Zanidatamab Shows Promise for HER2-Positive, Unresectable Biliary Tract Cancer

According to a phase 2b study, zanidatamab, a bispecific antibody targeting 2 distinct HER2 epitopes, demonstrated meaningful clinical benefit with a manageable safety profile among patients with refractory, HER2-positive unresectable, locally advanced or metastatic biliary tract cancer.

The global, single-arm, HERIZON-BTC-01 trial enrolled 87 patients with HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer who had progressed on or after gemcitabine-based therapy. Patients were classified into cohorts based on HER2 immunohistochemistry score (IHC), with patients in Cohort 1 having an IHC 2+ or 3+ (n = 80; HER2-positive), and patients in Cohort 2 having an IHC 0 or 1+ (n = 7). All patients received 20 mg/kg zanidatamab intravenously every 2 weeks. The primary end point was confirmed objective response rate in Cohort 1, with antitumor activity and safety assessed in all participations.

At the time of data cutoff, the median duration of follow-up was 12.4 months. The confirmed objective response rate, as assessed by independent central review, was 41.3% (n = 33) in cohort 1.

Of all patients, there were 18% who experienced a grade 3 treatment-related adverse events. The most common of those events were diarrhea (5%) and decreased ejection fraction (3%). There were no grade 4 treatment-related adverse events, and no treatment-related deaths.

According to Dr Harding et al “these results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer.”

Source:
Harding JJ, Fan J, Oh DY, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): A multicentre, single-arm, phase 2b study. Lancet Oncol. Published on June 2, 2023. doi:10.1016/S1470-2045(23)00242-5