Bispecific Antibody Regimen Approved for HER2-Positive Upper GI Cancers

The FDA approved zanidatamab (Ziihera) combined with tislelizumab and chemotherapy as first-line treatment for unresectable or metastatic HER2-positive gastroesophageal adenocarcinoma. The approval is based on the phase III HERIZON-GEA-01 trial, which showed about a 7-month improvement in overall survival and over 4 months in progression-free survival versus trastuzumab plus chemo. Two companion diagnostic tests were also approved to identify eligible patients.

The approval marks the first new first-line option for HER2-positive gastroesophageal adenocarcinoma in over a decade, building on zanidatamab’s earlier clearance in biliary tract cancers. The HERIZON-GEA-01 trial enrolled patients with advanced disease, and the benefit appeared independent of PD-L1 status, broadening the potential treatment population. Diarrhea was the most common side effect, with higher rates of severe events when tislelizumab was added. Two companion diagnostics were simultaneously cleared, ensuring HER2 testing aligns with the new regimen.

Clinicians have called the data practice-changing, noting that HER2-positive tumors represent roughly one-fifth of these cancers, which historically carry a poor prognosis. The regimen’s flexibility—allowing chemotherapy with or without the PD-1 inhibitor—offers tailoring based on patient tolerance and tumor characteristics, though the added immunotherapy increases toxicity risk.