Adjuvant Adebrelimab Plus Apatinib for Participants With HCC at High-risk of Recurrence After Curative Resection

Inclusion Criteria:

Participants must meet all of the following conditions in order to be enrolled in this study:

1. Voluntarily participate in this study and sign an informed consent form.

2. Participants diagnosed with HCC through pathological histology/cytology orclinically diagnosed with HCC according to the Diagnosis and Treatment Guidelinesfor Primary Liver Cancer (2024 Edition).

3. Within 4-12 weeks prior to enrollment, radical resection surgery was performed.

4. Complete recovery from surgical resection within 4 weeks prior to enrollment.

5. High risk factors for postoperative recurrence of hepatocellular carcinoma includemultiple tumors, tumor length>5 cm, poor tumor differentiation (Edmondson III-IVgrade), margin ≤ 1 cm, invasion of Microvasculature or large vessels, lymph nodemetastasis, sustained abnormalities in AFP or abnormal prothrombin , etc.

6. Child Pugh liver function rating within 7 days prior to randomization: A or B (≤ 7points).

7. ECOG PS score within 7 days before randomization: 0-1 points.

8. Have not received systematic anti-tumor treatment for hepatocellular carcinoma inthe past.

9. Expected survival time ≥ 12 weeks.

10. The main organ functions meet the following requirements (within 7 days beforerandomization):

(1) Blood routine examination: (excluding hemoglobin, no blood transfusion within 14 days prior to screening, no use of granulocyte colony-stimulating factor [G-CSF], no medication correction):

• Neutrophil absolute count ≥ 1.5 × 109/L; Platelets ≥ 75 × 10^9/L; • Hemoglobin ≥ 90 g/L.(Leukocyte and thrombocytopenia caused by splenic hyperfunction can be included in the group after partial embolization of the splenic artery or medication correction) (2) Blood biochemistry test (no albumin transfusion within 14 days before screening): Serum albumin ≥ 28g/L; Total serum bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; Blood creatinine ≤ 1.5 x ULN or Cr clearance rate>50ml/min (3) International standardized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the range of normal control ≤ 6 (4) Urinary protein<2+(If urinary protein ≥ 2+, 24-hour urine protein quantification is required, and 24-hour urine protein quantification<1.0g can be included in the group).

11. If suffering from hepatitis B virus (HBV) infection, it is necessary to be willingto receive antiviral treatment throughout the study period (according to thediagnostic and treatment guidelines, such as entecavir) and regularly monitor it;Hepatitis C virus (HCV) ribonucleic acid (RNA) positive subjects must receiveantiviral treatment according to the diagnosis and treatment guidelines, and theirliver function must be within CTCAE1 level elevation.

12.Women with fertility: must agree to contraception from the signing of the informed consent form until 90 days after the last use of the study drug (whichever is longer). And the blood HCG test must be negative within 7 days before starting the study treatment; And it must be non lactation period

Exclusion Criteria:

If a subject meets any of the following conditions, they will not be allowed to enter this study:

1. Known hepatobiliary carcinoma, sarcoma like hepatocellular carcinoma, combinedhepatocellular-cholangiocarcinoma，and fibrous layer cell carcinoma; Within 5 yearsor simultaneously suffering from other active malignant tumors other thanhepatocellular carcinoma (excluding cured skin basal cell carcinoma and cervicalcarcinoma in situ).

2. There are uncontrollable extrahepatic metastases, such as lung and brain metastases (EHS).

3. Previously received local treatment, including therapeutic TACE, transarterialembolization (TAE), hepatic artery infusion chemotherapy (HAIC), transarterialradiation embolization (TARE), etc.

4. Participants who are preparing to undergo or have previously received organ orallogeneic bone marrow transplantation.

5. Participants who are currently accompanied by interstitial pneumonia or interstitiallung disease, or have a history of interstitial pneumonia or interstitial lungdisease that requires hormone therapy in the past, or other pulmonary fibrosis,organized pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-relatedpneumonia, idiopathic pneumonia, or subjects with evidence of active pneumonia orsevere lung function impairment seen on chest computed tomography (CT) images duringscreening, are allowed to have radiation induced pneumonia in the radiation field;Active tuberculosis.

6. Currently, there is active autoimmune disease or a history of autoimmune diseasethat may recur (including but not limited to: autoimmune hepatitis, interstitialpneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis,hyperthyroidism, hypothyroidism [subjects that can be controlled only throughhormone replacement therapy can be included]); Subjects with skin diseases that donot need systematic treatment, such as vitiligo, psoriasis, alopecia, controlledtype I diabetes that receive insulin treatment, or childhood asthma that hascompletely alleviated without any intervention after adulthood can be included;Asthma subjects who require medical intervention with bronchodilators cannot beincluded.

