The FDA has granted accelerated approval to zanidatamab (Ziihera) for the treatment of adult patients with previously treated, unresectable or metastatic HER2-positive (immunohistochemistry 3+) biliary tract cancer. This regulatory decision, announced on November 20, 2024, is based on the promising results from the phase 2b HERIZON-BTC-01 trial (NCT04466891).
The HERIZON-BTC-01 trial enrolled patients with HER2-amplified, locally advanced unresectable or metastatic biliary tract cancer (including gallbladder cancer or intra-/extra-hepatic cholangiocarcinoma) who had received prior gemcitabine-containing therapy. The study involved 62 patients who were administered intravenous zanidatamab at a dose of 20 mg/kg every 2 weeks. The results demonstrated an overall response rate of 52% (95% CI, 39%-65%). The estimated median duration of response in this population was 14.9 months (95% CI, 7.4-not estimable).
Safety and Tolerability
The safety profile of zanidatamab was evaluated in 80 patients. Common adverse effects (AEs) included diarrhea, infusion-related reactions, abdominal pain, and fatigue. Serious AEs occurred in 53% of the safety-evaluable patients, with the most common being biliary obstruction (15%), sepsis (8%), biliary tract infection (8%), pneumonia (5%), gastric obstruction (3.8%), diarrhea (3.8%), and fatigue (2.5%).
Ongoing Confirmatory Trial
A confirmatory phase 3 trial, HERIZON-BTC-302 (NCT06282575), is currently underway. This trial is investigating zanidatamab plus standard-of-care (SOC) therapy compared with SOC therapy alone in the frontline setting for patients with HER2-positive biliary tract cancer.
Expert Commentary
According to James J. Harding, MD, associate attending physician at Memorial Sloan Kettering Cancer Center, "[This approval] offers a new treatment option for patients with [a] very difficult disease that has notable antitumor activity and…associated safety and tolerability."
Significance of Approval
This accelerated approval marks a significant advancement in the treatment landscape for patients with HER2-positive biliary tract cancer. Zanidatamab, a HER2-directed bispecific antibody, is the first HER2-targeted agent to receive accelerated approval for this disease, addressing a historically unmet medical need.
