Zipalertinib

Zipalertinib, also known as TAS6417, CLN-081, is a Novel EGFR Inhibitor Targeting Exon 20 Insertion Mutations. TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model.