Zongertinib — Investigational Agent
EGFR Inhibitor · Phase 2/3 · Boehringer Ingelheim
Mechanism of Action
Zongertinib is a potent and highly selective oral tyrosine kinase inhibitor that targets the kinase domain of HER2 while sparing wild-type EGFR. It binds covalently to the ATP-binding site of both wild-type HER2 and various HER2 mutations, including exon 20 insertions. By inhibiting HER2 phosphorylation, it disrupts downstream signaling pathways such as MAPK and PI3K/AKT, leading to cell cycle arrest and apoptosis in HER2-dependent tumor cells. Its selectivity profile is designed to minimize EGFR-related toxicities like rash and diarrhea.
Investigational Indications
- HER2-mutant non-small cell lung cancer
- HER2-amplified solid tumors