| Eligibility |
Inclusion Criteria:
1. Newly histologically confirmed diagnosis of HCC or strictly consistent with the
clinical diagnostic criteria for HCC according to AASLD guideline;
2. At least one measurable site of disease as defined by modified RECIST (mRECIST)
criteria with spiral CT scan or MRI and has not received local treatment;
3. Technically resectable hepatocellular carcinoma with ipsilateral vein tumor
thrombosis, including Vp1, Vp2, Vp3 portal vein tumor thrombus (PVTT) (Japan JSH
classification) and/or Vv1, Vv2 hepatic vein tumor thrombus (HVTT) (Japan JSH) Type),
but not accompanied with extrahepatic organ metastasis, or main portal
vein,contralateral portal vein, superior mesenteric vein, vena cava tumor
thrombus.Bile duct tumor thrombus can be allowed;
4. tumor burden below 50% of standard liver volume;
5. ECOG PS score: 0~1 points
6. Child-Pugh A or B (<=7);
7. Life expectancy of at least 3 months;
8. Subjects with chronic HBV infection must be on antiviral therapy per regional standard
of care guidelines prior to initiation of study therapy;
9. Adequate blood count, liver-enzymes, and renal function: laboratory test values meet
the following requirements within 7 days prior to enrollment (no blood components,
cell growth factors, albumin and other corrective therapy drugs are allowed within 14
days prior to laboratory test):
1. absolute neutrophil count, ANC=1.5×10^9/L, platelet, PLT=80×10^9/L, hemoglobin,
HGB=8.5 g/dL;
2. total bilirubin, TBIL=1.5×ULN, alanine aminotransferase, ALT and aspartate
transferase, AST=5×ULN, serum Alb=28 g/L;
3. creatinine, Cr = 1.5×ULN or clearance of creatinine, CCr= 50mL/min, Urine
protein<2+;
4. INR= 2 and APTT= 1.5×ULN.
10. Female patients with reproductive potential must have a negative urine or serum
pregnancy test within 7 days prior to start of trial;
11. Patients agreed to join the clinical trial and signed informed consent and are willing
and able to comply with the protocol for the duration of the study including
undergoing treatment, adherence to contraceptive measures, scheduled visits and
examinations including follow up.
Exclusion Criteria:
1. Have received local or systemic treatments in the past, including but not limited to
TACE, immunotherapy, targeted therapy, radiotherapy, radiofrequency therapy, etc.;
2. Diffuse HCC or accompanied by distant metastasis;
3. fibrolamellar carcinoma of liver,cholangiocarcinoma and mixed liver cancer;
4. Insufficient residual liver volume(According to imaging calculations, if there is no
background of cirrhosis, the remaining liver volume is less than 35% of the standard
liver volume; if there is a background of cirrhosis, the remaining liver volume is
less than 40% of the standard liver volume)
5. Active tuberculosis (TB), who are receiving anti-TB treatment or who received anti-TB
treatment within 1 year prior to the first study;Patients with previous or current
objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis,
radiation pneumonia, drug-related pneumonia, and severe impairment of lung function.
6. Patients With II-IV myocardial ischemia and myocardial infarction, poor control of
cardiac arrhythmias; Patients with hypertension who cannot be reduced to the normal
range after antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic
blood pressure > 90 mmHg).
7. A history of gastrointestinal perforations and/or fistulas, intestinal obstruction
(including incomplete intestinal obstruction requiring parenteral nutrition),
inflammatory bowel disease or extensive bowel resection (partial colectomy or
extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative
colitis, or chronic diarrhea within 6 months; Patients with a history of
gastrointestinal bleeding or a clear gastrointestinal bleeding tendency in the past 6
months, such as esophageal varices with bleeding risk, local active ulcer lesions, and
fecal occult blood (++).
8. Severe bleeding tendency or coagulation dysfunction, or receiving thrombolytic
treatment; Any life-threatening bleeding event that has occurred within the previous 6
months, including the need for blood transfusion, surgery or topical treatment, and
continued medication.
9. Autoimmune disease requiring systematic treatment or a history of the disease within 2
years. (such as vitiligo, psoriasis, hair loss or graves' disease).
10. Patients with central nervous system diseases (such as primary brain tumors, stroke,
epilepsy, etc.) or central nervous system metastasis or known brain metastasis.
11. Acute or chronic active hepatitis B or C infection; Human immunodeficiency virus (HIV)
infection (HIV 1/2 antibody positive); . A severe infection that is active or
clinically poorly controlled. Severe infections, including but not limited to
hospitalization for infection, bacteremia, or complications of severe pneumonia,
occurred 1 month before the first study.
12. Contains fibroblastic layer hepatocellular carcinoma, sarcomatoid hepatocellular
carcinoma, bile duct carcinoma and other components; Other malignancies were diagnosed
within 5 years prior to the first administration, excluding radical basal cell
carcinoma of the skin, skin squamous cell carcinoma and/or radical resection of
carcinoma in situ. If other malignancies or liver cancer are diagnosed more than 5
years before administration, a pathological or cytological diagnosis of the relapsed
and metastatic lesions is required.
13. Previous major surgery (craniotomy, thoracotomy, or laparotomy) within 1 month or
unhealed wounds, ulcers, or fractures; Severe arteriovenous fistula; Uncontrolled
metabolic disorders or other non-malignant organ or systemic disease or cancer
secondary reactions and may result in higher medical risk and/or uncertainty in
survival evaluation.
14. Treated with immunosuppressive drugs, live attenuated vaccine, systemic
immunostimulant therapy, or any anti-PD-1, anti-PD-L1/L2 antibody or other
immunotherapy and experimental drugs within 4 weeks or planned during the study
period.
15. Other acute or chronic conditions, psychiatric disorders, or laboratory abnormalities
that may increase the risk of study participation or administration of the study drug,
or interfere with the interpretation of the study results, and classify patients as
ineligible to participate in the study at the discretion of the investigator.
16. Patients with a history of hepatic encephalopathy or a history of liver
transplantation or patients preparing for liver transplantation;
17. Pregnant or lactating women; Known to be allergic to any antibody-targeted drug or
small-molecular-targeted drug ingredient; Or have a history of severe allergic
reactions to other monoclonal antibodies.
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