HERIZON-BTC-01

NCT04466891 📎

Regimen

Experimental
Zanidatamab 20 mg/kg IV every 2 weeks (bispecific antibody targeting two non-overlapping HER2 epitopes — both domain 2 and domain 4)
Control
single-arm / no comparator

Population

Previously treated (≥1 prior therapy) unresectable or metastatic BTC with HER2 amplification by central IHC/ISH (IHC 3+ or IHC 2+/ISH+); all BTC subtypes enrolled: GBC (~40%), ICC (~35%), ECC (~25%). HER2 amplification highest in GBC (~20-30%) vs lower ICC/ECC rates. Median 2 prior lines.

Key finding

Zanidatamab received FDA accelerated approval in August 2024 for previously treated HER2-amplified BTC, making HER2 the third approved biomarker target in this disease (after FGFR2 and IDH1). The bispecific mechanism (simultaneous HER2 domain 2 + domain 4 engagement) induces receptor clustering, internalization, and ADCC — conceptually distinct from single-agent trastuzumab. ORR 41.3% with durable median DoR of 12.9 months is clinically meaningful in the 2L+ setting. Tolerability favorable: diarrhea (45%) was the most common treatment-related adverse event.

Source: PMID 37276871

Timeline

    Guideline citations

    • NCCN BTC (p.6)