Phase II clinical study of the efficacy and safety of adebrelimab in combination with lenvatinib as second-line treatment for advanced intrahepatic cholangiocarcinoma.

e16215 Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited efficacy of second-line treatment following intolerance or failure of first-line therapy. This study aimed to explore the efficacy, safety, and effectiveness-related biological characteristics of adebrelimab combined with lenvatinib as second-line regimen in patients with advanced ICC. Methods: This single-arm, open-label phase II study enrolled patients with unresectable or metastatic ICC who had experienced progression or intolerance to first-line chemotherapy. Adebrelimab was administered via intravenous infusion (20 mg/kg, Q3W), combined with oral lenvatinib (8 mg for body weight < 60 kg or 12 mg for ≥ 60 kg, once daily). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), time to deterioration(TTD), and disease control rate (DCR), safety and quality of life (QoL). Exploratory endpoints focused on identifying molecular markers in sensitive populations, biomarkers of treatment response, and mechanisms of resistance. Results: As of the data cut-off in January 2025, 10 patients were enrolled, of whom 7 were evaluable. The median age was 53.5 years (IQR, 10.5), and 40.0% had HBV infection history. Most patients (70.0%) were classified as Child-Pugh A and 90.0% met “up to seven” criteria. Two patients (20%) underwent surgery and 80% received transcatheter arterial chemoembolization (TACE) as prior locoregional treatment. Among 7 patients available for imaging evaluation, the ORR was 10.0% (1 partial response (PR), 4 stable disease (SD) , and 2 progressive disease (PD)) and the DCR was 50.0%, based on mRECIST and RECIST 1.1. The most frequently reported treatment-related AEs (any grade) were leukopenia (100.0%), anemia (70.0%), abdominal pain (70.0%), and thrombocytopenia (50.0%). The most common grade 3 or 4 AEs included leukopenia, abdominal pain, thrombocytopenia, vomiting and limb pain, each occurring in 10.0% of patients. Conclusions: Adebrelimab combined with lenvatinib showed promising antitumor activity and manageable safety profile in patients with unresectable or metastatic ICC who had progressed on or were intolerant to first-line chemotherapy. These findings provide a rationale for further investigation of this regimen as a second-line treatment option. Clinical trial information: ChiCTR2300078869 .