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zanidatamab + tucatinib
- Development stage
- Unknown
- Lead developer
- Jazz Pharmaceuticals
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Zanidatamab + tucatinib is an investigational combination therapy comprising zanidatamab, a bispecific anti-HER2 monoclonal antibody, and tucatinib, a selective small molecule HER2 tyrosine kinase inhibitor. Zanidatamab acts by binding simultaneously to two non-overlapping extracellular domains on the HER2 receptor (ECD4 and ECD2), leading to inhibition of HER2 signaling, receptor internalization, and immune cell-mediated cytotoxicity, specifically antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP)[1]. Tucatinib selectively inhibits the tyrosine kinase domain of the HER2 receptor, blocking downstream PI3K and MAPK signaling, reducing cancer cell proliferation and survival[2][5]. The combination aims to enhance efficacy in HER2-overexpressing tumors, especially HER2-positive breast and gastroesophageal cancers, and is currently being evaluated in clinical trials for HER2-positive breast cancer[4].
- Other names
- zanidatamab + tucatinib
02
Targets
UGT (UDP-glucuronosyltransferase family)ERBB2 (Erb-b2 receptor tyrosine kinase 2)
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