| Eligibility |
Inclusion Criteria:
1. Male or female, age=18 and =75 years old.
2. Subjects with stage IIb, # or IV unresectable / advanced primary hepatocellular
carcinoma, intrahepatic cholangiocarcinoma or mixed hepatocellular cholangiocarcinoma
diagnosed in accordance with the Guidelines for Diagnosis and Treatment of Primary
Liver Cancer of CSCO(2020 Edition).
3. Having = 1 measurable lesion in accordance with the modified Response Evaluation
Criteria in Solid Tumors (mRECIST) (lesions located in the field of previous radiation
therapy cannot be used as target lesions unless there is imaging evidence that the
lesion has progressed or persisted three months after radiation therapy).
4. Have a performance status of 0 or 2 on the ECOG Performance Score, life expectancy =12
weeks.
5. Male and female subjects of childbearing age and their partners must agree to take
effective birth controls (hormone, barrier method or abstinence, etc.) from signing
the ICF to 6 months after the last administration.
6. Subjects should voluntarily participate in this clinical study, are fully aware of the
study, have signed the Informed Consent Forms, and are willing to follow and able to
complete all trial procedures.
Exclusion Criteria:
1. Received systemic anti-tumor therapy within 4 weeks prior to the first administration,
including chemotherapy, immunotherapy, radical radiotherapy, etc.; received palliative
radiotherapy within 2 weeks prior to the first administration; or the adverse events
caused by previous anti-tumor therapy have not recovered to =Grade 1 (except for
alopecia).
2. Have known central nervous system metastases with clinical symptoms.
3. Received any adoptive cellular immunotherapy within 6 months prior to the first
administration.
4. Have undergone major organ surgery (excluding needle biopsy or surgery related to this
indication) within 4 weeks prior to their first administration of the study drug, or
required elective surgery during the study period.
5. Have received or expected to receive glucocorticoids (prednisone >10 mg daily or
equivalents) or other immunosuppressive medications within 14 days prior to the first
administration. Note: For subjects without active autoimmune disorder, inhaled or
topical steroid hormone or equivalent dose of prednisone = 10 mg/day is allowed, and
glucocorticoid is allowed for short-term (= 7 days) preventive treatment (e.g.
contrast media allergy) or for the treatment of non-autoimmune disorder (e.g. delayed
type hypersensitivity to contact allergens).
6. Received live or attenuated vaccine within 4 weeks prior to the first administration
or plan to receive live or attenuated vaccine during the study period.
7. Patients with severe infections that cannot be controlled.
8. Patients with a known history of human immunodeficiency virus (HIV) active infection.
9. Have active autoimmune diseases or have had autoimmune diseases that are likely to
recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel
disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.). Except in the
following cases: type 1 diabetes well controlled with hormone replacement therapy,
hypothyroidism, skin conditions not requiring systemic therapy (such as vitiligo), and
other conditions that are well controlled and that are less likely to relapse as by
the investigator (such as resolved childhood asthma).
10. Organ function during screening should meet the following criteria:
1. Absolute neutrophil count (ANC)<1.5×10^9/L, platelet (PLT)<75×10^9/L, hemoglobin
(Hb)<80g/L, (blood transfusion, platelet and colony stimulating factor therapy
are not allowed within 2 weeks before the test);
2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)>5 times the
upper limit of normal (ULN), and total serum bilirubin>2.5 times the upper limit
of normal (ULN);
3. Creatinine(Cr)>1.5×ULN, and creatinine clearance rate(Ccr) = 60ml/min (estimated
according to Cockcroft-Gault formula). Note: Ccr to be calculated only when Cr
>1.5×ULN;
4. International normalized ratio (INR) = 2.0×ULN, activated partial thrombin time
(APTT) >1.5×ULN.
11. Have a history of serious cardiovascular and cerebrovascular diseases, including but
not limited to:
1. There are serious cardiac rhythm or conduction abnormalities, such as ventricular
arrhythmia, and ?-? degree atrioventricular block, which need clinical
intervention;
2. The mean QT interval corrected by Fridericia method (QTcF) is prolonged
(male>450ms, female>470ms);
3. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or
other grade 3 or above cardiovascular and cerebrovascular events occurring within
6 months before the first administration;
4. Patients with heart failure or left ventricular ejection fraction (LVEF) < 50% in
the New York Heart Association (NYHA) classification =II;
5. Hypertension beyond clinical control;
12. Subjects with previous or current interstitial lung disease, pneumoconiosis, radiation
pneumonia, severe impairment of pulmonary function that may interfere with the
detection and treatment of suspected drug-related pulmonary toxicity. Or uncontrolled
systemic diseases, including diabetes, etc.
13. Had other malignant tumors in the past 3 years, except for any type of carcinoma in
situ that has been cured in the past and cured skin basal cell carcinoma or skin
squamous cell carcinoma.
14. Pregnant women or lactating women.
15. Have a history of drug abuse.
16. Patients with a history of serious dementia, mental status changes or any history of
mental disorder, incapacity or limited capacity.
17. Have participated in other clinical trials and received any unmarketed investigational
drug or treatment within 4 weeks prior to the first administration.
18. Patients who have received anti-tumor treatment with lenvatinib and bevacizumab.
19. According to the judgment of the investigators, other factors that may make the
subjects unsuitable for the study.
|
