A prospective, observational phase II clinical study evaluating hepatic artery infusion chemotherapy in combination with HLX10 and HLX04 as first-line treatment for patients with advanced hepatocellular carcinoma.

4098 Background: Advanced hepatocellular carcinoma (HCC) presents limited treatment options. Immunotherapy has emerged as an effective treatment, demonstrating encouraging outcomes and acceptable adverse reactions in advanced HCC. This study aims to assess the efficacy and safety of HLX10 (recombinant anti-PD-1 humanized monoclonal antibody) and HLX04 (recombinant anti-VEGF humanized monoclonal antibody), in combination with hepatic artery infusion chemotherapy (HAIC), as first-line treatment for advanced HCC. Methods: This prospective, observational, single-center Phase II trial enrolled untreated HCC patients with BCLC stage C. All patients received HLX10 (4.5 mg/kg, intravenous infusion, every 3 weeks) and HLX04 (15.0 mg/kg, intravenous infusion, every 3 weeks) on Day 1 of each treatment cycle, followed by HAIC with the FOLFOX regimen. HAIC was administered for a maximum of 8 cycles, while HLX10 and HLX04 were continued for up to 2 years, until death, disease progression, or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR), assessed by the investigator according to RECIST v1.1 criteria. Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), and safety. Results: Between August 2023 and September 2024, a total of 35 eligible patients were enrolled in the study. As of the data cut-off, 28 (80.0%) patients had received at least 3 cycles of treatment. Of the 35 patients, 32 underwent at least one assessment of treatment response, with the best outcomes as follows: 17 (53.1%) achieved partial remission (PR), and 12 (40.0%) had stable disease (SD). The ORR and DCR were 53.1% and 90.6%, respectively. Notably, among patients who had received at least 3 cycles of treatment, 17 patients achieved PR, resulting in an ORR of 63.0%. Moreover, 5 patients underwent successful hepatectomy after at least 3 cycles of treatment, and postoperative pathological evaluation revealed extensive tumor necrosis in the excised tissues. The median follow-up duration was 8.4 months, during which 6 (18.8%) patients experienced disease progression, yielding a one-year PFS rate of 70.5% (95% CI: 47.0%–85.0%). In terms of safety, 17 patients (48.6%) experienced at least one grade 3 or 4 adverse event (AE), with the most frequent being decreased lymphocyte count (20%). Conclusions: The combination of HLX10, HLX04, and HAIC as first-line treatment for advanced HCC has demonstrated promising efficacy, particularly in patients completing three or more cycles. The safety profile of this combination therapy was acceptable, with manageable AEs. Further investigation in larger trials is warranted. Clinical trial information: NCT06370065 .