Cadonilimab combined with lenvatinib and transarterial chemoembolization for non-metastatic unresectable hepatocellular carcinoma: a multicenter, open-label, phase 2 study

Previous research showed promising benefits of transarterial chemoembolization (TACE) plus anti-angiogenic agents and immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (uHCC). This study evaluated the efficacy and safety of cadonilimab combined with lenvatinib and TACE in this population. This was a multicenter, open-label, single-arm, phase 2 study conducted at 8 hospitals in China. Eligible patients had unresectable, non-metastatic hepatocellular carcinoma, with diagnoses confirmed histologically or cytologically, or confirmed clinically in cirrhotic patients according to American Association for the Study of Liver Diseases criteria. Patients received oral lenvatinib (8 mg or 12 mg based on body weight) and intravenous cadonilimab (10 mg/kg every 3 weeks) following the first TACE treatment (maximum of 4). The primary endpoint was progression-free survival (PFS) per RECIST v1.1. From June 2022 to May 2023, a total of 62 patients were enrolled. At data cut-off (June 25, 2025), the median follow-up duration was 25.7 months. According to RECIST v 1.1, the objective response rate (ORR) was 38.3% (95%CI: 26.1%–51.8%), the disease control rate (DCR) was 96.7% (95%CI: 88.5%–99.6%), and median PFS was 11.20 months (95%CI: 8.8–15.6). Median overall survival (OS) was not reached (95%CI: 25.5–NE), with a 24-month OS rate of 68.0% (95%CI: 54.5%–78.3%). The therapeutic efficacy of the triple regimen was observed in both the BCLC stage B and C populations. The most common grade ≥ 3 treatment-related adverse events (TRAEs) were aspartate aminotransferase increased (22.6%), platelet count decreased (21.0%), alanine aminotransferase increased (19.4%), and hypertension (19.4%), all of which were manageable. Cadonilimab plus lenvatinib and TACE showed encouraging antitumor activity in patients with non-metastatic unresectable HCC. The safety profile was tolerable and manageable. The encouraging results observed warrant further study in larger clinical trials for this treatment combination. ClinicalTrials.gov Identifier: NCT05319431; Registration Date: 2022-04-08; https://www.clinicaltrials.gov/ .