Novel HER2-targeted Bispecific Antibody for Biliary Tract Cancer
The FDA granted accelerated approval to the first-in-class HER2-directed bispecific antibody zanidatamab-hrii.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to zanidatamab-hrii (Ziihera) for previously treated, unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.
The FDA concurrently expanded the approval of a companion diagnostic test for HER2 that can be used to determine eligibility for zanidatamab-hrii.
Zanidatamab-hrii is a type of targeted therapeutic called a bispecific antibody. It binds to HER2 in two different places, unlike most other HER2-targeting therapeutics, which only bind to a single site. This may help boost its efficacy compared to other HER2-targeting strategies.
This is the first FDA approval for zanidatamab-hrii. Zanidatamab-hrii is also the first HER2-targeting bispecific antibody and the first HER2-targeting treatment for biliary tract cancer to be approved by the FDA.
The approval was based on results from the open-label, multicenter, single-arm phase II HERIZON-BTC-01 clinical trial. Zanidatamab-hrii was given to 62 patients with unresectable or metastatic HER2-positive biliary tract cancer who had previously received at least one regimen containing the chemotherapeutic gemcitabine to treat their advanced cancer.
Overall, 52% of patients had a response to zanidatamab-hrii. Those who experienced a response had responses lasting a median of 14.9 months.
The recommended dose of zanidatamab-hrii is 20 mg/kg of body weight given as an intravenous infusion every two weeks until disease progression or unacceptable toxicity.
The prescribing information for zanidatamab-hrii contains a boxed warning for embryo-fetal toxicity.
Biliary tract cancers form in the gallbladder, in the ampulla of Vater (a duct located in the small intestine), or in the ducts that move bile, a key digestive enzyme, to and throughout the liver. Around 15% of biliary tract cancers are HER2-positive. According to federal statistics, it was estimated that 12,350 individuals would be diagnosed with biliary tract cancers and 4,530 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on November 20, 2024. Accelerated approval means that continued approval may be contingent upon a confirmatory trial. Please check this FDA web page for information about any accelerated approvals in oncology that may have been subsequently withdrawn and are no longer FDA-approved. Check this resource for updated information on all therapeutics regulated by the FDA.
