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zanidatamab + chemotherapy + tislelizumab
- Development stage
- Unknown
- Lead developer
- Jazz Pharmaceuticals
- Modality
- Bispecific Antibodies → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics, Small Molecules, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
Zanidatamab + chemotherapy + tislelizumab is a combination therapy being evaluated for the first-line treatment of HER2-positive advanced or metastatic gastroesophageal adenocarcinoma (GEA). Zanidatamab is a biparatopic bispecific antibody that simultaneously binds to two non-overlapping extracellular domains of HER2 (ECD2 and ECD4), leading to dual blockade of HER2 signaling, increased receptor internalization, and enhanced antibody-dependent cellular cytotoxicity (ADCC). Tislelizumab is a humanized IgG4 monoclonal antibody directed against the PD-1 receptor, designed to minimize binding to Fcγ receptors on macrophages to avoid antibody-dependent cellular phagocytosis (ADCP) of T cells. The standard-of-care chemotherapy component typically consists of capecitabine and oxaliplatin (CAPOX) or 5-fluorouracil and cisplatin (FP). This triplet regimen, studied in the Phase 3 HERIZON-GEA-01 trial, aims to combine HER2-targeted therapy, immune checkpoint inhibition, and cytotoxic chemotherapy to improve survival outcomes in patients with HER2-overexpressing GEA.
- Other names
- zanidatamab-hrii
02
Targets
PDCD1 (Programmed cell death protein 1 receptor)ERBB2 (Erb-b2 receptor tyrosine kinase 2)DNATS (Thymidylate synthase)
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