| Eligibility |
Inclusion Criteria:
Subjects who meet all of the following criteria are allowed to be enrolled into this study:
1. Volunteer to participate in this clinical study; completely understand and know this
study as well as sign the informed consent form (ICF); be willing to follow and be
able to complete all study procedures.
2. Age = 18 years and = 75 years when ICF is signed.
3. Histopathologically or cytologically confirmed diagnosis of advanced hepatocellular
carcinoma (HCC), Or the clinical diagnosis meets the american association for the
study of liver diseases (AASLD) diagnostic criteria for HCC.
4. prior therapy: Arm A: Never received systemic anti-tumor drug therapy before. Arm B:
Patient has a contraindication or intolerance to, or has failed treatment with 1-line
systemic anti-tumor therapy (PD-1 /L1 -based combination therapies). Arm C: Previously
received second or greater lines of systemic therapy. (Including: 1. PD-1/L1-based
therapy 2. Lenvatinib or Sorafenib).
5. According to the curative effect evaluation criteria in solid tumors (RECIST) v1.1,
assessed by the investigator with at least one measurable lesions. Measurable target
lesions cannot be selected from the site of previous radiotherapy.
(lesions located in the usual radiation area, if confirm progress, can also be
selected as the target lesion).
6. Child-pugh liver function rating within 7 days before the first administration of the
study drug : grade A and good grade B (= 7 points).
7. Arm B,C: The end of previous systematic treatment() must be = 2 weeks before the first
administration of the study drug, and the treatment-related AE should be restored to
the level of NCI -CTCAE = 1 (except hair loss).
8. The patient with HCC has liver surgery or local treatment (hepatic artery
embolization, TACE, hepatic artery infusion, radiofrequency ablation, cryoablation or
percutaneous ethanol injection) , Arm A and B : treatment was received = 4 weeks prior
to the first administration of this study. Arm C: treatment was received = 2 weeks
prior to the first administration of this study; The palliative radiotherapy for bone
metastases was received = 2 weeks prior to the first administration of this study; The
diagnostic liver puncturewas received = 1weeks prior to the first administration of
this study. AEs related to previous local therapy should be recovered to the level of
NCI -CTCAE = 1.
9. The ECOG physical performance score within 7 days before the first administration of
the study drug was 0 or 1.
10. Expected survival = 12 weeks.
11. If HBsAg (+) or HBcAb (+), HBV-DNA must be<2500 copy/ml or = 500 IU/mL or <ULN to be
included in the group, and those with elevated HBV-DNA must agree to receive
nucleoside anti-hepatitis b virus treatment. Subjects with negative HCV antibody (-)
or HCV-RNA were admitted. If HCV-RNA is positive, must agree to receive standard of
anti-virus treatment, and subjects must have ALT and AST = 3×ULN to be enrolled.
Subjects with co-infection of hepatitis b and c should be excluded.
12. The functions of the vital organs meet the following requirements (no blood
transfusion, albumin, colony-stimulating factor, or platelet raising drugs are allowed
within 14 days before the first use of the study drugs); Absolute neutrophil count
(ANC) =1.5×109/L platelet= 100×109/L; Hemoglobin= 90g/ L; Serum albumin= 30g/L; Total
bilirubin= 1.5 ULN, ALT, AST= 5 ULN(exclude the HCV-RNA is positive patients);Serum
creatinine=1.5 ULN or creatinine clearance > 50 mL/min (Cockcroft-Gault formula);APTT,
INR and PT =1.5 ULN; Qualitative analysis of proteinuria=1+; If =2+, 24-hour urine
protein test is required, and the subject must have<1g to be enrolled.
13. For fertile female subjects, the serum pregnancy test must be negative within 7 days
before the first dose.Subject agrees to use effective contraception.
Exclusion Criteria:
Subjects who meet any of the following criteria are not allowed to be enrolled in this
study:
1. Hepatobiliary duct cell carcinoma, mixed cell carcinoma, or fibroblastic layer cell
carcinoma are known.
2. Hepatic encephalopathy within 6 months before the first administration of the study
drug.
3. According to the images, portal vein invasion, inferior vena cava or cardiac
involvement of HCC main portal branch (Vp4) were present. Patients with cancer
thrombus in main portal vein but smooth blood flow in contralateral branch can be
enrolled.
4. Other active malignancies within 3 years prior to the first administration of the
study drug.Curable localized tumors, such as basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, superficial bladder carcinoma, carcinoma in situ
of the prostate, cervical carcinoma in situ, and carcinoma in situ of the breast, can
be included in the group.
5. People who are ready to undergo or have received organ or bone marrow transplants.
6. After appropriate intervention, uncontrollable pleural effusion, pericardial effusion
or ascites still need to be drained frequently (once a month or more frequently).
7. Symptomatic brain or meningeal metastases (unless the patient has been on > treatment
for 3 months, has no evidence of progress on imaging within 4 weeks prior to initial
administration, and tumor-related clinical symptoms are stable).
8. Cerebrovascular accident, Pulmonary embolism, deep vein thrombosis or any other
serious thromboembolism, myocardial infarction, unstable angina pectoris and poorly
controlled arrhythmia occurred within half a year (including QTc interval = 450 ms for
men and = 470 ms for women) (QTc interval was calculated by Fridericia formula).
9. According to the New York heart association (NYHA) standard levels ? or ? cardiac
insufficiency or heart colour to exceed examination: LVEF(left ventricular ejection
fraction) < 50%.
10. Human immunodeficiency virus (HIV) infection.
11. Active tuberculosis.Patients with previous and current cases of interstitial
pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, and severe
impairment of lung function that may interfere with the detection and management of
suspected drug-related lung toxicity.
12. Within 14 days prior to the first administration of the study drug, any active
infection requiring systematic anti-infective treatment occurs.
13. Major surgery was performed within 28 days prior to the first administration of the
study drug. Major surgery in this study was defined as the minimum recovery time of 3
weeks after surgery before the surgery treated in this study could be performed.
14. Within 14 days prior to the first administration of the study drug, participating in
other clinical studies.
15. Subjects requiring systemic treatment with corticosteroids (> 10 mg/ day or equivalent
dose of prednisone) or other immunosuppressants within 14 days prior to or during the
study.In the absence of active autoimmune disease, the inhalation or topical use of
steroids, or adrenal hormone replacement at doses less than 10 mg/ day of prednisone
efficacy, is permitted.
16. Patients who have previously received systemic anti-EGFR monoclonal antibody therapy.
17. History of severe hypersensitivity to any monoclonal antibody or study drug excipient.
18. Pregnant or lactating women.
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