Safety and efficacy of camrelizumab and apatinib in combination with IMRT in unresectable hepatocellular carcinoma: A non-randomised phase 2 study.

e16157 Background: This study aimed to assess the efficacy and safety of combining Camrelizumab (an anti-programmed death 1 antibody) and Apatinib (a tyrosine kinase inhibitor) with intensity-modulated radiotherapy (IMRT) in patients with unresectable hepatocellular carcinoma (HCC). Methods: This non-randomized phase 2 study enrolled patients with unresectable HCC who were either systemic treatment-naïve or refractory/intolerant to first-line targeted therapy. The enrolled patients received IMRT at a dose of 50-60 Gy in 25-30 fractions, with the target volume encompassing all visible lesions. Patients were administered Camrelizumab intravenously at a dose of 200 mg every 3 weeks and Apatinib orally a dose of 250 mg once daily during IMRT, continuing for 2 years or until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), local control (LC) rate, overall survival (OS) and adverse events. Results: From October 2020 to January 2024, 33 patients were included in the preliminary analysis (31 men and 2 women; median age, 57 years range, 39-77 years). Among them, 30 patients were diagnosed with BCLC stage C (90.9%). The median number of lesions was one (range, 1-5), with a median tumor diameter of 6.0 cm (range, 2.6-16.0 cm). Tumor thrombus was observed in 22 cases (66.7%), and lymph node metastases was found in 6 cases (18.2%). The ORR based on RECIST 1.1 and modified RECIST criteria were 78.8% and 90.9%, respectively, with a complete response (CR) rate of 12.1% and 54.5%, respectively. The median follow-up time was 20.0 months (range, 3.3-38.6 months). The LC rate at 2 years was 88.3% (95% CI, 68.1-96.1%). The median PFS was 17.5 months (95% CI, 12.6-NA), and the PFS rate at 2 years was 43.9% (95% CI, 26.1-73.8%). The median OS was 25.9 months (95% CI, 14.0-NA), and OS rate at 2 years was 58.5% (95% CI, 41.9-81.6%). According to CTCAE 5.0, grade 3-4 treatment-related adverse events were observed in 27 patients (81.8%), with the most common being thrombocytopenia (42.5%), leukopenia (33.3%) and hypertension (39.4%). No treatment-related deaths occurred. Conclusions: The combination of systematic therapies involving Camrelizumab and Apatinib with local-regional treatment of IMRT showed promising outcomes and manageable toxicities in patients with unresectable HCC. These findings warrant to be confirmed in phase 3 prospective studies. Clinical trial information: ChiCTR2000035052.