment (SAFFRON), ClinicalTrials.gov ID NCT05261399
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.