An Exploratory Clinical Study on Neoadjuvant Treatment of Hepatocellular Carcinoma with QL1706 Combined with Lenvatinib

Inclusion Criteria:

1. Age ≥18 years and ≤ 75 years；

2. Confirmed by pathological or imaging diagnosis as CNLC Ib/IIa/IIb/IIIa HCC (fibroticplate and mixed hepatocellular/cholangiocarcinoma subtypes do not meet the inclusioncriteria);

3. Patients who have not received surgery or systemic treatment before enrollment andhave experienced recurrence within 2 years after surgery can be included;

4. MDT team determines that HCC with high-risk factors for recurrence (such asmacroscopic cancer thrombus, multiple tumors, satellite nodules, tumor diameter > 5cm, imaging vascular invasion or preoperative AFP > 200 U/ml) is resectable;

5. Positive hepatitis B surface antigen, no restrictions on anti-hepatitis B virustreatment;

6. At least one measurable lesion based on the Response Evaluation Criteria in SolidTumors (RECIST 1.1) evaluated by the investigator;

7. Organ function levels must meet the following requirements: i. Adequate bone marrowreserve: absolute neutrophil count >= 1.5 x 10^9/L, white blood cell count >= 3 x 10^9/L, platelet count >= 90 x 10^9/L, and hemoglobin >= 9 g/dL; ii. Liver: plasmaalbumin >= 2.8 g/dL; for patients without liver metastasis, serum bilirubin <= 2xULN, and for patients with liver metastasis, serum bilirubin <= 3xULN; forpatients without liver metastasis, AST and ALT <= 2.5xULN, and for patients withliver metastasis, AST and ALT <= 5xULN; iii. Kidney: serum creatinine <= 1.5xULN;iv. Heart: left ventricular ejection fraction (LVEF) >= 50% (no blood transfusion,no use of hematopoietic growth factors and human albumin within 14 days beforescreening);

8. Non-surgical sterilized female or male subjects of childbearing age, must agree touse a medically approved contraceptive method (such as intrauterine device,contraceptive pills or condoms) for contraception during the study treatment periodand within 6 months after the end of the study treatment period; for non-surgicalsterilized female subjects, the HCG test must be negative within 7 days beforeenrollment and must not be lactating;

9. Child-Pugh: A/B grade (<= 7 points);

10. ECOG performance status 0-1;

11. Expected survival >= 6 months.

Exclusion Criteria:

1. Pregnant or lactating women;

2. Patients with imaging evidence showing portal vein tumor thrombus reaching Vp3 orVp4;

3. Patients who have received PD-1 antibody, PD-L1 antibody, CTLA-4 antibody orlenvatinib before; those who participated in other clinical trials within 30 daysbefore screening;

4. Patients with active tuberculosis infection. Those who have active pulmonarytuberculosis within 1 year before enrollment; those who have had active tuberculosisinfection for more than 1 year before enrollment and have not received regularanti-tuberculosis treatment or tuberculosis is still active;

5. Patients with gastrointestinal malabsorption, gastrointestinal anastomosis or anyother conditions that may affect the absorption of lenvatinib;

6. Patients with NYHA II grade or above congestive heart failure history, unstableangina pectoris, myocardial infarction within 6 months or severe arrhythmia withsignificant cardiovascular damage within 6 months;

7. Within 3 weeks before the first administration of the study drug, patients haveexperienced gastrointestinal bleeding events or active hemoptysis (at least 0.5teaspoons of bright red blood);

8. Patients with bleeding or thrombotic diseases or using X-factor inhibitors oranticoagulants that require monitoring of the international normalized ratio (INR),such as warfarin or similar drugs. Low molecular weight heparin treatment isallowed. Antiplatelet drugs at the treatment dose (such as aspirin ≥ 325 mg/d) arenot allowed to be used during the study process;

9. Patients who require immunosuppressive therapy after organ transplantation; patientswho have received immunosuppressive drugs or systemic corticosteroids to achieveimmunosuppression purposes within 14 days before enrollment (such as > 10 mg/dayprednisone or equivalent drugs);

10. Patients with active ulcers, unhealed wounds or fractures;

11. Patients with hypertension and poor control of blood pressure (systolic bloodpressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg);

12. Patients known to be allergic to any trial drug or excipients;

13. Patients who have had other malignant tumors that have not been cured for more than 5 years, but do not include clearly cured malignant tumors, or curable cancers, suchas basal cell carcinoma or squamous cell carcinoma of the skin, papillary thyroidcarcinoma, localized low-risk prostate cancer, cervical carcinoma in situ or breastcarcinoma in situ, etc.;

14. Patients who have received allogeneic tissue/organ transplantation;

15. Patients with known HIV infection history;

16. According to the investigator's judgment, the subjects have other factors that mayaffect the trial results or cause the study to be forced to stop prematurely, suchas alcohol abuse, drug abuse, other serious diseases (including mental diseases)that require combined treatment, severe laboratory test abnormalities, and factorsaffecting the patient's safety due to family or social factors.