Tislelizumab combined with donafenib and GEMOX as first-line treatment for advanced biliary tract cancer: A single-arm, phase II study.

4110 Background: Advanced biliary tract cancer (BTC) progresses rapidly and has a poor prognosis, with a 5-year survival rate of less than 5%. Gemcitabine and oxaliplatin (GEMOX) plus tislelizumab and donafenib as the first-line treatment for advanced BTC has confirmed good safety and preliminary efficacy in our phase I study (NCT04979663). This study aimed to further evaluate the efficacy and safety of GEMOX plus tislelizumab and donafenib. Methods: This is a single-arm, phase II trial (NCT05668884). Patients were enrolled if they were 18-75 years old, had stage III/IV cancer (AJCC 8th Edition), were Child-Pugh A/B, had an ECOG PS of 0-1, and had received no prior systemic therapy or tumor-related surgery. Patients were administrated with tislelizumab (200 mg IV on d1 Q3W), donafenib (200mg PO BID) and GEMOX (Q3W up to 8 cycles: gemcitabine 1000 mg/m² IV on d1 and 8, oxaliplatin 100 mg/m² IV on d1). Treatment continued until disease progression or unacceptable toxicity or withdrawal of consent whichever occurred first. The primary endpoint was the objective response rate (ORR) assessed by RECIST v1.1. Results: From December 2022 to October 2025, 47 patients were enrolled with a mean age of 60.8 (18 females and 29 males), 35 patients had intrahepatic cholangiocarcinoma, 11 patients had gallbladder carcinoma and 1 patient had perihilar cholangiocarcinoma. The ORR and the disease control rate (DCR) by RECIST 1.1 were 38.3% (18/47) and 93.6% (44/47), respectively. 2 patients underwent subsequent surgery after first-line treatment. The median PFS was 12.1 months (95%CI: 5.1-19.1), 1-year survival rate was 57% (95%CI: 38-76). All patients had treatment-related adverse events (TRAEs), the incidence of grade 3-4 TRAEs was 46.8%, the most common grade 3-4 TRAEs were rash (6/47,12.8%), thrombocytopenia (5/47,10.6 %) and fever (3/47, 6.4%). No grade 5 TRAEs were observed . Conclusions: GEMOX plus tislelizumab and donafenib as a first line treatment option for advanced BTC patients shows favorable efficacy and tolerability. Clinical trial information: NCT05668884 .