Stereotactic body radiotherapy plus cadonilimab and lenvatinib as conversion therapy for potentially resectable hepatocellular carcinoma (UniRTX): A phase II study.

Abstract

e16278 Background: Successful conversion to resectability may improve survival in patients with potentially resectable hepatocellular carcinoma (HCC), while effective conversion strategies remain limited. This study evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with cadonilimab, a PD-1/CTLA-4 bispecific antibody, and lenvatinib as a conversion regimen. Methods: This prospective, single-arm, phase II study enrolled patients with pathologically confirmed HCC considered potentially resectable, defined as macrovascular invasion (portal vein, hepatic veins, or inferior vena cava), or tumor number plus largest diameter > 7 and baseline AFP > 400 μg/L, excluding patients suitable for upfront surgery or with extrahepatic metastasis. Patients received SBRT (18–40 Gy in 3–5 fractions), followed by cadonilimab (10 mg/kg IV Q3W) plus lenvatinib (8 mg PO QD) for 4 cycles. Multidisciplinary assessment determined curative-intent therapy or continuation of systemic treatment. The primary endpoint was objective response rate (ORR) per RECIST v1.1 and mRECIST. Secondary endpoints included conversion rate, pathological complete response (pCR) rate, major pathological response (MPR; ≤30% residual viable tumor) rate, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: From April 18, 2023, to November 14, 2025, enrollment was completed with 30 patients. The median age was 55.5 years, and 73.3% (22/30) had BCLC stage C, with 26 patients undergoing at least one post-baseline radiologic assessment. According to RECIST v1.1, the ORR and DCR were 73.1% (19/26) and 92.3% (24/26), respectively. Based on mRECIST, the complete response (CR) rate, ORR, and DCR were 11.5% (3/26), 80.8% (21/26), and 92.3% (24/26), respectively. Successful conversion was achieved in 18 patients (69.2%, 18/26). Fifteen patients (57.7%, 15/26) proceeded to curative-intent therapy (resection, n = 12; radiofrequency ablation, n = 3), and 3 patients declined surgery. Among resected patients, the pCR and MPR rates were 41.7% (5/12) and 83.3% (10/12), respectively, with R0 achieved in all surgical cases. At the data cutoff of January 5, 2026, the median follow-up was 15.5 months (95% CI, 10.0–27.2). Median PFS was 18.2 months (95% CI, 13.5–NA), and median OS was not reached. All patients experienced treatment-related adverse events (TRAEs) of any grade. Grade ≥3 TRAEs occurred in 26.7% (8/30) of patients, including anaphylaxis, increased ALT/AST, neutropenia, leukopenia, hand–foot syndrome, and gastrointestinal ulcer. No treatment-related deaths or radiation-induced liver disease were observed. Conclusions: SBRT plus cadonilimab and lenvatinib showed encouraging efficacy and manageable toxicity as a conversion strategy for potentially resectable HCC. Clinical trial information: ChiCTR2300068781.