Efficacy and Safety of HAIC in Combination With TQB2868 and Ramucirumab for Second-line Treatment of Advanced Hepatocellular Carcinoma

Inclusion Criteria:

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

• Signed informed consent form;

• The investigator believes that the patient is capable of complying with the studyprotocol;

• Histologically or cytologically confirmed advanced hepatocellular carcinoma (HCC);

• Patients who have received first-line treatment for hepatocellular carcinoma andhave treatment failure or intolerance;

• No prior treatment with HAIC including oxaliplatin;

• Prior treatment with tyrosine kinase inhibitors (TKIs) and/or immunotherapy isallowed;

• At least one measurable, untreated lesion according to RECIST 1.1 criteria;

• Availability of pretreatment tumor tissue sample, if available. If tumor tissue isnot available (e.g., exhausted by previous diagnostic testing), the patient remainseligible for participation in the study;

• ECOG performance status of 0 or 1 within 14 days prior to enrollment;

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

• Adequate hematologic and organ function;

• Any acute clinically significant treatment-related toxicity (from prior therapy)must have resolved to ≤Grade 1 prior to enrollment, except for alopecia;

• Negative HIV antibody test result at screening;

• Patients with active hepatitis B virus (HBV) infection: HBV DNA <2000 IU/mL obtainedwithin 28 days prior to starting study treatment and at least 7 days of antiviraltreatment (according to local standard of care, e.g., entecavir) prior to enrollmentand willingness to continue treatment during the study; Patients with activehepatitis C virus (HCV) infection: HCV RNA <2000 IU/mL obtained within 28 days priorto starting study treatment and at least 7 days of antiviral treatment prior toenrollment and willingness to continue treatment during the study;

• Women of childbearing potential must have a negative pregnancy test (β-HCG) prior toinitiation of treatment, and women of childbearing potential and men (who engage insexual intercourse with women of childbearing potential) must agree to use effectivecontraception continuously during the treatment period and for 6 months after thelast dose of treatment.

Exclusion Criteria:

• Previous treatment with HAIC containing oxaliplatin;

• Expected survival time less than 3 months

• History of meningitis;

• Current or past autoimmune diseases or immunodeficiency;

• Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitisobliterans), drug-induced pneumonia, or idiopathic pneumonia, or evidence of activepneumonia on screening computed tomography (CT) scan. Prior radiation pneumonitis inthe radiation field (fibrosis) is allowed;

• Known active tuberculosis;

• Significant cardiovascular disease within 3 months prior to starting study treatment (e.g., New York Heart Association Class II or greater heart disease, myocardialinfarction, or cerebrovascular accident), unstable arrhythmia, or unstable angina;

• History of congenital long QT syndrome or corrected QT interval >500ms (calculatedusing Fridericia's method) at screening;

• History of uncorrectable electrolyte disturbances such as serum potassium, calcium,or magnesium imbalances;

• Major surgery within 4 weeks prior to starting study treatment (excluding diagnosticprocedures) or anticipation of need for major surgical procedure during the courseof the study;

• History of malignancy other than HCC within 5 years prior to screening, unless therisk of recurrence or death from the previous malignancy is considered negligible (e.g., 5-year overall survival rate >90%) and adequately treated in situ cervicalcancer, non-melanoma skin cancer, localized prostate cancer, in situ ductalcarcinoma, or stage I uterine cancer;

• Severe infection within 4 weeks prior to starting study treatment, including but notlimited to hospitalization for complications of infection, sepsis, or severepneumonia;

• Treatment with therapeutic antibiotics orally or intravenously within 2 weeks priorto starting study treatment. Patients receiving prophylactic antibiotics (e.g., forprevention of urinary tract infection or exacerbation of chronic obstructivepulmonary disease) are eligible for participation in the study;

• Prior allogeneic hematopoietic stem cell transplantation or solid organtransplantation;

• Receipt of attenuated live vaccines within 4 weeks prior to starting study treatmentor anticipated need for such vaccines within 5 months after the last dose of PD-1antibody therapy;

• Untreated or incompletely treated esophageal and/or gastric varices associated withbleeding or patients at high risk of bleeding;

• Concurrent HBV and HCV infection. Patients with a history of HCV infection butnegative HCV RNA PCR results can be considered not infected with HCV;

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

• Inability to comply with follow-up or concurrent participation in another clinicaltrial that may interfere with this study;

• The investigator deems the patient unsuitable for enrollment.