Apatinib combined with adebrelimab and GEMOX regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: A multicenter, open-label, single-arm, phase II trial.

Abstract

e16202 Background: Immune checkpoint inhibitor combined with chemotherapy have shown improved prognosis compared with chemotherapy alone in patients with advanced intrahepatic cholangiocarcinoma (ICC). However, whether adding tyrosine kinase inhibitor (TKI) could further provide more survival benefits remains unclear. This study aims to evaluate the efficacy and safety of apatinib (a VEGFR2-targeted TKI) combined with adebrelimab (PD-L1 inhibitor) and GEMOX chemotherapy as first-line treatment for advanced ICC. Methods: This study (ACADEMY) enrolled adults aged ≤75 years with pathologically confirmed advanced ICC. All patients received apatinib (250 mg daily) combined with adebrelimab (1200 mg, day 1) and GEMOX chemotherapy (Gemcitabine 1000 mg/m 2 , day 1 and day 8; Oxaliplatin 85 mg/m 2 , day 1) per 21-day cycle. Tumor response was assessed using both RECIST 1.1 and mRECIST criteria. Survival outcomes were analyzed using Kaplan-Meier methods. The primary endpoint was objective response rate (ORR) accessed by RECIST 1.1 criteria. The secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR) and treatment-related adverse events (TRAEs). A Simon’s two -stage Optimum design was adopted in this study. If a response is observed in over 3 out of the initial 13 evaluated patients during the first phase, an additional 21 patients would be recruited for the study. Results: As of January 4, 2026, a total of 22 patients were recruited (median age 58.9 years; 59.1% female; 27.2% HBV-positive), with 19 included in efficacy analysis. Baseline characteristics: median tumor size 7.2 cm, median tumor number 3.5, 95.5% with TNM stage III-IV, 45.5% with macrovascular invasion. The ORR was 31.6% (RECIST 1.1) and 63.2% (mRECIST), and DCR was 100% (RECIST 1.1 and mRECIST criteria). With a median follow-up time of 7.9 months, the estimated median PFS was 6.2 months (95% CI: 5.4-NR), the 6-month OS rate was 100%, and the median OS was not reached. 21.1% (4/19) patients underwent radical surgical resection after tumor downstaging. In the respect of safety evaluation, TRAEs were observed in all enrolled patients, 50.0% with grade 3-4, and no grade 5 TRAE occurred. The most frequent AEs were hypoalbuminemia (68.2%), fatigue (59.1%) and liver damage (36.4%). Conclusions: Apatinib combined with adebrelimab and GEMOX regimen demonstrates promising efficacy and acceptable safety profile as first-line treatment for advanced ICC, supporting its potential as a preferred therapeutic option. Clinical trial information: NCT06925516 .