An evaluation of zanidatamab, a novel, anti-HER2 biparatopic antibody, for the treatment of biliary tract cancer.

INTRODUCTION

Zanidatamab is a humanized biparatopic IgG antibody that selectively inhibits HER2 signaling pathway by targeting two distinct epitopes in the extracellular domains II and IV of HER2. Zanidatamab received accelerated approval from the United States Food and Drug Administration for the treatment of HER2-positive (immunohistochemistry [IHC] 3+) biliary tract cancer (BTC) in November 2024. Additionally, zanidatamab received approval for the treatment of HER2 IHC 3+ BTC from the European Medicines Agency in June 2025, and from National Medical Products Administration of China in May 2025.

AREAS COVERED: We review the currently available advanced BTC treatments from the perspective of targeted therapy, discuss the implications of HER2 as a therapeutic target in BTC, and discuss the available clinical trial data for zanidatamab for BTC treatment. We then comment on how zanidatamab can fit into the current standard of care for advanced BTC treatment, and the directions of future development strategies.

EXPERT OPINION: Zanidatamab appears to be effective for controlling disease progression and maintaining a durable response in patients with previously-treated unresectable or metastatic HER2-positive BTC, with acceptable safety profiles. Based on these favorable data, further investigations using zanidatamab as an earlier line of therapy for BTC are ongoing.