Zanidatamab Combined With Liposomal Irinotecan and Capecitabine for Second-line Treatment of HER2-positive Unresectable Biliary Tract Tumors

This is a prospective, multicenter, single-arm, phase II clinical study designed to explore the efficacy and safety of zanidatamab in combination with liposomal irinotecan and capecitabine as second-line therapy for HER2-positive advanced biliary tract cancer. Fifteen patients with unresectable locally advanced or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer, will be enrolled after progression on or intolerance to first-line therapy. HER2 positivity must be confirmed by immunohistochemistry and/or fluorescence in situ hybridization, defined as IHC 3+ or IHC 2+ with FISH-confirmed amplification. Zanidatamab 20 mg/kg will be administered intravenously on Day 1 every 2 weeks; liposomal irinotecan 50 mg/m² will be administered intravenously over 90 minutes on Day 2 every 2 weeks; and capecitabine 1,000 mg/m² will be administered orally twice daily on Days 1-10 of each 14-day cycle. Chemotherapy will be administered for a maximum of six cycles, and study treatment will continue until disease progression or unacceptable toxicity. The primary endpoint is objective response rate, as assessed according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, and safety.