| Eligibility |
Inclusion Criteria:
1. Male or non-pregnant female between the ages of 18 and 70;
2. signed informed consent;
3. The researchers believe that patients have the ability to comply with the research
program;
4. hepatocellular carcinoma (HCC) by histological or cytological or clinical diagnosis;
5. imaging examination confirmed extrahepatic dissemination, including at least one
evaluable (according to the criteria of RECIST1.1) extrahepatic metastasis;
6. disease is not suitable for radical surgery;
7. Patients who have not received radiotherapy or treatment with aletirizumab and/or
bevacizumab;
8. Early treatment allows tyrosine kinase inhibitors (TKI) treatment or immunotherapy;
9. Pre-treatment tumor tissue samples (if available); If tumor tissue is available,
submit 1 formalin-fixed, paraffin embedded (FFPE) tumor sample from a paraffin block
(preferred) or approximately 10-15 slides containing unstained, off-the-shelf, serial
sections together with a pathology report within 4 weeks of enrollment. If the FFPE
samples described above are not available, samples of any type (including fine needle
aspiration biopsy samples, cell mass samples [e.g., samples from pleural effusion],
and irrigation samples) may also be accepted. A relevant pathology report shall be
provided with the sample. If tumor tissue is not available (e.g., exhausted for
previous diagnostic tests), the patient remains eligible to participate;
10. ECOG performance status of 0 or 1 within 14 days before enrollment;
11. Child-Pugh A or = 7 grade B within 14 days before enrollment;
12. sufficient hematology and organ function, based on the results of the following
laboratory tests obtained within 14 days before enrollment (unless otherwise
specified): absolute neutropcount (ANC) = 1.5 × 109/L (1500/µL), without granulocyte
colony-stimulating factor support; lymphocyte count = 0.5 × 109/L (500/µL); platelet
count = 75 × 109/L (75, 000/µL) or = 60 × 109/L (60, 000/µL) but normal prothrombin
time without blood transfusion; hemoglobin = 90 g/L (9 g/dL), in order to meet this
criterion, Patients may be allowed to have blood transfusions; AST, ALT and alkaline
phosphatase (ALT) = 5 times the upper limit of the normal value; Serum bilirubin = 3
times the upper limit of the normal value; Serum creatinine = 1.5 times the upper
limit of normal value or calculated creatinine clearance = 50 mL/min (calculated using
Cockcroft-Gault formula); Serum albumin = 28 g/L (2.8 g/dL) Urine cellulose strip test
results in proteinuria < 2 + (performed within 14 days prior to starting study
treatment); patients with baseline cellulose strip test results of = 2 + proteinuria
should collect 24 hours of urine and then must demonstrate < 1g of urine protein in 24
hours.
13. Any acute, clinically significant treatment-related toxicity (caused by previous
treatment) must have been alleviated to = 1 grade before entering the study, except
hair loss;
14. HIV antibody test results were negative at the time of screening;
15. Patients with active hepatitis B virus (HBV) infection: HBV DNA < 2000 IU/mL obtained
within 28 days before the start of study treatment, and at least 7 days of anti-HBV
treatment (according to the local standard treatment, such as entecavir) before the
study and willing to continue treatment during the study
16. Women of childbearing age must have a negative pregnancy test (beta HCG) before
starting treatment, women and men of reproductive age (having sex with women of
reproductive age) must agree to use effective contraceptive measures during treatment
and 6 months after the last dose of treatment.
Exclusion Criteria:
1. History of soft meningitis;
2. Current or previous autoimmune disease or immune deficiency, including but not limited
to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,
rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome,
Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, or multiple
sclerosis, with the following exceptions: patients with autoimmune hypothyroidism and
receiving thyroid hormone replacement therapy were eligible to participate in the
study; patients with controlled type 1 diabetes receiving insulin therapy were
eligible to participate in the study; patients with eczema, psoriasis, chronic lichen
simplex, or vitiligo with dermatologic clinical manifestations only (e.g., patients
with psoriasis arthritis were excluded) were eligible to participate as long as all of
the following conditions were met: 1. Rash area must be < 10% of body surface area; 2.
