Multinational phase 2b trial of zanidatamab for HER2-positive metastatic biliary tract cancer: final results from HERIZON-BTC-01

The multinational phase 2b HERIZON-BTC-01 trial evaluated the dual HER2-targeted bispecific antibody zanidatamab for HER2-positive (IHC 3+ or IHC 2+) metastatic biliary tract cancer (BTC) with disease progression with or following gemcitabine therapy. Final results have now been published. The trial included 80 patients (56% female; median age 64 years). The median follow-up was 33.4 months (range 28.0-45.0). The confirmed objective response rate by independent central review was 41.3% (95% CI 30.4-52.8), the median duration of response was 14.9 months (7.4-24.0), and the median overall survival was 15.5 months (10.4-18.7). At the time of best overall response, zanidatamab responders had reduced worst pain scores. Overall, 76% of patients experienced one or more treatment-related adverse event. Grade 3 TRAEs occurring in more than two patients were diarrhea (5.0%), decreased ejection fraction (3.9%), and anemia (3.8%). There were no treatment-related deaths. Two patients (3%) discontinued zanidatamab due to TRAEs. The authors conclude that zanidatamab demonstrated clinically meaningful benefit for patients with HER2-positive metastatic BTC.