Single-center phase 2 trial of SBRT plus sintilimab and bevacizumab biosimilar in anti-PD-1 refractory hepatocellular carcinoma

Immune checkpoint inhibitor (ICI) resistance in hepatocellular carcinoma (HCC) poses a major therapeutic challenge. The phase 2 ReUNION-1 trial at Tongji Medical College of Huazhong University of Science and Technology (Wuhan, China) evaluated the combination of stereotactic body radiotherapy (SBRT) plus sintilimab (anti-PD-1) and bevacizumab biosimilar (anti-VEGF) to overcome resistance in ICI-refractory HCC. Twenty-one patients with progressive HCC after ICI therapy received SBRT followed by sintilimab 200 mg and bevacizumab biosimilar 15 mg/kg every 3 weeks. The primary outcome, objective response rate in non-irradiated lesions, was 33.3%, with a disease control rate of 66.7%. SBRT achieved 100% local control, with 33.3% of patients experiencing grade 3 or higher adverse events. Median progression-free survival was 6.2 months, and median overall survival was 24.4 months. Responders exhibited lower baseline IFN-γ and elevated IL-6, while post-SBRT increases in IFN-γ, IL-2, and IL-6 correlated with improved outcomes. The authors conclude that the combination of SBRT and sintilimab plus bevacizumab biosimilar was effective and well-tolerated.