hepatocellular carcinoma
Conditions
Interventions
treatment group:JS004 in combination with Toripalimab and Bevacizumab
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-75 years, no restriction on gender. 2. Histologically/cytologically confirmed hepatocellular carcinoma (HCC), or meeting the clinical diagnostic criteria for HCC according to the American Association for the Study of Liver Diseases (AASLD) in cases of cirrhosis. 3. HCC classified as stage B (intermediate) or C (advanced) according to the Barcelona Clinic Liver Cancer (BCLC) staging system, not suitable for surgery and/or local therapy, or disease progression after surgery and/or local therapy. 4. No prior systemic therapy for HCC (including systemic chemotherapy, anti-angiogenic agents, other molecular targeted therapies, or immunotherapy involving CTLA-4, PD-1/PD-L1 monoclonal antibodies). 5. At least one measurable lesion according to RECIST v1.1 criteria. 6. Child-Pugh liver function classification of grade A or grade B = 12 weeks. 9. Major organ function meeting the following requirements: no blood transfusion, hematopoietic stimulants (including G-CSF, GM-CSF, EPO, TPO), or human albumin preparations within 14 days prior to screening. - Absolute neutrophil count >= 1.5×10^9/L - Platelet count >= 75×10^9/L - Hemoglobin >= 90 g/L - Serum albumin >=29 g/L - Total serum bilirubin = 40 mL/min (calculated using the Cockcroft-Gault formula) - International normalized ratio (INR) <= 2 or prothrombin time (PT) exceeding the ULN by <= 6 seconds - Urine protein < 2+ (if urine protein = 2+, a 24-hour urine protein quantification should be performed, and subjects with 24-hour urine protein < 1.0g can be enrolled). 10. For subjects with HBsAg(+) and/or HBcAb(+), HBV DNA must be < 1000 IU/mL (if the local center's lower limit of detection exceeds 1000 IU/mL, eligibility will be determined after discussion with the investigator), and subjects must continue ongoing antiviral therapy for HBV or initiate full treatment with entecavir or tenofovir during the study. 11. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment and agree to use effective contraception during the study and for 60 days after the last dose of study drug. Male subjects with female partners of childbearing potential must also agree to use effective contraception during the study and for 60 days after the last dose of study drug. 12. Subjects must voluntarily participate, provide informed consent, sign a written informed consent form, and have good compliance.
Exclusion criteria
Exclusion criteria: 1. Known intrahepatic cholangiocarcinoma (ICC), mixed type liver cancer, sarcomatoid liver cancer, or fibrolamellar hepatocellular carcinoma. 2. A history of other malignant tumors (excluding HCC) within the past 5 years; however, definitively treated localized tumors, such as carcinoma in situ of the cervix, basal cell carcinoma of the skin, and prostate carcinoma in situ, are excluded. 3. Underwent liver surgery and/or local therapy for HCC or received experimental drugs within 4 weeks prior to enrollment; received palliative radiotherapy for bone metastases within 2 weeks before enrollment; used herbal medicine with anti-HCC effects within 2 weeks before enrollment. Unresolved toxicities from previous treatments (except for hair loss) not recovered to =Grade 3 (according to NCI-CTCAE v5.0) gastrointestinal or non-gastrointestinal fistulas. 8. Tumor invasion of the main trunk of the portal vein (Vp4) exceeding 50% of the lumen, tumor thrombus in the inferior vena cava, or cardiac involvement based on CT/MRI. 9. History of severe cardiovascular or cerebrovascular disease: a) Congestive heart failure of NYHA class II or higher, unstable angina, myocardial infarction, stroke, or uncontrolled arrhythmias within 12 months before enrollment. b) LVEF (left ventricular ejection fraction) 480ms (calculated using Fridericia's formula; if QTc is abnormal, three consecutive tests 2 minutes apart should be performed, and the average value taken). c) Uncontrolled hypertension (systolic BP >=150 mmHg and/or diastolic BP >=100 mmHg based on the average of at least 3 readings obtained from >=2 measurements). History of hypertensive crisis or hypertensive encephalopathy. 10. Other significant bleeding tendencies or evidence of major coagulation disorders: any clinically significant hemoptysis or tumor bleeding within 2 weeks prior to enrollment; thrombosis or embolic events within 6 months before enrollment; anticoagulation therapy (except for low molecular weight heparin) within 2 weeks before enrollment; or requiring antiplatelet therapy. 11. Major surgery within 4 weeks before enrollment, excluding diagnostic biopsies. 12. Existing central nervous system metastasis; if suspected, MRI of the brain and/or spine should be performed to exclude. 13. Severe unhealed wounds, active ulcers, or untreated fractures. 14. Receipt of live vaccines within 30 days prior to enrollment. 15. Immunodeficiency or current long-term systemic steroid therapy (daily dose >10 mg prednisone or equivalent corticosteroids) or other immunosuppressive treatments within 7 days prior to enrollment. 16. Active autoimmune diseases requiring systemic treatment (e.g., immunomodulatory drugs, corticosteroids, or immunosuppressive drugs) within the past 2 years; however, replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroid replacement for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Overall survival;Disease Control Rate;Duration of Response;Safety; | — |
Countries
China
Contacts
Public ContactMeng Zhiqiang;Xie Jing
Fudan University Shanghai Cancer Center
Outcome results
None listed