FDA Approves Zanidatamab-hrii for HER2-Positive Biliary Tract Cancer

On November 20, 2024, the Food and Drug Administration (FDA) granted accelerated approval for the use of zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals, Inc.), a bispecific HER2-directed antibody. This approval is specifically for patients with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), which is confirmed through an FDA-approved diagnostic test.

Additionally, the FDA approved the VENTANA PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody, developed by Ventana Medical Systems, Inc./Roche Diagnostics. This antibody is to be used as a companion diagnostic tool to help identify BTC patients who may be suitable for treatment with Ziihera.

The efficacy of zanidatamab-hrii was assessed in a clinical trial named HERIZON-BTC-01 (NCT04466891). This was an open-label, multicenter, single-arm study that included 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. Before participating in the trial, patients had to have received at least one prior treatment regimen containing gemcitabine for advanced disease.

Key efficacy outcomes in the trial were measured by the objective response rate (ORR) and the duration of response (DOR), evaluated by an independent central review according to RECIST v1.1 criteria. Results showed an ORR of 52% (95% CI: 39, 65), with a median DOR of 14.9 months (95% CI: 7.4, not estimable).

The prescribing information for zanidatamab-hrii includes a boxed warning regarding embryo-fetal toxicity. Common adverse reactions, occurring in at least 20% of patients, included diarrhea, infusion-related reactions, abdominal pain, and fatigue. The recommended dosage for zanidatamab-hrii is 20 mg/kg, administered intravenously every two weeks until disease progression or the occurrence of unacceptable toxicity.

The FDA’s review of this application was facilitated by the Assessment Aid, a voluntary submission from the applicant to streamline the evaluation process. The application received priority review, breakthrough therapy designation, and orphan drug designation. These designations are part of the FDA’s expedited programs, which are designed to speed up the development and review of drugs intended to treat serious conditions.

Healthcare professionals are encouraged to report any serious adverse events associated with the use of zanidatamab-hrii to the FDA’s MedWatch Reporting System. The prescribing information for Ziihera will be available on the Drugs@FDA website. This approval represents a significant advancement for patients with HER2-positive biliary tract cancer, offering a new therapeutic option where few existed before.