The U.S. Food and Drug Administration (FDA) has granted accelerated approval to zanidatamab-hrii (Ziihera), a bispecific HER2-directed antibody, for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA-approved test.
The FDA also approved Ventana PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody as a companion diagnostic device to aid in identifying patients with biliary tract cancer who may be eligible for treatment with zanidatamab.
Efficacy and Safety
Efficacy was evaluated in HERIZON-BTC-01 (ClinicalTrials.gov identifier NCT04466891), an open-label multicenter, single-arm trial in 62 patients with unresectable or metastatic HER2-positive (IHC3+) biliary tract cancer. Patients were required to have received at least one prior gemcitabine-containing regimen in the advanced-disease setting.
As determined by an independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1, the objective response rate was 52% (95% confidence interval [CI] = 39%–65%) and median duration of response was 14.9 months (95% CI = 7.4 to not estimable).
The prescribing information contains a boxed warning for embryofetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.
The recommended zanidatamab dose is 20 mg/kg administered as an intravenous infusion once every 2 weeks until disease progression or unacceptable toxicity.
Additional Regulatory Information
The FDA issued the approval of zanidatamab-hrii on November 20, 2024, and approved the companion diagnostic on November 21, 2024.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.
