Hepatic arterial infusion chemotherapy plus immune checkpoint inhibitors and lenvatinib for locally advanced biliary tract cancer: A single-arm, exploratory study.

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Background: Immune checkpoint inhibitors (ICIs) plus gemcitabine and cisplatin (GemCis) have become a standard first-line systemic treatment for advanced biliary tract cancers (BTCs). However, prognosis remains limited. Hepatic arterial infusion chemotherapy (HAIC) delivers high concentrations of cytotoxic agents directly to tumors, providing improved locoregional control, particularly in patients intolerant of systemic chemotherapy. In this prospective clinical study, we evaluated the preliminary clinical efficacy and safety of GemCis-HAIC plus ICIs and lenvatinib in patients with locally advanced BTCs. Methods: Eligible patients had locally advanced BTCs, with tumor lesions confined to the abdominal cavity, and were intolerant of or refused intravenous systemic chemotherapy. All patients received ICIs and lenvatinib plus GemCis-HAIC for up to six cycles according to response and tolerability. The primary endpoint was objective response rate (ORR). Results: As of December 2025, 10 patients were enrolled. The median age was 68 years (range, 36–71), with intrahepatic cholangiocarcinoma (iCCA) in 4 patients, perihilar cholangiocarcinoma (pCCA) in 5, and gallbladder cancer (GBC) in 1; At baseline, 30% had extrahepatic metastases, 80% had multifocal disease, and 30% had chronic viral hepatitis (HBV/HCV). Regarding treatment exposure, 70% of patients received ≥4 cycles of HAIC. ICIs included camrelizumab (n=5), adebrelimab (n=3), and durvalumab (n=2). Among 8 patients evaluable for response, 3 patients achieved partial response, 4 patients had stable disease, including 1 successfully converted to surgical resection, and 1 had progressive disease, yielding an ORR of 37.5% and a DCR of 87.5%. The median PFS was 5.29 months (95% CI, 2.34-8.24). Overall, 60% of patients experienced treatment-related adverse events (TRAEs), and grade 3 TRAEs occurred in 30% of patients, mainly elevated γ-glutamyl transferase (GGT). Conclusions: GemCis-HAIC plus ICIs and Lenvatinib showed promising antitumor activity with manageable toxicity in patients with BTCs. This regimen warrants further investigation as a potential first-line option in this population. Clinical trial information: ChiCTR2400091470 .