A phase II trial evaluating liposomal irinotecan combined with capecitabine as second-line therapy for biliary tract cancer.

Abstract

e16261 Background: Gemcitabine plus cisplatin remains the standard first-line therapy for advanced biliary tract cancers (BTCs). However, disease progression within 8 months in most patients underscores the critical unmet need for effective second-line therapies. Compared to traditional irinotecan, the liposomal irinotecan offers a superior therapeutic profile characterized by higher efficacy and lower toxicity. The combination of liposomes irinotecan with capecitabine(a standard treatment) is currently being explored as a novel therapeutic option in ongoing clinical studies. Methods: This multicenter, single-arm, phase II trial enrolled patients with advanced BTCs (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer) who had progressed on first-line gemcitabine-based therapy. Patients received the combination of liposomal irinotecan and capecitabine. Treatment continued until disease progression. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS) and safety. Results: Between April 2024 and November 2025, 20 patients were enrolled and treated. The median age was 62.5 years (51-74), and 65% were male (13/20). Tumor types included extrahepatic cholangiocarcinoma (20%), intrahepatic cholangiocarcinoma (40%), and gallbladder cancer (40%). The combination therapy demonstrated promising efficacy, with a median PFS (mPFS) of 5.5 months（95%CI [4.50-NA]）. And the longest duration of continuous treatment observed was 14.1 months. which compares favorably to historical benchmarks in this setting. Of the 14 evaluable patients, 3 (21.4%) achieved a partial response, 8 (57.2%) maintained stable disease, and 3 (21.4%) experienced progressive disease. The ORR was 21.4%. Treatment was well-tolerated, with a 30% incidence of grade≥3 treatment-related adverse events (TRAEs). Including decreased white blood cell count(5.0%), neutropenia(10.0%) and diarrhea(5.0%). No fatal TRAEs were observed. Conclusions: The regimen of liposomal irinotecan plus capecitabine showed encouraging anti-tumor activity with a manageable safety profile in patients with gemcitabine-pretreated advanced BTCs, suggesting a potential new therapeutic option for the second-line setting. The follow-up work on patient survival is underway, and more data will be disclosed in the future. Clinical trial information: NCT06430827 .