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

Abstract

e16162 Background: Advanced intrahepatic cholangiocarcinoma (ICC) carries a dismal prognosis, with limited second-line options after failure of gemcitabine-based chemotherapy. Adebrelimab (anti-PD-L1 antibody) plus lenvatinib has shown potential in hepatobiliary cancers. This study evaluated the efficacy and safety of this combination in advanced ICC patients with heavy tumor burden and impaired liver function. Methods: This single-arm, open-label, phase II study enrolled patients with histologically confirmed unresectable or metastatic ICC who progressed on or were intolerant to first-line chemotherapy. Patients received adebrelimab (20 mg/kg IV Q3W) and oral lenvatinib (8 mg/day for weight < 60 kg; 12 mg/day for ≥60 kg). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety (CTCAE v5.0). Results: As of January 12, 2026, 28 patients were enrolled (median age, 60.0 years). The cohort represented an exceptionally high-risk population: 18 patients (64.3%) had extrahepatic metastases, 13 (46.4%) had vascular invasion, and 20 (71.4%) were Child-Pugh class B. Furthermore, 24 patients (85.7%) met the "up-to-seven" criteria. After a median follow-up of 8.5 months (95% CI, 4.5 to 12.2), the median OS reached 12.2 months (95% CI, 6.3 to not reached), with a 12-month OS rate of 59.5% (95% CI, 40.9% to 86.5%). The median PFS was 6.3 months (95% CI, 4.0 to 12.4). In the ITT population, the ORR was 7.1% (2 of 28) and the DCR was 53.6% (15 of 28); however, response assessment was confounded by early treatment discontinuation or pending evaluations in 12 patients (42.9%). Treatment-related adverse events (TRAEs) of any grade occurred in 27 patients (96.4%). Grade 3-4 TRAEs were reported in 6 patients (21.4%), most commonly hepatic encephalopathy (3 patients, 10.7%), limb/shoulder pain (2 patients, 7.1%), and hyperbilirubinemia (2 patients, 7.1%). No treatment-related deaths were observed. Conclusions: Adebrelimab combined with lenvatinib demonstrated an unprecedented median OS of 12.2 months in second-line advanced ICC. Importantly, this survival benefit was maintained even in a population predominantly comprised of Child-Pugh class B patients with significant tumor burden. This combination represents a potential breakthrough for this difficult-to-treat population and warrants further validation in a randomized controlled trial. Clinical trial information: ChiCTR2300078869.