7. Suffering from hypertension and unable to achieve good control throughantihypertensive drug treatment (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) (basedon the average BP reading obtained from ≥ 2 measurements), it is allowed to achievethe above parameters through the use of antihypertensive therapy; Previouslyexperienced hypertensive crisis or hypertensive encephalopathy.

8. Participants with moderate to severe ascites with clinical symptoms who requiretherapeutic puncture or drainage, or whose Child Pugh score is greater than 7 (excluding those who only show a small amount of ascites on imaging but do not haveclinical symptoms); Uncontrolled or moderate to equal amounts of pleural effusionand pericardial effusion.

9. There are clinical symptoms or diseases of the heart that cannot be well controlled,such as: (1) According to the standards of the New York Heart Association (NYHA),level II or above cardiac insufficiency or cardiac ultrasound examination: LVEF (left ventricular ejection fraction)<50%; (2) Unstable angina pectoris; (3) Haveexperienced myocardial infarction within one year prior to the start of the researchtreatment; (4) Clinically significant supraventricular or ventricular arrhythmiasrequire treatment or intervention; (5) QTc>480ms (QTc interval is calculated usingthe Fridericia formula; if QTc is abnormal, it can be detected continuously threetimes every 2 minutes, and the average value is taken).

10. History of spontaneous rupture of liver tumors.

11. Individuals with a history of hepatic encephalopathy.

12. Congenital or acquired immune dysfunction in subjects (such as HIV infectedindividuals).

13. There have been incidents of thrombosis or embolism occurring within the first 6months of treatment, such as cerebrovascular accidents (including transient ischemicattacks, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.

14. Participants with a history of gastrointestinal bleeding or a clear tendency towardsgastrointestinal bleeding within 6 months prior to the start of the study treatment,such as those at risk of bleeding or severe esophageal and gastric varices, locallyactive gastrointestinal ulcer lesions, or continuous positive fecal occult blood,cannot be included in the study. (If fecal occult blood is positive during thebaseline period, a follow-up examination is required. If the follow-up examinationis still positive, gastroduodenoscopy (EGD) is required. If EGD indicates a risk ofbleeding, esophageal and gastric varices/other gastrointestinal diseases cannot beincluded in the study.)

15. Within 6 months prior to the start of treatment, there have been abdominal fistulas,gastrointestinal perforation, or abdominal abscesses.

16. Severe, unhealed or cracked wounds, as well as active ulcers or untreated fractures.

17. Known genetic or acquired bleeding (such as coagulation dysfunction) or thrombotictendencies, such as in hemophilia participants; Currently or recently (within 10days prior to the start of research treatment), full dose oral or injectionanticoagulants or thrombolytic drugs (prophylactic use of low-dose aspirin, lowmolecular weight heparin allowed) have been used for therapeutic purposes.

18. Major vascular diseases (such as aortic aneurysm requiring surgical repair or recentperipheral arterial thrombosis) occur within 6 months prior to the start of thestudy treatment.

19. Severe infection within 4 weeks prior to the start of the study treatment, includingbut not limited to hospitalization due to complications of infection, bacteremia, orsevere pneumonia; Oral or intravenous administration of therapeutic antibioticswithin 2 weeks prior to the start of the study treatment (subjects who receiveprophylactic antibiotics, such as preventing urinary tract infections orexacerbation of chronic obstructive pulmonary disease, are eligible to participatein the study).

20. It is known that the active ingredients and excipients contained in theinvestigational drugs (Adebelimumab, Apatinib) in this study have hypersensitivityreactions, or have a history of severe allergies to any other monoclonal antibodiesor anti angiogenic targeted drugs.

21. Use immunosuppressive agents or systemic hormone therapy within 14 days prior to thestart of the study to achieve immunosuppressive effects (dose>10mg/day prednisone orother therapeutic hormones).

22. Received attenuated live vaccine treatment within 28 days prior to the start of thestudy treatment, or expected to receive such vaccines during the treatment periodwith Adebrelimab or within 60 days after the last dose of Adebrelimab.

23. Received other experimental drug treatments within 28 days or 5 half-lives (whichever is longer) prior to the start of the study treatment.

24. According to the judgment of the researchers, the subjects may have other factorsthat may affect the research results or cause the study to be terminated midway,such as alcoholism, drug abuse, other serious illnesses (including mental illness)that require concurrent treatment, serious laboratory test abnormalities, and familyor social factors that may affect the safety of the subjects.