SHR-1210 Combined With Apatinib Mesylate in the Perioperative Treatment of Hepatocellular Carcinoma

Inclusion Criteria:

1. The patient volunteered to participate in the study and signed an informed consent form
2. ≥18 years of age，Male or female
3. Subjects are diagnosed with histologically or cytologically confirmed HCC
4. Subjects haven't received any systemic treatment for HCC before admission.
5. Subjects enrolled must have measurable lesion(s) according to the RECIST 1.1 standard
6. ECOG performance status of 0 or 1
7. Life expectancy ≥ 12 weeks
8. Subjects are diagnosed with resectable stage IIB, stage IIIA HCC cancer.
9. The main organ's function is normal and it should meet the following criteria(Excludes use of any blood components and cell growth factors during the screening period)

   1. Absolute neutrophil count≥1.5×109 /L
   2. Platelets≥80×109/L ;Hemoglobin≥9.0 g/dL; Serum albumin≥3g/dL
   3. Thyroid stimulating hormone (TSH)≤1.0×upper limit of normal(ULN)（If abnormal, T3 and T4 levels should be examined at the same time）
   4. Total bilirubin (TBIL)≤1.5×upper limit of normal (ULN); ALT and AST≤1.5×upper limit of normal(ULN); AKP≤ 2.5×upper limit of normal(ULN)
   5. Serum creatinine ≤1.5×ULN or creatinine clearance \> 60 mL/minute (using Cockcroft-Gault formula)

Exclusion Criteria:

1. Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma; other active malignant tumor except HCC within 5 years or simultaneously
2. Be ready for or previously received organ or allogenic bone marrow transplantation
3. Moderate-to-severe ascites with clinical symptoms
4. History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage.
5. Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment.
6. Known genetic or acquired hemorrhage or thrombotic tendency.
7. The patient is currently using or has recently used (within 10 days before the start of study treatment) aspirin (\> 325mg / day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol.
8. Thrombosis or thromboembolic event within 6 months prior to the start of study treatment.
9. Cardiac clinical symptom or disease that is not well controlled.
10. Subjects have uncontrollable hypertension (systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg), despite patients have taken the best drug treatment ；Subjects have had a hypertensive crisis or hypertensive encephalopathy
11. Patient develops severe vascular disease within 6 months before the start of study treatment.
12. Patients with severe, unhealed or split wounds and active ulcers or untreated fractures
13. Patients who underwent surgical treatment within 4 weeks prior to the start of study treatment.
14. Factors to affect oral administration (such as patients unable to swallow oral medications, malabsorption syndrome etc. situations evidently affect drug absorption).
15. Patients with gastrointestinal diseases such as intestinal obstruction (including incomplete intestinal obstruction) or those who may have caused gastrointestinal bleeding, perforation or obstruction.
16. There is evidence of intragastric gas that cannot be explained by puncture or recent surgery.
17. Previous or current presence of metastasis to central nervous system.
18. Subjects have history of hepatic encephalopathy.
19. The subject has an interstitial lung disease that is symptomatic or may interfere with the discovery or management of suspected drug-related lung toxicity; previous and current subjects with a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-associated pneumonia, severe impaired lung function, etc.
20. The patient has any active autoimmune disease or a history of autoimmune disease expected relapse.
21. Severe infection within 4 weeks prior to the start of study treatment.
22. A history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease.
23. Prior therapy with any anti-PD-1/PD-L1 drug (specifically targeting T-cell co-stimulation or checkpoint pathways), Sorafenib or Apatinib.
24. Subjects were vaccinated with live attenuated vaccine within 28 days before the first dose or expected to receive this vaccine within 60 days after the last dose or during the study period.
25. Treatment of other investigational product(s) within 28 days prior to the start of study treatment.