Efficacy and Safety of Intratumoral Injection of Recombinant Human Adenovirus Type 5 Combined With Tislelizumab and Lenvatinib in the Treatment of Advanced Hepatocellular Carcinoma

Inclusion Criteria:

1. Age ≥18 years old, and ≤75 years old, regardless of gender;
2. Primary hepatocellular carcinoma confirmed by histology or imaging;
3. Patients with advanced hepatocellular carcinoma who have not received oncolyticviruses, immutherapy drugs (including anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs), andsystemic therapy (such as anti-VEGF /VEGFR monoclonal antibodies, anti- VEGFR-TKIdrugs, chemotherapy);
4. ECOG performance status 0-1;
5. Child-Pugh score ≤7;
6. There was at least one measurable target lesion according to RECIST 1.1 criteria, andat least one lesion was ≥ 10 mm;
7. The expected survival time was ≥3 months;
8. Laboratory tests during the screening period met the following criteria: i. White blood cell count ≥ 3.0×10^9 /L, absolute neutrophil count ≥1.5×10^9/L,platelet count ≥ 75×10^9/L, hemoglobin > 90g/L ii. INR≤1.5 and APTT≤1.5 times upper limit of normal or partial prothrombin time (PTT) ≤1.5 times upper limit of normal; iii. Total bilirubin ≤2.5 times upper limit of normal; ALT and AST≤5 times upper limitof normal (ULN); Serum creatinine ≤1.5 times the upper limit of normal.
9. They volunteered to participate in this study and signed informed consent.

Exclusion Criteria:

1. Pregnant or lactating women, men or women unwilling to use effective contraception;
2. Diffuse liver cancer or tumor is not suitable for RECIST 1.1 criteria;
3. Patients who have previously received an oncolytic viral agent such as T-VEC;
4. Known allergy to the study drug or its active ingredient, history of allergy to thesame biological agent;
5. HBV DNA quantitation ≥1000 copies.
6. Imaging showed portal vein tumor thrombus more than half of the lumen, inferior venacava tumor thrombus or heart involvement.
7. The patient has had grade ≥2 hepatic encephalopathy within 12 months or currentlyrequires medication to prevent or control hepatic encephalopathy.
8. Confirmed active tuberculosis (TB), known human immunodeficiency virus (HIV) positivepatients, and other serious infections requiring treatment;
9. A history of immunodeficiency or autoimmune disease, or long-term systemic steroidtherapy or any form of immunosuppressive therapy within 7 days before enrollment;
10. A history of other (including unknown primary) malignancies, except for Cured non-melanoma skin malignancies, carcinoma in situ of the cervix, radical stage I uterinecancer, radical ductal carcinoma in situ or lobular carcinoma in situ of the breast (without any systemic treatment), localized prostate cancer that is currentlyconsidered cured after radical surgery, and other solid tumors that have been treatedwith radical surgery for more than 5 years without evidence of recurrence;
11. Known tumors of the central nervous system, including metastatic brain tumors;
12. Accompanied by any unstable systemic disease, including but not limited to: Severeinfections, patients with hypertension whose blood pressure cannot be lowered tonormal after antihypertensive treatment, uncontrolled diabetes mellitus, unstableangina pectoris, cerebrovascular accident or transient ischemic attack, myocardialinfarction (a history of myocardial infarction of 6 months or more is allowed),congestive heart failure, serious arrhythmias requiring medical treatment, renal ormetabolic diseases;
13. With medical contraindications to any contrast-enhanced imaging (CT or MRI);
14. Participants who had participated in an interventional clinical trial within 30 daysbefore screening (Note: Participants who were already in the follow-up phase of theclinical trial could participate in this trial if it was 4 weeks after the last doseof the previous investigational drug).