Hepatocellular carcinoma
Conditions
Interventions
Intervention group:Ipilimumab N01 in combination with sintilimab and small molecule tyrosine kinase inhibitors
Ipilimumab N01 1mg/kg Q3W intravenous infusion is administered on the first day of each t
Sponsors
The First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Sign written informed consent before any study-related procedures are performed. 2. Age between 18 and 75 years. 3. Hepatocellular carcinoma confirmed by imaging or histology, with at least one measurable lesion. 4. Disease progression after prior first-line systemic therapy with anti-PD-1/PD-L1 combined with bevacizumab as the core regimen. 5. Child-Pugh class A or B. 6. ECOG performance status 0 or 1. 7. Expected survival >=3 months. 8. Adequate organ function, with the subject meeting the following laboratory criteria before enrollment: (1) Absolute neutrophil count (ANC) >=1.5×10^9/L within the past 14 days without granulocyte colony-stimulating factor use; (2) Platelet count >=100×10^9/L within the past 14 days without blood transfusion; (3) Hemoglobin >9 g/dL within the past 14 days without blood transfusion or erythropoietin use; (4) Total bilirubin 1.5×ULN but direct bilirubin =60 mL/min; (7) Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) <=1.5×ULN; (8) Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range may also be enrolled; (9) Cardiac enzyme levels within the normal range (isolated laboratory abnormalities deemed clinically insignificant by the investigator's comprehensive judgment are also allowed for enrollment). 9. For female subjects of childbearing potential, a urine or serum pregnancy test must be performed within 3 days before the first study drug administration (Cycle 1 Day 1) and the result must be negative. If the urine pregnancy test cannot be confirmed as negative, a serum pregnancy test is required. Non-childbearing potential is defined as postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy; if there is a risk of pregnancy, all subjects (male or female) must use contraceptive methods with a failure rate of <1% per year throughout the treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).
Exclusion criteria
Exclusion criteria: 1. Pathologically confirmed non-hepatocellular carcinoma subtypes, including intrahepatic cholangiocarcinoma (ICC), mixed hepatocellular-cholangiocarcinoma (HCC-ICC), hepatoblastoma, undifferentiated carcinoma, and sarcomatoid carcinoma. 2. Diagnosis of other malignancies other than hepatocellular carcinoma within 5 years before the first dose (excluding basal cell carcinoma, squamous cell carcinoma of the skin, well-differentiated thyroid carcinoma, and carcinoma in situ that have been curatively resected). 3. Currently participating in an interventional clinical study, or having received other investigational drugs within 4 weeks before the first dose. 4. Prior systemic antitumor therapy. 5. Received systemic treatment with Chinese patent medicines with antitumor indications or immunomodulatory agents (including thymosin, interferon, interleukin, except for local use to control pleural effusion) within 2 weeks before the first dose. 6. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years before the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) is not considered systemic therapy. 7. Receiving systemic glucocorticoid therapy (excluding intranasal, inhaled, or other topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first dose. Note: Physiological doses of glucocorticoids (<=10 mg/day of prednisone or equivalent) are permitted. 8. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation. 9. Known allergy to any drug used in this study. 10. Failure to fully recover from toxicities and/or complications caused by any prior intervention before the start of treatment (i.e., <= grade 1 or returned to baseline, excluding fatigue or alopecia). 11. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive). 12. Untreated active hepatitis B (defined as HBsAg positive with detectable HBV-DNA copy number above the upper limit of normal of the testing laboratory at the study center). Note: Subjects with hepatitis B meeting the following criteria may also be enrolled: HBV viral load <1000 copies/mL (200 IU/mL) before the first dose, and subjects should receive anti-HBV therapy during the entire study chemotherapy period to prevent viral reactivation. For subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is needed. 13. Subjects with active HCV infection (HCV antibody positive with HCV-RNA level above the lower limit of detection). 14. Received live vaccine within 30 days before the first dose (Cycle 1, Day 1). Note: Inactivated influenza vaccines for injection against seasonal influenza are permitted within 30 days before the first dose; however, live attenuated influenza vaccines administered intranasally are not permitted. 15. Pregnant or breastfeeding women. 16. Presence of any severe or uncontrolled systemic disease, for example: (1) Significant and severe uncontrolled abnormalities in rhythm, conduction, or morphology on resting electrocardiogram, such as complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmias, or atrial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;Safety;Progression-free survival period;Duration of Response (DOR);Time to remission; | — |
Countries
China
Contacts
Public ContactZhu Xiaoli
The First Affiliated Hospital of Soochow University
Outcome results
None listed