TACE Combined With Sintilimab and Bevacizumab for Unresectable HCC

Inclusion Criteria:

* Intermediate or advanced (Barcelona Clinic Liver Cancer stage B or C) HCC with diagnosis confirmed by histology/cytology or clinically
* Disease not amenable to curative therapies but amenable to TACE
* At least one measurable untreated lesion
* No prior systemic therapy for HCC
* Child-Pugh score class 5-7
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
* Adequate organ and hematologic function
* Life expectancy of at least 3 months
* For women of childbearing potential and for men: agreement to remain abstinent

Exclusion Criteria:

* Diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
* Diffuse HCC
* Portal vein tumor thrombus (PVTT) involves the main trunk and contralateral branch or upper mesenteric vein
* Inferior vena cava tumor thrombus
* Metastatic disease that involves major airways or blood vessels
* Symptomatic, untreated or progressing central nervous system metastasis
* Uncontrolled tumor-related pain
* Patients who received prior systemic therapy, immunotherapy, TACE, transcatheter arterial radioembolization (TARE), transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
* Treatment with systemic immunostimulatory agents
* Use of herbal therapies or traditional Chinese medicines with anti-cancer activity within 2 weeks
* History of malignancy other than HCC within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death
* Uncontrolled ascites, hydrothorax or pericardial effusion
* Prior esophageal and/or gastric varices bleeding within 6 months prior to initiation of study treatment
* Prior life-threatening blood loss or grade 3/4 gastrointestinal bleeding requiring blood infusion, endoscopic or surgical intervention within 3 months
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
* History of gastrointestinal (GI) perforation and/or fistula in the past 6 months
* history of GI obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection, complicated by chronic diarrhea), Crohn's disease, ulcerative colitis or long-term chronic diarrhea
* History of hepatic encephalopathy
* History of organ and stem cell transplantation
* Long-term daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
* Use of immunosuppressive drugs in the past 4 weeks, excluding the routes of topical glucocorticoids or physiological doses of systemic glucocorticoids (ie no more than 10 mg/day of prednisone or equivalent). Temporary use of glucocorticoids for dyspnea symptoms such as asthma and chronic obstructive pulmonary disease is allowed
* History of idiopathic pulmonary fibrosis, interstitial pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
* Active tuberculosis
* Active severe infection; use of antibiotics within 2 weeks prior to injection of sintilimab
* Autoimmune disease or immune deficiency
* Inadequately controlled hypertension; history of hypertensive crisis or hypertensive encephalopathy
* Bleeding diathesis or significant coagulopathy
* Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
* underwent major surgery (craniotomy, thoracotomy or open surgery) within 4 weeks; non-recovery from side effects of these procedure
* History of venous thromboembolism in the past 6 months, but implantable IV ports or catheter-derived thrombosis, superficial venous thrombosis, or thrombosis after conventional anticoagulant therapy are excluded
* Current or recent use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, or cilostazol
* uncontrolled metabolic disorder, non-malignant organ or systemic disease or secondary carcinomatous reaction, with high medical risk and/or uncertainty of life expectancy evaluation
* Other acute or chronic diseases, mental illness, or abnormal laboratory test results that may lead to the following outcomes: increase the risk of participating in study or study drug administration, or interfere with the interpretation of the study results and considered by investigator as "NOT" eligible to participate in this study
* Female patients who are pregnancy or breastfeeding