Sunvozertinib (DZD9008) is a potent ErbBs and BTK inhibitor, with inhibitory effects on EGFR, Her2, and mutant epidermal growth factor. Sunvozertinib (DZD9008) showed inhibitory effects on EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutations, as well as Her2 exon 20 YVMA and EGFR WT A431 with IC50 of 20.4, 20.4, 1.1, 7.5, and 80.4 nM.

HER2 exon20 YVMA:7.5 nM, EGFR (L858R/T790M):1.1 nM, EGFR (exon 20 insertion):20.4 nM

METHODS: To test the cellular activity of Sunvozertinib (DZD9008) , 14 different EGFRexon20ins were engineered into the Ba/F3 cell line.
RESULTS In these cell lines, Sunvozertinib (DZD9008) showed potent pEGFR downregulation activity with IC50 ranging from 6 to 40 nM; in other cell lines expressing EGFR sensitive mutations, T790M resistance mutations, and rare mutations, Sunvozertinib (DZD9008) downregulated pEGFR more effectively with IC50 ranging from 1.1 to 12 nM; in the A431 cell line overexpressing wild-type EGFR, Sunvozertinib (DZD9008) was less potent in downregulating pEGFR with an IC50 of 58 nM. [1]

METHODS: Blood samples from the LU3075 PDX mouse model were collected at 0.5, 1, 2, 4, 8, and 24 hours after administration of sunvozertinib (DZD9008) (12.5, 25, and 50 mg/kg, orally, twice daily) on day 28 for LC/MS-MS analysis.
RESULTS Oral sunvozertinib (DZD9008) showed profound anti-tumor efficacy in a dose-dependent manner. [2]