HAI or IV of Adebrelimab, Combined With Bevacizumab and HAI of FOLFOX for Advanced Unresectable Hepatocellular Carcinoma

NCT06737913 | Recruiting Phase 2 DMC

• 2 other identifiers: B2024-588-01ChiCTR2400092928
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Adabrelimab (arterial or intravenous administration) combined with hepatic artery FOLFOX infusion chemotherapy and Bevacizumab as the first-line treatment of advanced stage hepatocellular carcinoma. Patients will be randomized 1:1 etither to receive hepatic arterial infusion(HAI) Adabrelimab group or IV Adabrelimab group, and both groups will receive HAI FOLFOX chemotherapy and IV Bevacizumab.

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Keywords

Hepatic arterial infusion (HAI); hepatic arterial infusion of FOLFOX chemotherapy; advanced unresectable hepatocellular carcinoma (HCC); Adebrelimab (ADE); Bevacizumab (Bev.); intravenous infusion (IV)

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Defined as the proportion of enrolled patients in each group who achieve either a complete response (CR) or partial response (PR) as the best response during the study, based on RECIST v1.1 criteria. Radiology imaging evaluations will be conducted every 6 weeks (or after every two treatment cycles) to assess treatment efficacy.

  6 weeks

Secondary Outcomes (7)

• Progression-free survival (PFS)

  36 months

• Overall survival(OS)

  36 months

• Time to progression

  36 months

• Disease control rate

  36 months

• Duration of response

  36 months

Study Arms (2)

HAIBrave-001 Arm 1

EXPERIMENTAL

Arm 1 to receive Hepatic arterial infusion (HAI) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.) + Hepatic artery infusion chemotherapy (HAIC) with FOLFOX regimen

Procedure: HAI Adebrelimab; Drug: intravenous infusion (IV) of Bevacizumab (Bev.); Procedure: HAIC with FOLFOX regimen; Drug: Adebrelimab and bevacizumab maintainance treatment

HAIBrave-001 Arm 2

EXPERIMENTAL

Intravenous infusion (IV) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.)+ HAIC with FOLFOX regimen

Drug: intravenous infusion (IV) of Adebrelimab (ADE); Drug: intravenous infusion (IV) of Bevacizumab (Bev.); Procedure: HAIC with FOLFOX regimen; Drug: Adebrelimab and bevacizumab maintainance treatment

Interventions

HAI Adebrelimab PROCEDURE

Hepatic arterial infusion (HAI) of Adebrelimab (ADE) (1200mg, IA, Q3W)

Also known as: HAI FOLFOX, IV Bevacizumab, IV Adebrelimab

HAIBrave-001 Arm 1

intravenous infusion (IV) of Adebrelimab (ADE) DRUG

intravenous infusion (IV) of Adebrelimab (ADE) (1200mg, IV, Q3W)

HAIBrave-001 Arm 2

intravenous infusion (IV) of Bevacizumab (Bev.) DRUG

intravenous infusion (IV) of Bevacizumab (Bev.) (15mg/kg, IV, Q3W)

HAIBrave-001 Arm 1; HAIBrave-001 Arm 2

HAIC with FOLFOX regimen PROCEDURE

HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2500 mg/m2 for 46 hours via hepatic artery Q4W)

HAIBrave-001 Arm 1; HAIBrave-001 Arm 2

Adebrelimab and bevacizumab maintainance treatment DRUG

The two arms continue the triple combination treatment up to 6 cycles and then received receive intravenous combination therapy of adebrelimab and bevacizumab for maintainance until disease progression or intolerable toxicity

