Camrelizumab, a patinib and radiotherapy in locally advanced, unresectable hepatocellular carcinoma: a phase 2 study

PURPOSE: Given the underexplored combination of immune checkpoint inhibitors, tyrosine kinase inhibitors (TKIs), and radiotherapy in locally advanced, unresectable hepatocellular carcinoma (HCC), this study aimed to evaluate camrelizumab (a PD-1 inhibitor), apatinib (a TKI), and intensity-modulated radiotherapy (IMRT) for this setting and identify potential biomarkers. PARTICIPANTS AND METHODS: This single-arm phase 2 trial enrolled locally advanced, unresectable HCC patients who were systemic treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received IMRT (50-60 Gy) to all lesions plus camrelizumab (200 mg intravenously every 3 weeks) and apatinib (250 mg orally once daily) for up to 2 years. Primary endpoint was progression-free survival (PFS); secondary endpoints included response, overall survival (OS), and safety. RESULTS: Between October, 2020, and November, 2024, 44 patients were enrolled. 40 patients (90.9%) had BCLC stage C disease, including macrovascular invasion in 36 (81.8%) and lymph node spread in 11 (25.0%) cases. Objective response rate was 84.1%. The median PFS was 13.8 months and median OS was not reached. The 24-month PFS rate was 38.1% and OS rate was 70.2%, respectively. Grade 3-4 treatment-related adverse events occurred in 36 patients (81.8%), the most common being thrombocytopenia (36.4%) and hypertension (29.5%). No treatment-related deaths were observed. TP53 mutation in circulating tumor DNA was associated with worse clinical outcomes. CONCLUSION: Camrelizumab and apatinib with radiotherapy demonstrated encouraging efficacy with manageable toxicity in locally advanced, unresectable HCC, warranting randomized trials validation.