Hepatic arterial infusion chemotherapy combined with immunotherapy for unresectable intrahepatic cholangiocarcinoma: A single-arm, open-label, prospective clinical trial.

2600 Background: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical advances in the treatment of intrahepatic cholangiocarcinoma (ICC). However, the efficacy of first-line systemic chemotherapy remains suboptimal for patients with unresectable ICC. Hepatic arterial infusion chemotherapy (HAIC) can markedly elevate local drug exposure, enhance tumor cytotoxicity, and minimize systemic adverse effects. Whether the combination of HAIC and immunotherapy confers a clinical benefit for patients with unresectable ICC remains an urgent clinical issue to be addressed. Methods: This is a single-arm, open-label, prospective clinical trial designed to evaluate the efficacy and safety of HAIC combined with ICIs in the treatment of patients with unresectable ICC. The HAIC regimen consists of gemcitabine plus cisplatin (GC-HAIC), while programmed death-1 (PD-1) inhibitors are administered for immunotherapy, with either camrelizumab or sintilizumab chosen on a patient clinical characteristics basis. The trial was planned to enroll 30 participants. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). Safety was assessed through the monitoring and grading of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Results: From August 2022 to January 2025, a total of 31 patients with unresectable ICC were enrolled and received the protocol-defined treatment. The ORR was 41.9% according to RECIST 1.1 criteria, while the ORR assessed per mRECIST criteria was 71%. The median follow-up time was 22.0 months (95% CI, 17.9–26.7 months). The median OS was 20.0 months (95% CI, 15.7–28.6 months), and the median PFS was 12.3 months (95% CI, 10.9–21.3 months). The DCR reached 93.5%. Treatment-related AEs of any grade occurred in 83.9% of patients, whereas grade 3 or 4 AEs were observed in only 16.1% of participants. Conclusions: This study evaluated the efficacy and safety of GC-HAIC combined with anti-PD-1 immunotherapy in the treatment of patients with unresectable ICC. The results demonstrated that this regimen exhibited promising efficacy, with manageable adverse events and complications. Additionally, these results also offer a potential novel first-line treatment option for this patient population. Based on the results of this study, future phase III clinical trails are warranted to validate the outcomes. Clinical trial information: ChiCTR2500112123. Tumor response. Efficacy RECIST 1.1 mRECIST % N % N CR 0 0 3 9.7 PR 13 41.9 19 61.3 SD 16 52.6 7 22.6 PD 2 6.5 2 6.5 ORR 13 41.9 22 71.0 DCR 29 93.5 29 93.5 CR, Complete response; PR, Partial response; SD, Stable disease; PD, Progressive disease; ORR, Objective response rate; DCR, Disease control rate.