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Ziihera + Tevimbra + chemotherapy is a combination regimen consisting of the HER2-targeted bispecific antibody zanidatamab (Ziihera), the PD-1 inhibitor tislelizumab (Tevimbra), and a fluoropyrimidine- and platinum-containing chemotherapy backbone. Developed by Jazz Pharmaceuticals, BeOne Medicines, and Zymeworks, this triplet regimen is indicated for the first-line treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction, and esophagus. Zanidatamab binds to two distinct non-overlapping epitopes on HER2 (ECD2 and ECD4), leading to receptor internalization, downregulation, and immune-mediated cytotoxicity (ADCC, ADCP, CDC). Tislelizumab is a monoclonal antibody that blocks PD-1, preventing its interaction with PD-L1 and PD-L2 to restore T-cell anti-tumor activity. In the Phase 3 HERIZON-GEA-01 trial, the combination demonstrated a significant overall survival benefit (median OS of 26.4 months vs. 19.2 months) and progression-free survival benefit (median PFS of 12.4 months vs. 8.1 months) compared to trastuzumab plus chemotherapy.
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