Adjuvant Treatment of Patients With High Risk of Recurrent Hepatocellular Carcinoma With Donafenib in Combination With Envafolimab

Inclusion Criteria:

• 18-80 years old, male and female.

• Subjects voluntarily enrolled in this study and signed the informed consent, goodcompliance and co-operated with the follow-up.

• Primary hepatocellular carcinoma with postoperative histopathological diagnosis ofHCC and negative margins.

• Presence of any of the following high-risk factors for recurrence: ① tumor size ≥5.0cm combined with microvascular invasion; ② number of tumors ≥3; ③ presence ofportal vein cancer thrombus (vp1 or vp2 type).

• No recurrence of metastasis confirmed by imaging examination 3-7 weeks aftersurgery.

• ECOG score of 0-1.

• Expected survival ≥ 3 months.

• Child-Pugh score ≤ 7.

• Subjects with no previous antitumour therapy (except antiviral therapy)

• No extra-hepatic metastases or lymph node metastases.

• No significant abnormality in routine laboratory tests (blood test, liver and kidneyfunction, coagulation function, etc.): (1) Criteria for routine blood tests need tobe met (no blood and blood products transfusion within 14 days): a. Absoluteneutrophil value (ANC) ≥ 1.510^9/L; b. Haemoglobin (HGB) ≥ 90g/L; c. Platelet count (PLT) ≥ 7510^9/L. (2) Biochemical tests need to meet the following criteria: a.Serum albumin (ALB) ≥ 35g/L; b. Serum total bilirubin (TBIL) < 1.5Upper Limit ofNormal (ULN); c. Serum glutamic transaminase (AST), alanine aminotransferase (ALT) < 2.5ULN; d. Serum creatinine ≤ 1.5*ULN.

Exclusion Criteria:

• Previous histologically/cytologically confirmed fibroplaque-containinghepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinomaand other components.

• Histologically confirmed positive resection margin (R1 resection), presence of lymphnode metastasis or extrahepatic metastasis.

• Previous or current malignancy other than hepatocellular carcinoma.

• History of hepatic encephalopathy or history of liver transplantation.

• Previous history of allergy to any component of the test drug: Envafolimabmonoclonal antibody, donafini.

• Subjects with poorly controlled persistent postoperative pleural, abdominal orpericardial effusion.

• Previous antitumour therapy (except antiviral therapy).

• History of interstitial lung disease (except radiation pneumonitis not treated withhormones), non-infectious pneumonia.

• Presence of any active autoimmune disease or history of autoimmune disease in thesubject (e.g., the following, but not limited to: autoimmune hepatitis, interstitialpneumonitis, uveitis, enterocolitis, hepatitis, pituitary gland inflammation,vasculitis, nephritis, hyperthyroidism, hypothyroidism subjects with vitiligo orasthma that has been in complete remission in childhood and does not require anyintervention in adulthood may be enrolled subjects with asthma that requires medicalintervention with bronchodilators cannot be included).

• Subjects who are on immunosuppressive, or systemic, or absorbable topical hormonetherapy for immunosuppression (dose >10mg/day prednisone or other equipotenthormone) and continue to use it within 2 weeks prior to enrolment.

• A serious infection (CTCAE > grade 2) such as severe pneumonia, bacteraemia, orinfectious co-morbidities requiring hospitalisation has occurred 4 weeks prior tothe first use of study drug.

• Subjects who have experienced acute cardiovascular disease such as acute cerebralinfarction, acute coronary syndrome, etc. within 1 month, with cardiovascularclinical symptoms or disease not well controlled.

• According to NYHA standard, grade III to IV cardiac insufficiency, or cardiacultrasound examination suggests that the left ventricular ejection fraction (LVEF) <50%

• Uncontrollable hypertension with treated systolic blood pressure > 140 mmHg ordiastolic blood pressure > 90 mmHg, hypertensive crisis or history of hypertensiveencephalopathy

• Patients with a definite tendency to gastrointestinal bleeding, including thefollowing: patients with locally active ulcerative lesions and fecal occult blood {(++) may not be enrolled} those with a history of black stools and vomiting ofblood within 2 months.

• Those with abnormal coagulation function (INR>1.5 APTT>1.5 ULN) and bleedingtendency.

• Prolonged unhealed wounds or fractures major surgical procedures or severe traumaticinjuries, fractures or ulcers within 4 weeks.

• Subjects with congenital or acquired immune deficiency (e.g., HIV-infectedindividuals), or active hepatitis (Hepatitis B reference: HBV DNA test value exceedsthe upper limit of normal Hepatitis C reference: HCV viral titre or RNA test valueexceeds the upper limit of normal).

• Patients with a history of psychotropic substance abuse that cannot be stopped orpatients with mental disorders.

• Patients with concomitant illnesses that, in the investigator's judgement, are aserious hazard to patient safety or interfere with the patient's ability to completethe study.

• Pregnant women, lactating women, and women of childbearing age who are not usingadequate contraception.

• In the judgement of the investigator, Patients who are not suitable for inclusion.