FDA grants accelerated approval to zanidatamab-hrii for previously treated unresectable or metastatic HER2-positive biliary tract cancer
Regulatory approval news: The FDA granted accelerated approval (Nov 21, 2024) 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. Approval was supported by the single-arm HERIZON-BTC-01 trial (n=62), with ORR 52% and median DOR 14.9 months. FDA also approved the VENTANA PATHWAY anti-HER-2/neu (4B5) assay as a companion diagnostic.
FDA accelerated approval: zanidatamab-hrii in HER2-positive biliary tract cancer
Type: Regulatory approval (accelerated approval)
On November 21, 2024, the FDA granted accelerated approval to zanidatamab-hrii (Ziihera; Jazz Pharmaceuticals, Inc.), a bispecific HER2-directed antibody, for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.
The FDA also approved VENTANA PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic to help identify patients with BTC who may be eligible for Ziihera.
Supporting evidence
Efficacy was evaluated in HERIZON-BTC-01 (NCT04466891), an open-label, multicenter, single-arm trial of 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. Patients had received ≥1 prior gemcitabine-containing regimen in the advanced disease setting.
Primary outcome measures were ORR and DOR by independent central review (RECIST v1.1):
- ORR: 52% (95% CI, 39–65)
- Median DOR: 14.9 months (95% CI, 7.4–not estimable)
Safety and dosing (label)
The prescribing information includes a boxed warning for embryo-fetal toxicity. Common adverse reactions (≥20%) included diarrhea, infusion-related reactions, abdominal pain, and fatigue. Recommended dose: 20 mg/kg IV every 2 weeks until progression or unacceptable toxicity.
The application received priority review, breakthrough therapy designation, and orphan drug designation.