Combined therapy using gemcitabine and cisplatin chemotherapy, lenvatinib, and adebrelimab for patients with advanced and unresectable intrahepatic cholangiocarcinoma: A prospective, single-arm, phase II trial.

Abstract

e16190 Background: The prognosis of advanced intrahepatic cholangiocarcinoma (ICC) remains unsatisfactory with current gemcitabine-based chemotherapy in combination with PD-1/PD-L1 inhibitors. This study aimed to investigate the efficacy and safety of aderbrelimab (PD-L1 inhibitor) and lenvatinib in combination with gemcitabine and cisplatin as first-line treatment in advanced and unresectable ICC patients. Methods: This prospective, single-arm, multicenter, phase II study included treatment-naive adult (≥18 years) patients with unresectable and advanced ICC. All patients received 1200mg aderbrelimab Q3W via intravenous (IV) infusion, 8mg lenvatinib QD orally, and 1g/m² gemcitabine plus 25 mg/m² cisplatin on Day 1 and Day 8, Q3W by IV for 6 cycles, followed by maintenance aderbrelimab and lenvatinib until disease progression (PD) or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Results: Between April 2024 and November 2025, 26 pathologically-confirmed advanced ICC patients with a median age of 60.5 (range, 45-78) years, including 20 men (76.9%), were enrolled at five centers. At the end of last follow-up (January 20, 2026), the ORR was 46. 2% (12/26; 95% CI: 26.6%-66.6%), and disease control rate (DCR) was 92.3% (24/26; 95% CI:74.9%-99.1%). Median follow-up time was 8.1 months. 12 patients experienced disease progression and 4 patients have died. The median PFS was 8.5 months. The median OS have not been reached. The most common grade 3 or 4 treatment-related adverse events (TRAEs) were neutropenia and thrombocytopenia observed in 6 (23.1%) and 5 (19.2%) patients, respectively. No unacceptable toxicity or treatment-related deaths occurred. Conclusions: Aderbrelimab and lenvatinib in combination with gemcitabine and cisplatin showed promising efficacy with reasonable tolerability in advanced ICC patients. Survival data is immature and will be updated in the future. Clinical trial information: NCT06298968 .