Camrelizumab Combined With Apatinib for Perioperative Treatment of Resectable Primary Hepatocellular Carcinoma

Inclusion Criteria:

• Patients volunteered to participate in this study and signed informed consent;

• Age 18-75, male or female;

• ECOG PS score 0-1;

• Child-pugh liver function grading: Grade A

• The clinical diagnosis conforms to primary hepatocellular carcinoma (HCC) and thelesion conforms to the indications for resectable operation in the Guidelines fordiagnosis and Treatment of HCC (2019) edition;

• According to the preoperative evaluation of the researcher, the patient had a highrisk of recurrence and met at least one of the risk factors:

Ⅰb: a single tumor diameter > 6.5 cm (except Mr Tian Bangxiong inflating) There were 2-3 tumors with the maximum diameter ≤3cm;Ⅱa : tumor 2-3, biggest > 3 cm indiameter；Ⅱb: tumor 4 or higher；Ⅲa : there are visible to the naked eye vascularinvasion;

• According to RECIST 1.1 standard, patients have at least one measurable lesion (CT/MRI scan long diameter ≥10mm or CT/MRI scan short diameter ≥15mm for lymph nodelesions, and the lesion has not received radiotherapy, freezing or other localtreatments);

• Expected survival ≥ 6 months;

• The function of vital organs meets the following requirements (excluding the use ofany blood component and cell growth factor within 14 days) :

Blood routine:

Neutrophils ≥1.5×109/L Platelet count ≥100×109/L Hemoglobin ≥90g/L;

Liver and kidney function:

Serum creatinine (SCr) ≤ 1.5 times upper limit of normal value (ULN) or creatinine clearance ≥50 ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); AST or ALT levels ≤ 2.5 times the upper limit of normal value (ULN);Urine protein <2+;If urinary protein ≥2+, 24-hour quantitative urine protein must be ≤1g;

• Normal coagulation function, no active bleeding and thrombotic disease A.International standardized ratio INR≤1.5×ULN; B. Partial thromboplastin timeAPTT≤1.5×ULN; C. Prothrombin time PT≤1.5ULN;

• Women of childbearing age should agree to use contraceptives (such as intrauterinedevices, contraceptives or condoms) during and within six months of the end ofmedication;Patients with negative serum or urine pregnancy tests within 7 days priorto study inclusion and who must be non-lactating, and males should agree to usecontraceptives during the study period and for 6 months after the end of the studyperiod;

• Subjects have good compliance and cooperate with the follow-up.

Exclusion criteria:

• Have received radiotherapy, chemotherapy, concurrent chemoradiotherapy or othertargeted therapies before;

• Known hepatobiliary cell carcinoma, sarcomatoid hepatocellular carcinoma, mixed cellcarcinoma and fibre-lamellar cell carcinoma;Active malignancies other than HCCwithin 5 years or concurrently;

• Having hypertension that cannot be well controlled by antihypertensive drug therapy (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);Previoushistory of hypertension crisis or hypertensive encephalopathy;

• Subject has previous or concurrent malignancies (except cured basal cell carcinomaof skin and carcinoma in situ of the cervix);

• Previous treatment with Karillizumab or other PD-1/PD-L1 treatment could not beenrolled;Subjects are known to have prior allergies to macromolecular proteinpreparations or to any carrylzumab or apatinib excipients;

• Subject has any active autoimmune disease or history of autoimmune disease (such as,but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis,enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis,hyperthyroidism, hypothyroidism;Subjects with vitiligo or childhood asthma have beencompletely relieved and may be included as adults without any intervention;Asthmarequiring medical intervention with bronchodilators will not be included);

• Subjects are receiving immunosuppressive, or systemic, or absorbable local hormonetherapy for immunosuppression purposes (>10mg/ day prednisone or other therapeutichormones) and continue to receive such therapy within 2 weeks prior to enrollment;

• Ascites or pleural effusion with clinical symptoms require therapeutic puncture ordrainage;

• Clinical symptoms or diseases of the heart that are not well controlled, such as:

1. NYHA2 or above heart failure

2. Unstable angina pectoris

3. Myocardial infarction occurred within 1 year

4. Patients with clinically significant supraventricular or ventricular arrhythmiarequiring treatment or intervention;

• The patient currently (within 3 months) has gastrointestinal diseases such asesophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portalhypertension, or active bleeding in unresected tumors, or other conditionsdetermined by the researchers that may cause gastrointestinal bleeding orperforation;

• Past or present severe bleeding (>30 ml bleeding within 3 months), hemoptysis (>5 mlfresh blood within 4 weeks) or thromboembolic events (including stroke events and/ortia) within 12 months;

• Subject has active infection or unexplained fever of >38.5 degrees during screeningand before first administration (subject's fever due to tumor can be enrolledaccording to the investigator's judgment);

• Patients with past or present objective evidence of pulmonary fibrosis, interstitialpneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severeimpairment of lung function, etc.;

• Subjects with congenital or acquired immune deficiency, such as HIV infection, oractive hepatitis (transaminase does not meet the inclusion criteria, hepatitis Breference: HBV DNA≥1000/ml;Hepatitis C reference: HCV RNA≥103/ml);Chronic hepatitisB virus carriers, HBV DNA < 1000 IU/ml, must receive antiviral treatment at the sametime during the test can be enrolled;

• Live vaccine is administered less than 4 weeks before or possibly during the studyperiod;

• The subject has a known history of psychotropic substance abuse, alcohol abuse ordrug abuse;

• The subject cannot or does not agree to bear the cost of the self-funded portion ofthe examination and treatment, except for the clinical study drug, combinedchemotherapy and SAE related to the clinical study drug combined chemotherapy;

• Researchers think that should be left out in this study, the researchers determine,for example, the subjects have other factors that may result in this study wereforced to midway termination, such as, other serious disease (including mentalillness) need to merge treatment, there are serious abnormal laboratory examination,accompanied by factors such as family or society, will affect the safety of thesubjects, or information and the collection of the sample.