Savolitinib Plus TAGRISSO® Shows 56% Response Rate in MET-High Lung Cancer, HUTCHMED Reports
核心洞察
SAVANNAH Phase II trial demonstrated high and durable response rates with savolitinib plus TAGRISSO® in patients with EGFRm NSCLC (搜索) with MET overexpression/amplification who progressed on first-line TAGRISSO®.
Long-term survival benefits were observed in a Phase IIIb study of savolitinib in MET exon 14 skipping NSCLC (搜索), with treatment-naïve patients achieving a median overall survival of 28.3 months.
The combination represents a promising chemotherapy-free oral treatment strategy to address resistance mechanisms in advanced NSCLC (搜索), with savolitinib and TAGRISSO® having received FDA Fast Track Designation in 2023.
The SAVANNAH Phase II trial has demonstrated impressive efficacy for the combination of savolitinib plus TAGRISSO® (osimertinib) in patients with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (搜索) (NSCLC (搜索)) with high levels of MET overexpression and/or amplification whose disease progressed on first-line TAGRISSO® treatment.
According to data presented by HUTCHMED at the European Lung Cancer (搜索) Congress (ELCC) 2025, the combination therapy showed a confirmed objective response rate (ORR) of 56% (95% CI: 45%–67%) by investigator assessment and 55% (95% CI: 43%–66%) by blinded independent central review (BICR).
The duration of response (DoR) was 7.1 months (95% CI: 5.6–9.6) and 9.9 months (95% CI: 6.0–13.7) by investigator and BICR assessment, respectively. Median progression-free survival (PFS) reached 7.4 months (95% CI: 5.5–7.6) by investigator assessment and 7.5 months (95% CI: 6.4–11.3) by BICR.
Safety Profile Consistent with Established Data
Safety results from the SAVANNAH trial were consistent with the established profiles of each medicine, with no new safety concerns reported. In patients treated with savolitinib (300mg twice daily) plus TAGRISSO®, Grade 3 or higher adverse events (AEs) occurred in 57% of patients, while Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 32% of patients.
Dr. Myung-Ju Ahn from Samsung Medical Center, Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, presented these findings at ELCC 2025, which is taking place March 26-29 in Paris, France.
Long-term Survival Benefits in METex14 NSCLC
In a separate presentation, updated results from a Phase IIIb study of savolitinib in China demonstrated significant survival benefits and long-term safety in NSCLC (搜索) patients with MET exon 14 skipping alteration (搜索), particularly in treatment-naïve patients.
Among 166 patients who received savolitinib treatment, the median follow-up for 87 treatment-naïve patients was 34.5 months, while for 79 previously treated patients it was 25.1 months. Treatment-naïve patients achieved a median overall survival (OS) of 28.3 months (95% CI: 17.5–not evaluable), with a 36-month OS rate of 44.7%. Previously treated patients had a median OS of 25.3 months (95% CI: 20.5–30.5), with a 24-month OS rate of 51.7%.
Notably, patients with baseline brain metastasis also showed survival benefits, with median OS of 15.3 months in treatment-naïve patients with brain metastasis and 25.3 months in previously treated patients with brain metastasis.
Addressing a Significant Unmet Need
Lung cancer (搜索) remains the leading cause of cancer death globally, accounting for approximately one-fifth of all cancer deaths. NSCLC (搜索) represents about 80% of all lung cancer cases. While EGFR (搜索) tyrosine kinase inhibitors (TKIs) have improved outcomes in the first-line setting, treatment resistance and disease progression are common challenges.
"These results represent a significant advancement in addressing the unmet need for effective and well-tolerated treatment options in later-line settings for NSCLC (搜索) patients," said Dr. Yongfeng Yu from Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, who presented the Phase IIIb data.
The SAVANNAH trial enrolled over 360 patients across more than 80 centers globally, including sites in North America, Europe, South America, and Asia. The primary endpoint was ORR, with key secondary endpoints including PFS and DoR.
Regulatory Status and Ongoing Development
Savolitinib, an oral, potent, and highly selective MET tyrosine kinase inhibitor, is being jointly developed and commercialized by AstraZeneca and HUTCHMED. In 2023, the combination of savolitinib and TAGRISSO® received Fast Track Designation from the US Food and Drug Administration (FDA) for the treatment of patients with EGFRm NSCLC (搜索) with MET overexpression and/or amplification following progression on TAGRISSO®.
Savolitinib is already approved in China under the brand name ORPATHYS (搜索)® for the treatment of adult patients with locally advanced or metastatic NSCLC (搜索) with MET exon 14 skipping alteration (搜索). It has been included in the National Reimbursement Drug List of China since March 2023.
The global SAFFRON Phase III trial is currently ongoing to further assess the savolitinib plus TAGRISSO® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC (搜索) following TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in the SAVANNAH trial.
Mechanism of Action
MET is a tyrosine kinase receptor with an essential role in normal cell development. Savolitinib blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs due to mutations (such as exon 14 skipping alterations), gene amplification, or protein overexpression.
MET overexpression and/or amplification can lead to tumor growth and metastatic progression of cancer cells and is a known mechanism of acquired resistance to EGFR (搜索) TKIs. The combination of savolitinib with TAGRISSO® represents a promising chemotherapy-free oral treatment strategy to address these resistance mechanisms in advanced NSCLC (搜索).
HUTCHMED is also exploring other compounds, including surufatinib, which showed durable survival benefits as maintenance therapy following first-line chemo-immunotherapy in patients with extensive-stage small cell lung cancer (搜索) in an exploratory study presented at ELCC 2025.