| Eligibility |
Inclusion Criteria:
1. Signed written informed consent before screening;
2. Age = 18 years old =75 years old for both men and women;
3. ECOG score 0-1;
4. A clinical or pathological diagnosis of hepatocellular carcinoma should meet one of
the following criteria: ? A histological or cytological diagnosis of hepatocellular
carcinoma, except for fibrolamellar, sarcomatoid or mixed cholangiocarcinoma; ?
According to the Diagnosis and Treatment Guidelines for Primary Liver Cancer (2022
Edition), the patient was clinically diagnosed with HCC;
5. Hepatitis B virus surface antigen (HBsAg) positive and hepatitis B virus (HBV)
DNA<2000IU/ml or 104 copies /ml; Or hepatitis B virus core antibody (HBcAb) positive,
HBsAg negative, and highly sensitive HBV DNA<2000IU/ml or 104 copies /ml;
6. have not previously received any systemic therapy for HCC (mainly including systemic
chemotherapy, antivascular therapy, molecular targeted therapy, immunotherapy
targeting any other antibodies or drugs that act on T-cell co-stimulation or immune
checkpoint pathways, Including but not limited to anti-PD-1, anti-PD-L1 /L2,
anti-CD137 or anti-ctLA-4 antibodies), and disease progression 6 months after the end
of postoperative adjuvant chemotherapy were allowed to be enrolled;
7. Chinese clinical stage of liver cancer (CNLC) ?b or CNLC ?b-?a which is not suitable
for surgery and/or local treatment;
8. Child-Pugh rating for liver function: Grade A and good Grade B (=7 points), and no
history of hepatic encephalopathy;
9. There is at least one measurable lesion according to the efficacy evaluation criteria
for solid tumors (RECIST version 1.1), and there is definite disease progression for
lesions previously treated locally
Can be selected as a target lesion;
10) Expected survival of more than 3 months;
11) Major organ function is normal (no blood component, cell growth factor or albumin
infusion therapy has been given within 14 days prior to laboratory examination), if the
following criteria are met:
1. Blood routine: neutrophil =1.5×l09/L, platelet =75×109/L, hemoglobin =90g/L;
2. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
ALT and AST=5×ULN; Serum albumin =28g/L; Total bilirubin (TBIL) =2×ULN; Alkaline
phosphatase (ALP) =5×ULN;
3. Renal function: serum creatinine (Cr) =1.5×ULN or creatinine clearance (Ccr)
=50mL/min;
4. Urine protein <2+ by routine detection; If urine protein =2+ at baseline, 24-hour
urine protein quantity must be =1.0g;
5. Coagulation function: activated partial thromboplastin time (APTT), International
Normalized Ratio (INR), prothrombin time (PT) =1.5×ULN;
6. Echocardiography: left ventricular ejection fraction (LVEF) =50%;
Exclusion Criteria:
1. Liver surgery and/or local treatment for HCC, except palliative radiotherapy for
bone metastases to relieve pain, had been performed within 4 weeks prior to
initial study drug therapy;
2. Subjects (except hair loss and fatigue) who have not recovered from any toxicity
and/or complications of local therapy (including interventional therapy, radio
frequency therapy, etc.), previous chemotherapy, surgery, radiotherapy, that is,
have not fallen to = Grade 1 (NCI CTCAE version 5.0);
3. Have received anti-tumor drug therapy in the past (including but not limited to
traditional Chinese medicine preparations with anti-tumor indications);
4. With moderate or severe ascites or ascites requiring drainage, or with pleural or
pericardial effusion requiring drainage and/or symptoms of shortness of breath;
5. with known active central nervous system metastases (CNS) and/or cancerous
meningitis;
6. With other malignancies (other than cured cervical carcinoma in situ,
non-melanoma skin cancer or other tumors/cancers that have been treated radically
and have shown no signs of disease for at least 5 years);
(7) Combined history of bleeding tendency, high risk of bleeding, or cocoagulation
dysfunction, including an arteriovenous thromboembolism event, including myocardial
infarction, unstable angina, cerebrovascular accident, or transient ischemic attack,
pulmonary embolism, deep vein thrombosis, or any other severe thromboembolism in the 6
months prior to screening;
8) The portal vein cancer thrombus involved the main trunk, or both the main trunk and
the superior mesenteric vein, or the inferior vena cava cancer thrombus or heart
involvement;
9) Unhealed wounds, active digestive tract ulcers or bleeding, fractures (excluding
healed old fractures);
10) Esophageal or gastric varicose bleeding occurred within 6 months prior to
treatment, or severe varicose veins were known to exist on endoscopic examination.
11) A history of gastrointestinal perforation and/or fistula, abdominal abscess,
intestinal obstruction (including incomplete intestinal obstruction requiring
parenteral nutrition), extensive enterectomy (partial resection of the colon or
extensive resection of the small intestine with chronic diarrhea), Crohn's disease,
ulcerative colitis, or long-term chronic diarrhea within 6 months prior to treatment;
12) Patients who had undergone major surgery within 4 weeks prior to enrollment or
expected to undergo major surgery during the study period (except for diagnostic
biopsy);
13) Having a known or suspected autoimmune disease (e.g., systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid
disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), having a history
of human immunodeficiency virus infection (HIV positive), or having other acquired or
congenital immunodeficiency diseases.
14) Patients with a history of active tuberculosis or active or uncontrolled infection
requiring systematic treatment (except simple urinary tract infection or upper
respiratory tract infection) or syphilis infection requiring treatment;
15) Subjects with a combined history of interstitial lung disease, non-infectious
pneumonia, or high suspicion of having interstitial lung disease; Subjects with a
history of drug-induced or radiological noninfectious pneumonia without symptoms were
admitted;
16) A history of severe medical disease, such as grade III or higher cardiac
dysfunction (New York Heart Association [NYHA]), ischemic heart disease (such as
myocardial infarction or angina), or myocardial infarction within the 3 months prior
to enrollment, Subjects with poorly controlled diabetes (fasting blood glucose
=10mmol/L) after medication or hypertension (systolic blood pressure >140mmHg and/or
diastolic blood pressure >90mmHg) after medication and with prior hypertensive crisis
or hypertensive encephalopathy;
17) Receive live vaccines (except seasonal influenza vaccines that do not contain live
viruses) within 4 weeks before the first study drug treatment or during the planned
study period;
18) Allergic to any component of tirelizumab or Lenvatinib, or known allergic to any
other monoclonal antibody;
19) Pregnant or lactating women, or subjects who plan to become pregnant during the
treatment period and within 6 months after the end of treatment; Unwillingness to use
effective contraception (including male subjects with the ability to impregnate women
and female subjects and their male partners) during the study and for at least 6
months after the last study medication;
20) The subject is known to have a history of drug addiction or mental illness;
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