💬In plain words
What the trial is, and whether it could suit you
Conversion therapy for unresectable intermediate-advanced hepatocellular carcinoma (uHCC) has evolved from systemic therapy to combined local-systemic approaches, but current regimens still have limited surgical conversion rates.
This prospective, single-arm phase II study evaluates a combination regimen of PD-1 inhibitor (sintilimab) plus CTLA-4 inhibitor (ipilimumab N01), bevacizumab biosimilar, and HAIC for patients with initially unresectable intermediate-advanced HCC. The primary goal is to achieve a higher surgical conversion rate with manageable safety
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* Written informed consent must be signed prior to initiation of any study-related procedures;
* Age ≥ 18 years, and ≤75 years, regardless of gender;
* Clinically diagnosed or histologically/cytologically confirmed hepatocellular carcinoma (HCC) according to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition);
* No prior anti-tumor therapy for HCC before study treatment
* Unresectable locally advanced or advanced HCC (CNLC Stage IIa-IIIb).
* Expected overall survival \> 6 months.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Child-Pugh score class A or B
* Adequate organ function defined by the following laboratory parameters:
1. Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L without granulocyte colony-stimulating factor support within 14 days;
2. Platelet count ≥ 80×10⁹/L without transfusion within 14 days;
3. Hemoglobin \> 9 g/dL without transfusion or erythropoietin within 14 days;
4. Total bilirubin ≤ 1.5×upper limit of normal (ULN); or total bilirubin \> ULN with direct bilirubin ≤ ULN;
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3×ULN;
6. Serum creatinine ≤ 1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 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 normal limits. Subjects with abnormal baseline TSH but normal total T3 (or FT3) and FT4 are also eligible;
9. Myocardial enzymes within normal limits; isolated laboratory abnormalities deemed clinically insignificant by the investigator are permitted.
* Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first dose of study drug (Day 1 of Cycle 1). A blood pregnancy test is required if the urine test is inconclusive; They must agree to use adequate contraception during the study period and for 8 weeks after the last dose of study drug;
* All subjects (male or female) of reproductive potential must use a highly effective contraceptive method with an annual failure rate \< 1% throughout treatment and for 120 days after the last dose of immunotherapy or 180 days after the last dose of chemotherapy, whichever is longer.
Exclusion Criteria:
* Target disease exceptions:
1. Fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular-cholangiocarcinoma.
2. Recurrent HCC.
3. Clinically diagnosed hepatic encephalopathy within the most recent 6 months.
* Autoimmune hepatitis (requiring liver biopsy confirmation);
* History of organ transplantation or history of hepatic encephalopathy;
* Diffuse hepatocellular carcinoma;
* Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage;
* History of any renal disease or nephrotic syndrome.
* Variceal bleeding (esophageal or gastric varices) due to portal hypertension within the past 6 months;severe (Grade 3) varices on endoscopy within 3 months before first dose;evidence of portal hypertension (e.g., splenomegaly \>10 cm in longest diameter with platelets \<100×10⁹/L on imaging) with high bleeding risk as assessed by the investigator;
* Arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other severe thromboembolism.Excluded are catheter-related or port-related thrombosis or superficial venous thrombosis that is stable with standard anticoagulation;
* Severe bleeding tendency or coagulopathy, or ongoing thrombolytic therapy;
* Prophylactic low-molecular-weight heparin (e.g., enoxaparin 40 mg daily) is permitted; vitamin K antagonists (e.g., warfarin) are excluded;
* Long-term use of anti-platelet agents including aspirin, dipyridamole, clopidogrel, or other similar medications;
* Uncontrolled hypertension despite optimal medical management (systolic BP \>140 mmHg or diastolic BP \>90 mmHg); history of hypertensive crisis or hypertensive encephalopathy;
* Symptomatic congestive heart failure (NYHA Class II-IV); symptomatic or poorly controlled arrhythmia; congenital long QT syndrome or QTcF \>500 ms at screening;
* History of gastrointestinal perforation and/or fistula within the past 6 months; history of bowel obstruction (including partial obstruction requiring parenteral nutrition); extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea;
* Major surgical procedure (cranial, thoracic, or abdominal) within 4 weeks before first dose, or non-healing wounds, ulcers, or fractures.Core needle biopsy or minor surgery within 7 days before first dose is excluded, except for venous catheter placement for intravenous access;
* History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-induced pneumonitis, or severe pulmonary dysfunction;
* Acute or chronic active hepatitis B or C infection:HBV DNA \>2000 IU/mL or 10⁴ copies/mL;HCV RNA \>10³ copies/mL;coinfection with HBsAg and anti-HCV antibody;
* Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year before first dose;
* Human immunodeficiency virus (HIV) infection (positive HIV 1/2 antibody) or active syphilis;
* Active or poorly controlled severe infection; severe infection requiring hospitalization (including sepsis, bacteremia, or severe pneumonia) within 4 weeks before first dose;
* Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years before first dose.Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal/pituitary insufficiency) is permitted.History of primary immunodeficiency.Subjects with isolated positive autoimmune antibodies will be evaluated at the investigator's discretio
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