The U.S. Food and Drug Administration (FDA) gave Ziihera® (zanidatamab-hrii) expedited approval on November 20, 2024, for the treatment of people with HER2-positive (IHC 3+) biliary tract carcinoma (BTC) that has already been treated but is incurable or metastatic. The first dual HER2-targeted bispecific antibody treatment for this patient population is now available.

Data from the Phase 2b HERIZON-BTC-01 trial, which assessed zanidatamab as a monotherapy in patients with HER2-positive BTC, served as the foundation for the FDA’s ruling. 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC participated in an open-label, multicenter, single-arm trial to assess efficacy. In the context of advanced disease, patients had to have undergone at least one previous gemcitabine-containing therapy. Objective response rate (ORR) and duration of response (DOR), as established by an independent central review in accordance with RECIST v1.1, were the primary efficacy outcome measures. The median DOR was 14.9 months (95% CI: 7.4, not estimable), and the ORR was 52% (95% CI: 39, 65).

Ziihera is act on two extracellular locations on the HER2 protein which are bound by the bispecific HER2-directed antibody ziihera. The internalization and decrease of HER2 receptors on the tumor cell surface are the results of this dual binding. Furthermore, zanidatamab-hrii inhibits tumor growth and causes cell death via inducing complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis. A boxed warning for embryo-fetal harm is included in the prescribing information. At least 20% of patients who received zanidatamab-hrii had diarrhea, infusion-related responses, lethargy, and abdominal discomfort as the most frequent side events.

An intravenous infusion of 20 mg/kg of zanidatamab-hrii is advised once every two weeks until the condition worsens or the toxicity becomes intolerable.

On disease front, biliary tract carcinoma” (BTC) describes a class of uncommon but deadly malignancies that develop in the gallbladder, ampulla of Vater, or bile ducts. The biliary system, which includes these organs, is in charge of moving bile from the liver to the small intestine to facilitate digestion.

This application was granted as priority review, breakthrough therapy designation, and orphan drug designation.