HAIC Combined With TQB2450 and Anlotinib in Second-line Treatment of Advanced Hepatocellular Carcinoma

Inclusion Criteria:

• Male or non-pregnant female aged 18-80 years or older;

• Diagnosed as advanced hepatocellular carcinoma (HCC) by histology, cytology, orclinical examination;

• Signed informed consent form

• The patient has received first-line treatment for hepatocellular carcinoma and thetreatment has failed or is intolerable;

• Previously received HAIC treatment containing platinum;

• Early treatment allows for receiving tyrosine kinase inhibitor (TKI) treatment orbevacizumab treatment;

• Allow to receive immunotherapy in the early stage;

• At least one measurable lesion (according to RECIST 1.1 standard);

• Tumor tissue samples before treatment (if available)；

• Child Pugh A grade or ≤ 7 B grade within 14 days prior to enrollment;

• HIV antibody test result was negative during screening

• HIV antibody test result was negative during screening

• Any acute, clinically significant treatment-related toxicity (caused by previoustreatment) must have been alleviated to ≤ 1 level before enrollment in the study,except for hair loss

• Patients with active hepatitis B virus (HBV) infection: HBV DNA<2000IU/mL obtainedwithin 28 days before starting the study treatment, and received at least 7 days ofanti HBV treatment (according to local standard treatment, such as entecavir) beforejoining the study, and were willing to continue to receive treatment during thestudy period; Patients with active hepatitis C virus (HCV) infection:HCVRNA<2000IU/mL obtained within 28 days prior to the start of study treatment, andwho have received at least 7 days of anti HCV treatment before enrollment in thestudy and are willing to continue treatment during the study period

Exclusion Criteria:

• Previously received treatment with mitoxantrone;

• History of soft meningitis;

• Current or past autoimmune diseases or immunodeficiencies;

• Idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitisobliterans), drug-induced pneumonia or idiopathic pneumonia, or evidence of activepneumonia can be seen on screening chest computed tomography (CT) images. Allowradiation zone (fibrosis) to have radiation induced pneumonia;

• Known active tuberculosis;

• Within 3 months prior to the start of the study treatment, there was a significantcardiovascular disease, unstable arrhythmia, or unstable angina;

• History of congenital long QT syndrome or corrected QT interval duringscreening>500ms ;

• History of electrolyte disorders such as uncorrectable serum potassium, calcium, ormagnesium;

• Received major surgical treatment within 4 weeks prior to the start of the study (excluding diagnosis) or expected to undergo major surgical treatment during thestudy period;

• Previously diagnosed with malignant tumors other than HCC within the 5 years priorto screening, excluding those with negligible risk of metastasis or death (e.g. 5-year OS rate>90%), such as fully treated in situ cervical cancer, non melanomaskin cancer, localized prostate cancer, in situ or stage I uterine cancer;

• Within 4 weeks prior to the start of the study treatment, there was a severeinfection, including but not limited to hospitalization due to complications such asinfection, bacteremia, or severe pneumonia;

• Administer therapeutic antibiotics orally or intravenously within 2 weeks prior tostarting the study treatment. Patients who receive prophylactic antibiotics (such aspreventing urinary tract infections or exacerbation of chronic obstructive pulmonarydisease) are eligible to participate in the study;

• Previous allogeneic stem cell or solid organ transplantation;

• Received attenuated live vaccine treatment within 4 weeks prior to the start of thestudy, or expected to receive such vaccine during PD-1 monoclonal antibody treatmentor within 5 months after the last dose of PD-1 monoclonal antibody;

• Untreated or incompletely treated esophageal and/or gastric varicose patients withaccompanying bleeding or high risk of bleeding;

• Simultaneously infected with HBV and HCV;

• Symptomatic, untreated, or gradually progressing central nervous system (CNS)metastases.