TAS-121 (TAS 121) is an orally available, potent, novel third-generation EGFR-TKI that selectively targets EGFR activating and T790M resistance mutations, sparing wild-type EGFR.
TAS-121 inhibited the L858R mutation and Ex19del mutation of EGFR with IC50 values of 1.7 and 2.7 nM, respectively.
TAS-121 also inhibited the L858R/T790M mutation and Ex19del/T790M mutation with IC50 values of 0.56 and 1.1 nM, inhibits wild-type EGFR with IC50 of 8.2 nM.
TAS-121 potently inhibited the growth of HCC827 cells (EGFR Ex19del) and NCI-H1975 cells (EGFR L858R, T790M), with IC50 values of 3.8 and 30 nM, respectively.
TAS-121 (50 and 100 mg/kg) showed potent dose-dependent activity against NCI-H1975 tumors, and regression of lesions in NCI-H1975 xenograft models, also showed antitumor activity in an HCC827 xenograft model at doses from 6.3 to 25 mg/kg.
TAS-121 (25 to 100 mg/kg) showed antitumor activity in an SW48 xenograft model harboring an EGFR G719S mutation.