Efficacy and safety of tislelizumab and apatinib combined with hepatic arterial infusion chemotherapy for advanced intrahepatic cholangiocarcinoma: A single-arm, phase 2 study.

Abstract

e16169 Background: Advanced intrahepatic cholangiocarcinoma (ICC) remains a highly aggressive malignancy with limited treatment options and poor prognosis. Systemic chemotherapy and immune therapies have shown modest efficacy, highlighting the need for novel combination strategies. This single-arm phase 2 study evaluated the efficacy and safety of tislelizumab (a PD-1 inhibitor) combined with apatinib (a VEGFR-2 inhibitor) and hepatic arterial infusion chemotherapy (HAIC) in patients with advanced ICC. Methods: Eligible patients with histologically confirmed advanced ICC were enrolled between Jan 2022 and Jun 2025. Treatment consisted of HAIC (oxaliplatin 130 mg/m²,5-Fu 400mg/ m², 5-Fu 1200mg/ m² via hepatic artery on day 1/2 each 3-week cycle), tislelizumab (200 mg intravenously every 3 weeks) and apatinib (250 mg orally daily). The primary endpoint was objective response rate (ORR) per RECIST v1.1, assessed by independent radiological review. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 17 patients were enrolled, with a median follow-up of 22 months. The confirmed ORR was 41.2% (95% CI: 18.4%-67.1%). The DCR was 88.3% (95% CI: 65.6%-98.5%). Median PFS was 8.8 months (95% CI: 4.33 - NA months), and the median OS was 17.6 months (95% CI: 15.0 - NA months). Notably, 3 of 17 patients (17.6%) subsequently underwent liver tumor resection with curative intent, achieving R0 resection. Eight patients (47.1%) had at least one any-grade treatment-related adverse event (TRAE); grade 3-4 TRAEs occurred in 3 patients (17.6%), with elevated transaminases (47.1%) being most common. No treatment-related deaths occurred. Conclusions: The combination of HAIC, tislelizumab and apatinib demonstrated promising efficacy with a manageable safety profile in advanced ICC, supporting further investigation in larger controlled trials.