Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 384

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 384
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 the wild-type), weaker activity against other MET mutants and almost no activity against all other kinases. Savolitinib was found to be approximately 1,000 times more potent to MET than the next non-MET kinase. Similarly, in cell-based assays measuring activity against MET phosphorylation, savolitinib demonstrated potent activity in both ligand-independent (gene amplified) and ligand-dependent (overexpressed) cells with low IC50. In target related tumor cell function assays, savolitinib showed high potency with IC50 of less than 10 nM. Savolitinib demonstrated cytotoxicity only on tumor cells that were MET amplified or overexpressed. In other cells, IC50 amounts were over 30,000 nM, thousands of times higher than the IC50 on MET tumor cells.
The data above suggest that (i) savolitinib has potent activity against tumor cell lines with MET amplification in the absence of hepatocyte growth factor, or HGF, indicating that there is HGF-independent MET activation; (ii) savolitinib has potent activity in tumor cell lines with MET overexpressed, but only in the presence of HGF, indicating HGF-dependent MET activation; and (iii) savolitinib has no activity in tumor cell lines with low MET overexpression/ amplification, suggesting that strong kinase selectivity.
Savolitinib Clinical Development
Savolitinib Combination - Non-small Cell Lung Cancer

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Treatment                    Trial Name, Patient Focus                   Sites        Phase       Status/Plan                                  NCT #      
Savolitinib + Tagrisso   ​   SAVANNAH: 2L/3L EGFRm MET-              ​   Global   ​   II      ​   Fully enrolled in Feb 2024               ​   NCT03778229
​                        ​   amplified/overexpressed post Tagrisso   ​   ​        ​   ​       ​   Positive results announced in Oct 2024   ​   ​          
Savolitinib + Tagrisso   ​   SAFFRON: 2L/3L EGFRm MET-               ​   Global   ​   III     ​   Ongoing                                  ​   NCT05261399
​                        ​   amplified/overexpressed post Tagrisso   ​   ​        ​   ​       ​