Ayvakit: animal efficacy model or human cells?

“Avapritinib also exhibited anti-tumor activity in a mouse mastocytoma tumor model with an activating KIT exon 17 mutation and in an imatinib-resistant patient-derived xenograft model of human GIST with activating KIT exon 11/exon17 mutations.”

“Although inhibition of PDGFRα exon 18 mutants by avapritinib at low nM concentrations has been demonstrated, the effect of avapritinib in PDGFRα driven in vivo animal tumour models have not been examined.”

“According to the ICH S9 Q&A document, the lack of in vivo characterization can be accepted if in vitro systems used for pharmacology studies of anti-tumour activity are demonstrated to generate relevant data. This is considered fulfilled in the non-clinical dossier for avapritinib.”