The China National Medical Products Administration (NMPA) has granted approval for the combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) to treat patients with locally advanced or metastatic EGFR mutation-positive non-squamous non-small cell lung cancer (NSCLC) with MET amplification after disease progression on EGFR tyrosine kinase inhibitor therapy. The approval, announced by HUTCHMED on June 30, 2025, represents a significant advancement in addressing treatment resistance in lung cancer patients.
Phase III SACHI Trial Results Drive Approval
The NMPA approval was based on compelling data from the SACHI Phase III trial (NCT05015608), which met its pre-defined primary endpoint of progression-free survival in a pre-planned interim analysis. In the intention-to-treat population, the ORPATHYS-TAGRISSO combination reduced the risk of disease progression by 66% compared to platinum-based chemotherapy, with a median progression-free survival of 8.2 months versus 4.5 months as assessed by investigators.
The independent review committee reported similarly impressive results, showing a 60% risk reduction in disease progression with a median progression-free survival of 7.2 months compared to 4.2 months for chemotherapy. Primary results were presented at the American Society of Clinical Oncology Annual Meeting in June 2025.
Safety Profile and Treatment Benefits
The safety profile of the combination therapy proved tolerable with no new safety signals observed. Treatment-emergent adverse events of Grade 3 or above occurred in 57% of patients in both the ORPATHYS plus TAGRISSO group and the chemotherapy group, suggesting a favorable safety profile comparable to standard chemotherapy.
Professor Shun Lu, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital and Principal Investigator of the SACHI trial, emphasized the clinical significance: "The approval of the ORPATHYS® and TAGRISSO® combination is a significant milestone in addressing the complex challenges of lung cancer treatment in China, where the EGFR mutation is common amongst NSCLC patients. For patients who develop MET amplification after progressing on EGFR inhibitors, the combination offers a continued all-oral, chemotherapy-free approach to tackle a critical resistance mechanism."
Addressing Treatment Resistance in Lung Cancer
The combination targets a critical resistance mechanism in EGFR-mutated NSCLC. Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. MET overexpression and amplification can lead to tumor growth and metastatic progression of cancer cells, representing one of the mechanisms of acquired resistance to EGFR TKI therapy.
ORPATHYS is an oral, potent and highly selective MET TKI that blocks atypical activation of the MET receptor tyrosine kinase pathway. TAGRISSO is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases.
Regulatory Recognition and Commercial Impact
The NMPA designated the combination as a Breakthrough Therapy in 2024 and granted the New Drug Application Priority Review status in 2025. This approval also triggers an $11 million milestone payment from AstraZeneca, which markets both drugs in China, to HUTCHMED.
Dr. Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, stated: "The NMPA approval marks an important step forward in our mission to address MET-driven progression following first-line EGFR-inhibitor therapy in NSCLC patients. Our collaboration with AstraZeneca, built on a shared vision to transform oncology care, has been crucial in reaching this achievement."
Global Development Strategy
This approval represents part of a broader global development strategy for the combination. The global SAFFRON Phase III trial is currently ongoing to assess the combination versus platinum-based doublet chemotherapy in patients with EGFR-mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following progression on TAGRISSO treatment. In 2023, the combination received Fast Track Designation from the US FDA for this indication.
Mary Guan, General Manager of AstraZeneca China Oncology Business, noted: "This milestone marks the third indication of ORPATHYS® approved in China, bringing a new treatment option to lung cancer patients who develop MET amplification after progressing on EGFR inhibitor therapy."
Clinical Context and Patient Impact
Lung cancer represents the leading cause of cancer death, accounting for about one-fifth of all cancer deaths globally. NSCLC comprises 80-85% of all lung cancer cases, with approximately 75% of patients diagnosed with advanced disease. In Asia, 30-40% of NSCLC patients have EGFR-mutated disease, making this approval particularly relevant for the Chinese patient population.
The combination represents the only all-oral treatment option for this specific patient population, offering a chemotherapy-free approach that maintains quality of life while addressing treatment resistance. TAGRISSO has been used to treat nearly 800,000 patients across its indications worldwide, with extensive evidence supporting its use as standard of care in EGFR-mutated NSCLC.
