TACE, Sorafenib and PD-1 Monoclonal Antibody in the Treatment of HCC

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death that ranks sixth in terms of incident cases, with an overall 5 years survival of 18%. Despite a significant improvement in treatment strategy, the overall survival of HCC remains low due to high recurrence, progressive liver dysfunction and the high fatality of the disease. Surgical resection has been applied in a number of patients; however, surgery has been associated with a high incidence of recurrence (approximately 70% within 5 years). TACE is generally applied on intermediate-stage HCC. However, TACE is not satisfied with improving overall survival. Therefore, there is an urgent need for effective treatment for these patients. At present, the overall objective response rate (ORR) of single or sequential therapy is not satisfied, and the over survival (OS) improvement is not ideal. Therefore, combined therapy maybe the good choice for patients with advanced HCC. This study focuses on the in-operable, BCLC-B/C HCC patients. Through the combination of local therapy (TACE), anti-angiogenic therapy (Sorafenib), and immunotherapy (PD-1 monoclonal antibody), it is expected to change the tumor microenvironment, restore the immune response, strengthen the anti-tumor effect of various treatments, and improve the therapeutic efficacy in patients with BCLC-B/C HCC.

This study is a single arm, single center, open label study. It is estimated that 60 patients with BCLC-B/C HCC who can not receive radical resection will be enrolled. The trial period of subjects includes screening period, treatment period and follow-up period. The drug treatment was 200 mg of PD-1 monoclonal antibody, intravenous infusion on the first day, every 21 days as a treatment cycle; mesylate sorafenib, 400 mg, oral twice a day, continuous oral; TACE, the lipiodol + blank microspheres and oxaliplatin (100 mg) + epirubicin (50 mg) were injected into the hepatic artery by routine procedure, repeated every 4-6 weeks, and administered for according to the physician in charge, TACE treatment cycles. Treatment continues until the disease progresses, intolerable toxicity occurs, new anti-tumor treatment is started, informed consent is withdrawn, follow-up is lost, death occurs or treatment termination is required。 Screening will be performed between days - 21 and - 4. Informed consent was signed up to 4 weeks prior to the first day of cycle 1 before any screening procedure or evaluation was performed and the trial was fully explained to each subject. Baseline evaluation results must be collected prior to the first trial drug administration (day 1 of cycle 1). Baseline assessments may be performed between days - 3 and - 1 or on day 1 of cycle 1. If performed within 3 days before the first day of cycle 1, the screening results can be used as baseline results. The tumor imaging was evaluated every 4-6 weeks since the first administration, and every 12 weeks (± 7 days) after 24 weeks. If there are clinical indications for disease progression, tumor evaluation is more frequent. In the event of disease progression, unacceptable toxicity, the subject's request to discontinue the trial or the subject's withdrawal of consent, the subject will discontinue the trial treatment. When the trial treatment is stopped, the treatment visit shall be stopped within 7 days after the treatment is stopped in order to stop the treatment examination. After the end of the treatment period (up to 2 years), subjects who can benefit from the study drug will continue to study the treatment of the drug until disease progression, intolerable adverse reactions, withdrawal of intensive care facility (ICF), other anti-tumor treatment, loss of follow-up, death or termination of the study. After the occurrence of a clinical event, if it is judged by the investigators that it should be attributed to the progress of the disease and it is unlikely to recover even if the patient continues to receive treatment, it can be evaluated as clinical deterioration. It is up to the investigator to discuss and decide whether to continue or stop the treatment for the subject and record in the study file. At the end of the study, subjects who are still under study treatment can continue to receive treatment through another extended study or other forms at the discretion of the investigator if they are stable or relieved in the efficacy evaluation and can tolerate the adverse reactions.