A Prospective, Randomized Study of TACE Combined With Sintilimab, Bevacizumab, and Ipilimumab N01 Treating Advanced HCC

NCT07422753 | Recruiting Phase 2

• 1 other identifier: 2025-1454
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability, and preliminary efficacy of a combination therapy involving TACE, sintilimab, bevacizumab, and ipilimumab N01 for the treatment of advanced hepatocellular carcinoma (HCC). It also aims to explore the potential synergistic mechanisms of this combination. The main questions it aims to answer are: Is the combination of TACE, sintilimab, bevacizumab, and ipilimumab N01 effective and safe for patients with advanced HCC? How do different sequencing schedules of ipilimumab N01 compare in terms of safety and efficacy? What potential biomarkers can predict treatment response? Researchers will compare three different treatment groups: Group A: Receives TACE and a single dose of ipilimumab N01 administered 3 weeks after the first dose of sintilimab and bevacizumab. Group B: Receives TACE and a single dose of ipilimumab N01 administered concurrently with the first dose of sintilimab and bevacizumab. Group C: Receives TACE, sintilimab and bevacizumab (without ipilimumab N01). Participants will: Be screened for eligibility and be randomly assigned to one of the three treatment groups. Receive the assigned study treatment according to their group's schedule. Undergo regular clinic visits for safety checkups, tumor imaging assessments, and response evaluation using RECIST v1.1 and RECICL criteria. Provide biological samples for exploratory biomarker analysis, including: Peripheral blood at baseline and before each treatment cycle (every 3 weeks). Tumor biopsy specimens at baseline and 6 weeks after the first treatment. Surgical specimens if the patient undergoes conversion surgery. Participate in follow-up visits: A safety follow-up visit 30 days after the last study drug dose or before starting new anti-cancer therapy. Subsequent survival follow-up contacts every 90 days to collect information on survival status and any subsequent anti-cancer treatments.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (2)

• ORR of Participants Assessed by RECIST1.1

  Up to 6 months after randomization

• Occurrence of Immune-Related Adverse Events Assessed by CTCAE v6.0

  From the start of treatment to 6 months after the end of treatment

Secondary Outcomes (6)

• DCR of Participants Assessed by RECIST1.1

  Up to 6 months after randomization

• ORR of Participants Assessed by RECICL

  Up to 6 months after randomization

• PFS of Participants Assessed by RECIST1.1

  Until disease progression

• Overall survival(OS) of Participants

  Up to 24 months after randomization

• DOR of Participants Assessed by RECIST1.1

  Up to 24 months after randomization

Study Arms (3)

αCTLA-4 Combined with Delay

EXPERIMENTAL

Receives a single dose of ipilimumab N01 administered 3 weeks after the first dose of sintilimab and bevacizumab

Drug: placebo; Drug: CTLA-4 Antibody(ipilimumab N01)

αCTLA-4 Combined Concurrently

EXPERIMENTAL

Receives a single dose of ipilimumab N01 administered concurrently with the first dose of sintilimab and bevacizumab

Drug: placebo; Drug: CTLA-4 Antibody(ipilimumab N01)

No αCTLA-4 Combined

PLACEBO COMPARATOR

Receives sintilimab and bevacizumab without ipilimumab N01

Drug: placebo

Interventions

placebo DRUG

The patient would receive placebo administered concurrently or 3 weeks after the first dose of sintilimab, in combination with sintilimab (200mg IV, Q3W), bevacizumab (15mg/kg IV, Q3W), and TACE.

No αCTLA-4 Combined; αCTLA-4 Combined Concurrently; αCTLA-4 Combined with Delay

CTLA-4 Antibody(ipilimumab N01) DRUG

The patient would receive a single dose of ipilimumab N01 (3mg/kg IV) administered concurrently or 3 weeks after the first dose of sintilimab, in combination with sintilimab (200mg IV, Q3W), bevacizumab (15mg/kg IV, Q3W), and TACE.

Also known as: IBI310

αCTLA-4 Combined Concurrently; αCTLA-4 Combined with Delay

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign and date a written informed consent form prior to the implementation of any trial-related procedures.
• Patients with clinically confirmed unresectable or metastatic hepatocellular carcinoma (HCC).
• Male or female, ≥18 years old, ≤75 years old.
• ECOG Performance Status score of 0\~1.
• Expected survival time \>3 months.
• Barcelona Clinic Liver Cancer (BCLC) Stage B or C for unresectable HCC.
• Suitable for Transarterial Chemoembolization (TACE) treatment.
• Child-Pugh score ≤7.
• At least one measurable lesion according to RECIST 1.1 criteria.

You may not qualify if:

• Previous histological/cytological confirmation of HCC with fibrolamellar, sarcomatoid, or cholangiocarcinoma components.
• History of liver transplantation or hepatic encephalopathy.
• Diffuse liver cancer.
• Inability to tolerate TACE or prior history of TACE treatment.
• Prior treatment with Transarterial Chemoembolization (TACE), Transarterial Embolization (TAE), or Transarterial Radioembolization (TARE).
• Prior systemic anti-tumor therapy or radiotherapy for HCC.
• Portal vein main trunk tumor thrombus without adequate collateral circulation, or concurrent involvement of the superior mesenteric vein; inferior vena cava tumor thrombus.
• Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage.
• Any history of renal disease or nephrotic syndrome.
• History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months; presence of severe (Grade 3) varices on endoscopy known within 3 months prior to first dose; evidence of portal hypertension (including splenomegaly on imaging) with high risk of bleeding as assessed by the investigator.
• Any life-threatening bleeding event within the past 3 months, requiring transfusion, surgery, local therapy, or continuous medication.
• 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. Except for catheter-related thrombosis from implanted ports or superficial venous thrombosis if stable under routine anticoagulation.
• Significant bleeding tendency or coagulopathy, or undergoing thrombolytic therapy.
• Prophylactic use of low-dose low molecular weight heparin (e.g., enoxaparin 40 mg/day) is allowed, but not vitamin K antagonists (e.g., warfarin).
• Requirement for long-term use of platelet function inhibitors such as aspirin, dipyridamole, or clopidogrel.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

the Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Zhongquan Sun

CONTACT

86+13732233417; sunzq@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 20, 2026
• Study Start: March 25, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-02

Locations

CN (1)