The disease was well controlled at baseline and required only low-potency topical
glucocorticoids. 3. In the past 12 months, the original condition did not appear to
require psoralen plus A-band ultraviolet radiation, methotrexate, vitamin A acid,
biological agents, oral calcineurin inhibitors or highly active or oral
corticosteroids treatment of acute exacerbation;
3. Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., obliterative bronchitis),
drug pneumonia or idiopathic pneumonia or evidence of active pneumonia on screening
chest computed tomography (CT) scan; A history of radiation pneumonitis in the area of
allowable radiation (fibrosis);
4. known active tuberculosis;
5. Significant cardiovascular disease within 3 months before the start of study treatment
(for example, New York Heart Association grade II or worse heart disease, myocardial
infarction or cerebrovascular accident within 3 months before the start of study
treatment), unstable arrhythmia or unstable angina;
6. History of congenital long QT syndrome or corrected QT interval > 500 ms at screening
(calculated using Fridericia method);
7. history of uncorrectable serum potassium, calcium or magnesium electrolyte disorders;
8. Patients who have undergone major surgery (except diagnosis) within 4 weeks before the
start of study treatment or are expected to undergo major surgery during the study
period;
9. Have had malignant tumors other than HCC within 5 years before screening, except for
those with negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such
as adequately treated in situ cervical cancer, non-melanoma skin cancer, localized
prostate cancer, in situ cancer or stage I uterine cancer;
10. Severe infection within 4 weeks before the start of study treatment, including but not
limited to hospitalization due to infection, bacteremia or severe pneumonia
complications;
11. Oral or intravenous administration of therapeutic antibiotics within 2 weeks prior to
the start of study treatment; Patients receiving preventive antibiotics (e.g.,
prevention of urinary tract infections or chronic obstructive pulmonary disease
exacerbations) were eligible to participate;
12. Previous allogenic stem cell or solid organ transplantation;
13. Patients who have received live attenuated vaccine treatment within 4 weeks before the
start of study treatment, or are expected to receive such vaccine during the treatment
period or 5 months after the last administration of altezumab;
14. Untreated or incompletely treated patients with esophageal and/or gastric varices with
bleeding or high risk of bleeding; Prior to enrollment, patients must undergo
ultrasound, CT, MRI, or liver elasticity testing to assess the size of all varices
(small to large) and be treated according to local standard of care. Patients who have
had a corresponding examination within 6 months prior to starting study treatment do
not need to repeat the examination;
15. Coinfection with HBV and HCV. Patients with a history of HCV infection and a negative
PCR result for HCV RNA were considered not infected with HCV;
16. symptomatic, untreated or progressive central nervous system (CNS) metastases;
Asymptomatic patients with treated CNS disease were eligible for the study if they met
all of the following criteria: they had disease outside the CNS that could be measured
according to RECIST v1.1; they had no history of intracranial hemorrhage or
intraspinal hemorrhage; their metastatic disease was limited to the Cerebellar or
supratentorial region (i.e., they had no midbrain, pontine, medullary, or spinal cord
metastases); there was no evidence of progression between completing CNS-guided
therapy and starting study treatment; the patients had not been treated with
stereotactic, whole brain radiotherapy, and/or neurosurgical resection within 28 days
prior to starting study treatment; and the patients did not have the need for ongoing
glucocorticoid therapy for CNS disease. A stable dose of anticonvulsant therapy was
allowed. Asymptomatic patients with newly detected CNS metastases at screening, after
radiotherapy or surgery, were eligible to participate in the study without the need
for repeat screening brain scans;
17. patients can not accept follow-up or are participating in other liver cancer
comprehensive treatment of the relevant clinical trials;
18. The researchers believe that subjects who are not suitable for the study.
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