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

Abstract

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. 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. 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. Camrelizumab and apatinib with radiotherapy demonstrated encouraging efficacy with manageable toxicity in locally advanced, unresectable HCC, warranting randomized trials validation.