altiratinib (DCC-2701)

Initial screening (300 drugs, including 33 MET-TKIs) was performed using Ba/F3 cells carrying METex14 plus MET D1228A/Y because anecdotal case reports suggested that D1228X mutations were more refractory to second-line MET-TKIs than Y1230X mutations.This screening found four candidate type II MET-TKIs (altiratinib, CEP-40783, foretinib and sitravatinib). We then performed further growth inhibitory assays using these four candidates plus other four MET-TKIs (type Ib; capmatinib and tepotinib, type II; cabozantinib and merestinib) in Ba/F3 cells carrying METex14 plus one of MET D1228A/E/G/H/N/V/Y or Y1230C/D/H/N/S secondary mutations... The type II MET-TKI foretinib may be an appropriate second-line MET-TKI for NSCLCs carrying METex14 after campatinib/tepotinib treatment failure by secondary mutations at D1228 or Y1230 residues.212

The type II MET-TKI foretinib may be an appropriate second-line treatment for NSCLCs carrying METex14 after campatinib/tepotinib treatment failure by secondary mutations at residue D1228 or Y1230.