Sintilimab+Bevacizumab+TACE vs. Lenvatinib+TACE for Advanced HCC

Inclusion Criteria:

• Advanced HCC (BCLC stage C) with diagnosis confirmed pathologically or clinically
• Disease amenable to TACE
• No prior systemic therapy, TACE, transcatheter arterial radioembolization (TARE),transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
• Child-Pugh class A
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
• Life expectancy of at least 3 months
• At least one measurable intrahepatic lesion
• Adequate organ and hematologic function
• Patients with active hepatitis B are allowed, but they need to receive antiviraltreatment to achieve a HBV DNA<10^2 IU/mL
• Patients with hepatitis C need to finish the anti-HCV treatment

Exclusion Criteria:

• Tumor thrombus involving main portal vein or both the first left and right branch ofportal vein
• Vena cava invasion
• Central nervous system metastasis
• History of hepatic encephalopathy
• History of organ and cell transplantation
• Uncontrolled ascites, hydrothorax or pericardial effusion
• Prior esophageal and/or gastric varices bleeding within 6 months prior to initiationof study treatment
• Presence of known severe (G3) varicose veins in endoscopy within 3 months before thefirst dose. Evidence of portal hypertension (including the finding of splenomegaly inimaging studies) with a high risk of bleeding assessed by the investigator
• Presence of any life-threatening bleeding events within the past 3 months, includingthe need for transfusion, surgery or local treatment, and continuous medicationtherapy
• Any arterial or venous thromboembolic events within 6 months, including myocardialinfarction, unstable angina, cerebrovascular accident or transient cerebral ischemicattack, pulmonary embolism, deep vein thrombosis, or any other history of seriousthromboembolism. Presence of implantable venous port or catheter-derived thrombosis,or superficial venous thrombosis, barring stable thrombosis following the conventionalanticoagulation treatment. Prophylactic use of low-dose low-molecular-weight heparin (e.g., enoxaparin 40 mg/day) is permitted.
• A 10-day consecutive dosing of aspirin (> 325 mg/day) or other drugs, e.g.,dipyridamole and clopidogrel, known to inhibit the platelet function within 2 weeksbefore the first dose
• Uncontrolled hypertension after the optimal medical treatment, history of hypertensivecrisis or hypertensive encephalopathy.
• Symptomatic congestive cardiac failure (NYHA Class II-IV). Symptomatic or poorlycontrolled arrhythmia. History of congenital long QT syndrome or corrected QTc > 500ms (calculated using Fridericia formula) during screening
• Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytictherapy
• History of gastrointestinal perforation and/or fistula, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensivebowel resection (partial colectomy or extensive small bowel resection accompanied withchronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within thepast 6 months
• History or current experience of pulmonary fibrosis and such lung diseases asinterstitial pneumonia, pneumoconiosis, drug-related pneumonia, and severely impairedlung function
• Active tuberculosis (TB), currently receiving anti-tuberculosis treatment or receivedsuch treatment within 1 year before the first dose
• Human immunodeficiency virus (HIV) infected (HIV 1/2 antibody positive) and knownsyphilis infection requiring treatment
• Active or poorly clinically controlled serious infections. Severe infections within 4weeks before the first dose, including but not limited to hospitalization caused byinfection, bacteremia, or severe pneumonia complication
• Presence of active autoimmune diseases requiring systemic treatment (e.g., use ofdisease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years beforethe first dose. Use of alternative therapies (e.g., thyroxine, insulin, orphysiological corticosteroids for adrenal or pituitary insufficiency) is permitted.Known history of primary immunodeficiency diseases. For patients with positiveautoimmune antibodies only, they should be assessed by the investigator to determinewhether they had an autoimmune disease
• Receipt of immunosuppressants within 4 weeks before the first dose, excluding localglucocorticoids administered by nasal, inhaled, or other topical routes, or systemicglucocorticoids of physiological doses (no more than 10 mg/day of prednisone orequivalents), while the temporary use of glucocorticoids for preventing allergies ortreating dyspneic symptoms of such diseases as asthma and chronic obstructivepulmonary disease is permitted
• Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeksbefore the first dose or having unhealed wounds, ulcers, or fractures. Receipt oftissue biopsy or other minor surgeries within 7 days before the first dose, barringvenipuncture and catheterization for intravenous infusion.
• Receipt of systemic treatment with traditional Chinese medicines with cancerindications or immunomodulators (including thymosin, interferon, and interleukin,barring local use for controlling pleural fluid or ascites) within 2 weeks before thefirst dose
• History of malignancy other than HCC
• Known hypersensitivity to any ingredients in sintilimab, bevacizumab and lenvatinibpreparations or previous severe hypersensitivity reactions to other monoclonalantibodies
• Pregnant or breastfeeding female patients
• Acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that maylead to the following consequences: increased study participation or drug-relatedrisks, or interference with interpreting trial results, and considered ineligible forparticipating in the trial by the investigator