Efficacy and Safety of Low-dose Bevacizumab Plus Adebrelimab Combined With Transarterial Chemoembolization Followed by Hepatic Arterial Infusion Chemotherapy (TACE-HAIC) as First-line Treatment for Unresectable Hepatocellular Carcinoma: A Single-arm Phase 2 Trial

Inclusion criteria

Willing to participate and provide written informed consent. Age ≥ 18 years (on the day of signing informed consent). Histologically or cytologically confirmed hepatocellular carcinoma (HCC), or clinical diagnosis of HCC according to AASLD criteria in patients with cirrhosis.

Eligible for TACE, including BCLC stage B or C, with unresectable HCC (excluding PVTT-Vp4 and extrahepatic metastasis).

No prior systemic therapy for HCC. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Child-Pugh score A or B7. No history of autoimmune disease. Life expectancy ≥ 3 months. At least one measurable lesion per RECIST v1.1 (spiral CT scan long diameter ≥ 10 mm or short diameter of enlarged lymph node ≥ 15 mm; lesions previously treated with locoregional therapy can be considered target lesions only if progression per RECIST v1.1 is clearly documented).

Adequate hematologic, hepatic, and renal function within 7 days prior to enrollment:

Neutrophils ≥ 1.5 × 10⁹/L Platelets ≥ 50 × 10⁹/L Hemoglobin ≥ 90 g/L ALT/AST ≤ 5 × ULN Serum creatinine ≤ 1.5 × ULN INR < 2.3 or prothrombin time ≤ ULN + 6 seconds Albumin ≥ 30 g/L Total bilirubin ≤ 3 × ULN Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must not be lactating; they and male participants must agree to use effective contraception during the study and for 6 months after study completion

Exclusion criteria

Known cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma, or fibrolamellar carcinoma. Active malignancy other than HCC within 5 years, excluding cured localized tumors such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, or breast carcinoma in situ.

Severe allergy to iodine contrast precluding TACE-HAIC. Use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes within 1 month prior to enrollment.

Active uncontrolled infection. Severe gastroesophageal varices; untreated or incompletely treated varices (with bleeding or high bleeding risk).

Brain metastases or bone metastases requiring urgent surgical or radiation intervention.

Pregnant, suspected pregnancy, or breastfeeding. Current or recent use (within 10 days prior to study treatment) of aspirin (> 325 mg/day) or dipyridamole, ticlopidine, clopidogrel, or cilostazol.

Thromboembolic events within 6 months prior to study treatment, including cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.

Congenital or acquired immunodeficiency. Myocardial infarction, severe/unstable angina, or congestive heart failure within 12 months prior to study start.

Renal insufficiency requiring dialysis. History of organ transplantation. Any other serious acute or chronic medical or psychiatric condition, or laboratory abnormality that would increase the risk of study participation or interfere with interpretation of results.