HCC
Conditions
Interventions
Test group:TACE: On-demand treatment
TKI drugs: Selected by the investigator.
Iparomlimab and Tuvonralimab: 5 mg/kg, IV infusion, every 3 weeks
Sponsors
The First Affiliated Hospital of Bengbu Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Sign a written informed consent form; 2. Age >= 18 years, male or female; 3. Subjects with pathologically, cytologically, or radiologically confirmed advanced hepatocellular carcinoma (HCC); 4. Subjects must have progressed after receiving immunotherapy, including anti-PD-1/PD-L1 monoclonal antibody therapy as monotherapy or in combination with other checkpoint inhibitors or other therapies; 5. Subjects with BCLC stage B/C hepatocellular carcinoma; 6. Child-Pugh liver function grade: A–B (= 3 months; 10. Major organ function levels must meet the following requirements within 3 days prior to first dose (no supportive therapy, such as any blood component, allowed within 14 days prior to first dose): a) Absolute neutrophil count >= 1.5 × 10^9/L; b) Platelets >= 50 × 10^9/L; c) Hemoglobin >= 90 g/L; d) Serum albumin >= 30 g/L; e) AST and ALT 1.5 × ULN, calculated creatinine clearance (CLcr) >= 50 mL/min using the Cockcroft-Gault equation; h) Proteinuria = 2+, perform 24-hour urine protein quantification; eligibility if = 1 g); i) International Normalized Ratio (INR) <= 1.5; Activated Partial Thromboplastin Time (APTT) <= 1.5 × ULN; 11. For patients with hepatitis B virus (HBV) infection: must have received at least 1 week of anti-HBV therapy prior to enrollment and be willing to undergo antiviral therapy throughout the study period; patients with hepatitis C virus (HCV) RNA positivity must receive antiviral therapy according to treatment guidelines and have liver function within CTCAE Grade 1 elevation; 12. Women of childbearing potential must have a negative pregnancy test (ß-HCG) prior to treatment initiation. Women of childbearing potential and males (engaging in sexual intercourse with women of childbearing potential) must agree to use contraception during treatment and for 6 months after the last dose. 13. Patients deemed likely to benefit by the investigator.
Exclusion criteria
Exclusion criteria: 1. Known hepatobiliary duct cell carcinoma, sarcomatoid HCC, mixed cell carcinoma, or fibrolamellar carcinoma; 2. Active malignancies other than HCC within the past 5 years or concurrently present. Cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, or carcinoma in situ of the breast are permissible for inclusion; 3. Unresolved toxicity (excluding alopecia, non-clinically significant, and asymptomatic laboratory abnormalities) from prior antitumor therapy that has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 prior to the first study treatment dose; 4. Permanent discontinuation of immune checkpoint inhibitors due to any Grade >=3 Common Terminology Criteria for Adverse Events (CTCAE) adverse events or other immune-related toxicities during prior therapy; 5. Child-Pugh Class C liver function; 6. Liver tumor burden exceeding 75% of the entire liver, or concomitant inferior vena cava or superior mesenteric vein tumor thrombus; 7. Contraindications to TKI drugs, immune checkpoint inhibitors, or transarterial chemoembolization (TACE); 8. Severe comorbidities, including significant cardiac, pulmonary, renal, or coagulation disorders; major cardiovascular conditions (e.g., unstable arrhythmias, unstable angina, myocardial infarction); 9. Pregnant or lactating women; 10. Systemic infection or other severe infection requiring >7 days of intravenous antibiotics within 2 weeks prior to first dose, or unexplained fever >38.5°C (68.5°F) during screening or pre-enrollment (excluding fever deemed tumor-related by the investigator); 11. Diagnosed with immunodeficiency or having received systemic steroid therapy, any other form of immunosuppressive therapy, or immunomodulatory therapy within 7 days prior to the first dose of study drug; 12. Significant clinically relevant bleeding events or established bleeding tendencies within 6 months prior to enrollment, such as gastrointestinal bleeding, severe esophageal or gastric varices, hemorrhagic gastric ulcer, or vasculitis. If fecal occult blood is positive at baseline, repeat testing is permitted; if still positive, gastroscopy is required; 13. Known hereditary or acquired bleeding disorders (e.g., coagulation disorders) or thrombotic tendencies, such as hemophilia, coagulation mechanism defects, thrombocytopenia, etc.; currently receiving full-dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (low-dose aspirin for prophylaxis is permitted); 14. Arterial thromboembolic events within 6 months prior to enrollment, including cerebrovascular accidents (such as transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis of CTCAE grade 3 or higher, pulmonary embolism, etc.; 15. Symptomatic central nervous system (CNS) metastases; 16. Active or potentially recurrent autoimmune diseases; 17. History and/or current interstitial lung disease, pneumoconiosis, or radiation pneumonitis deemed clinically significant by the investigator, or severe pulmonary impairment that may interfere with detection and management of suspected drug-related pulmonary toxicity; 18. HIV-positive patients; known history of anti-tuberculosis therapy within one year prior to first study treatment; known active syphilis infection; 19. Clinical symptom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression free survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate, ORR;disease control rate, DCR;Duration of relief, DOR;Overall survival, OS;adverse event, AE; | — |
Countries
China
Contacts
Public ContactMu Yuan
The First Affiliated Hospital of Bengbu Medical University
Outcome results
None listed