Dr Vogel on the European Commission’s Marketing Authorization of Zanidatamab for HER2+ Biliary Tract Cancer

"The outcome with zanidatamab compared with what we have seen with chemotherapy was really good."

Arndt Vogel, MD, of the University of Toronto Institute of Medical Science, the Toronto General Hospital Research Institute, and the UHN-Princess Margaret Cancer Centre, discussed the clinical significance of the European Commission’s (EC) July 2025 marketing authorization of zanidatamab (Ziihera), a HER2-targeted bispecific antibody, for the treatment of patients with previously treated, unresectable, locally advanced or metastatic HER2-positive biliary tract cancer.

This decision marks a therapeutic advancement in a molecularly defined biliary tract cancer subgroup with historically limited treatment options and poor survival outcomes, Vogel began. Biliary tract cancer, including cholangiocarcinoma, is characterized by high recurrence rates and a poor prognosis, even following curative-intent surgery, according to Vogel. In the advanced setting, systemic therapy options remain limited, he said. Second-line chemotherapy regimens yield low objective response rates (ORR; ~ 6%), a median progression-free survival of approximately 3 months, and median overall survival (OS) of approximately 12 months, he explained.

Zanidatamab’s marketing authorization approval is supported by results from the phase 2b HERIZON-BTC-01 trial (NCT04466891), the largest study to date specifically evaluating HER2-targeted therapy in this population. The trial enrolled 87 patients, including 80 in cohort 1 with centrally confirmed HER2-positive tumors (immunohistochemistry [IHC] 2+/in situ hybridization–positive [ISH+], n = 18; IHC 3+/ISH+, n = 62). The trial met its primary end point, with patients who received zanidatamab achieving a confirmed ORR (cORR) of 41.3% (95% CI, 30.4-52.8) per independent central review at a median follow-up of 21.9 months. The median duration of response (DOR) was 14.9 months (95% CI, 7.4-not reached), and the median OS was 15.5 months (95% CI, 10.4-18.5).

A prespecified subgroup analysis in patients with IHC 3+ tumors showed further benefit with zanidatamab, with a cORR of 51.6% (95% CI, 38.6-64.5), a median DOR of 14.9 months (95% CI, 7.4-24.0), and median OS of 18.1 months (95% CI, 12.2-22.9).

Vogel emphasized that the EC’s decision affirms the growing role of biomarker-driven therapies in biliary tract cancer and supports the broader use of comprehensive genomic profiling to identify candidates for targeted treatment.