Adebrelimab (SHR-1316), Bevacizumab, Hepatocellular Carcinoma (HCC)
Conditions
Brief summary
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.
Interventions
PROCEDURETransarterial Chemoembolization (TACE)
Transarterial chemoembolization performed as first-line intervention for unresectable hepatocellular carcinoma.
DRUGHepatic 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).
DRUGAdebrelimab
Intravenous adebrelimab 1200 mg fixed dose, administered every 3 weeks (Q3W).
DRUGLow-dose Bevacizumab
Intravenous bevacizumab 7.5 mg/kg, administered every 3 weeks (Q3W).
Sponsors
Third Affiliated Hospital, Sun Yat-Sen University
Shanghai Shengdi Pharmaceutical Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 36 months from the first dose of study treatment | Percentage of participants achieving complete response (CR) or partial response (PR) as best overall response (BOR) according to RECIST v1.1 criteria, assessed by the investigator. |
| Progression-Free Survival (PFS) | From the first dose of study treatment until disease progression or death, up to 36 months | PFS is defined as the time from the first dose of study treatment to the first documented disease progression per RECIST v1.1 criteria or death from any cause, whichever occurs first, as assessed by the investigator. |
Contacts
CONTACTMingsheng Huang
Outcome results
None listed