HAIBrave-001 Arm 1; HAIBrave-001 Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the study and sign the informed consent form;
• Aged ≥18 years (calculated as of the date of signing the informed consent form);
• Diagnosed with hepatocellular carcinoma (HCC) by clinical or pathological means;
• Barcelona Clinic Liver Cancer (BCLC) stage C, with vascular/bile duct invasion or distant metastasis (excluding cases with Vp4-type tumor thrombus);
• No prior systemic therapy for HCC; or progression or residual lesions following prior local therapy for HCC (including but not limited to surgery, ablation, radiotherapy, or transarterial chemoembolization \[TACE\]), with an interval of at least one month between the last local treatment and enrollment;
• ECOG Performance Status (PS) score of 0-1 and Child-Pugh grade A or grade B with a score of 7;
• No history of autoimmune disease;
• An expected survival time of ≥3 months;
• At least one measurable lesion (per RECIST v1.1 criteria, the longest diameter of the measurable lesion on spiral CT scan must be ≥10 mm or the short axis of enlarged lymph nodes must be ≥15 mm; lesions previously treated locally can be considered target lesions if progression is confirmed per RECIST v1.1 criteria);
• Sufficient hematologic, hepatic, and renal function, with laboratory tests within the following parameters performed within one week prior to enrollment:
• Neutrophil count ≥1.5×10\^9/L;
• Platelet count ≥75×10\^9/L;
• Hemoglobin ≥90 g/L;
• Serum ALT and AST ≤5×upper limit of normal (ULN); ⑤ Serum creatinine ≤1.5×ULN; ⑥ International Normalized Ratio (INR) \<2.3, or prothrombin time ≤ULN+6 seconds; ⑦ Albumin ≥30 g/L;
• Total bilirubin ≤3×ULN.

You may not qualify if:

• Patients with a severe allergy to iodine contrast agents who are unable to undergo hepatic arterial infusion chemotherapy (HAIC);
• Use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes within one month prior to randomization;
• Active infections that cannot be effectively controlled;
• Severe gastroesophageal varices; untreated or incompletely treated gastroesophageal varices (with bleeding or high risk of bleeding);
• Presence of brain metastases or bone metastases requiring urgent surgical or radiotherapy intervention;
• Pregnant or suspected to be pregnant, or currently breastfeeding;
• Current use or recent use (within 10 days before the initiation of the study treatment) of aspirin (\>325 mg/day, maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel, and cilostazol;
• Thrombotic or embolic events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, or cerebral infarction) or pulmonary embolism, occurring within six months prior to the initiation of the study treatment;
• Congenital or acquired immunodeficiency;
• History of other malignant tumors;
• Any of the following conditions within 12 months prior to the initiation of the study: myocardial infarction, severe/unstable angina, or congestive heart failure;
• Renal insufficiency requiring dialysis;
• History of organ transplantation;
• Severe acute or chronic physical or mental illnesses or laboratory abnormalities that may increase study risks or interfere with result interpretation, rendering the patient unsuitable for enrollment.

Sponsors & Collaborators

• Henan Provincial People's Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Cancer Hospital of Guangxi Medical University: collaborator
• Sun Yat-sen University: lead
• First Affiliated Hospital of Fujian Medical University: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab; Infusions, Intravenous; Folfox protocol

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Central Study Contacts

Lujun Shen, M.D.

CONTACT

86-13560365452; shenlj@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A total of 76 patients (anticipated) will be randomized (1:1) to two arms to receive Hepatic arterial infusion (HAI) of Adebrelimab (ADE) (1200mg, IA, Q3W) and intravenous infusion (IV) of Bevacizumab (Bev.) (15mg/kg, IV, Q3W) plus HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2500 mg/m2 for 46 hours via hepatic artery Q4W) or intravenous infusion (IV) of Adebrelimab (ADE) (1200mg, IV, Q3W) and intravenous infusion (IV) of Bevacizumab (Bev.) (15mg/kg, IV, Q3W) plus HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2500 mg/m2 for 46 hours via hepatic artery, Q3W). The Two arms continue the triple combination treatment up to 6 cycles and then received receive intravenous combination therapy of adebrelimab and bevacizumab for maintainance until disease progression or intolerable toxicity.

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 17, 2024
• Study Start: January 3, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)