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

Обзор

his is a single-arm, phase II clinical study evaluating the efficacy and safety of low-dose bevacizumab (7.5 mg/kg, Q3W) plus adebrelimab (1200 mg, Q3W) combined with transarterial chemoembolization (TACE) followed by hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen as first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). Eligible participants will receive TACE followed by HAIC (oxaliplatin, leucovorin, and fluorouracil) and subsequent intravenous administration of adebrelimab and low-dose bevacizumab every 3 weeks. The primary endpoint is objective response rate (ORR) assessed by investigators per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. A total of 38 participants will be enrolled using Simon's two-stage optimal design (alpha=0.05, power=0.8). The study is sponsored by the Third Affiliated Hospital of Sun Yat-sen University. Adebrelimab is provided free of charge for two years by Shanghai Shengdi Pharmaceutical Co., Ltd.

Вмешательства

• Процедура Transarterial Chemoembolization (TACE)
  Transarterial chemoembolization performed as first-line intervention for unresectable hepatocellular carcinoma.
• Препарат Hepatic Arterial Infusion Chemotherapy (HAIC, FOLFOX)
  Hepatic arterial infusion chemotherapy with FOLFOX regimen (oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² bolus then 2400 mg/m² continuous infusion over 24 hours).
• Препарат Adebrelimab
  Intravenous adebrelimab 1200 mg fixed dose, administered every 3 weeks (Q3W).
• Препарат Low-dose Bevacizumab
  Intravenous bevacizumab 7.5 mg/kg, administered every 3 weeks (Q3W).

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: Up to 36 months from the first dose of study treatment]
• Progression-Free Survival (PFS) [Срок оценки: From the first dose of study treatment until disease progression or death, up to 36 months]

Критерии участия

Критерии включения

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

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07543783 · II2026-037-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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