Ipilimumab N01 Combined With Sintilimab, Bevacizumab Biosimilar, and Hepatic Arterial Infusion Chemotherapy as Conversion Therapy for Unresectable Intermediate-Advanced Hepatocellular Carcinoma

NCT07560488 | Recruiting Phase 2

• 1 other identifier: SIBH-HCC
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Conversion therapy for unresectable intermediate-advanced hepatocellular carcinoma (uHCC) has evolved from systemic therapy to combined local-systemic approaches, but current regimens still have limited surgical conversion rates. This prospective, single-arm phase II study evaluates a combination regimen of PD-1 inhibitor (sintilimab) plus CTLA-4 inhibitor (ipilimumab N01), bevacizumab biosimilar, and HAIC for patients with initially unresectable intermediate-advanced HCC. The primary goal is to achieve a higher surgical conversion rate with manageable safety

Conditions

Conversion Therapy; HCC - Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Conversion resection rate

  The percentage of initially unresectable patients who underwent curative resection after protocol-specified conversion therapy.

  up to 1 year

Secondary Outcomes (5)

• Objective response rate

  up to 1 year

• R0 Resection Rate

  up to 1 year

• Pathological Complete Response

  up to 1 year

• Overall survival

  up to 3 years

• Treatment-Related Adverse Events (TRAE)

  up to 3 years

Study Arms (1)

Ipilimumab N01+Sintimab+Bevacizumab+HAIC

EXPERIMENTAL

Drug: Bevacizumab Biosimilar IBI305; Drug: ipilimumab N01; Drug: Sintilimab; Drug: HAIC

Interventions

Bevacizumab Biosimilar IBI305 DRUG

7.5 mg/kg, iv, q3w, 3 cycles (discontinue 1 week before surgery)

Ipilimumab N01+Sintimab+Bevacizumab+HAIC

ipilimumab N01 DRUG

3mg/kg, iv, q6w, 2 cycles

Ipilimumab N01+Sintimab+Bevacizumab+HAIC

Sintilimab DRUG

200mg, iv, q3w, 4 cycles

Ipilimumab N01+Sintimab+Bevacizumab+HAIC

HAIC DRUG

FOLFOX-HAIC, q3w, 4 cycles

Ipilimumab N01+Sintimab+Bevacizumab+HAIC

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be signed prior to initiation of any study-related procedures;
• Age ≥ 18 years, and ≤75 years, regardless of gender;
• Clinically diagnosed or histologically/cytologically confirmed hepatocellular carcinoma (HCC) according to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition);
• No prior anti-tumor therapy for HCC before study treatment
• Unresectable locally advanced or advanced HCC (CNLC Stage IIa-IIIb).
• Expected overall survival \> 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Child-Pugh score class A or B
• Adequate organ function defined by the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L without granulocyte colony-stimulating factor support within 14 days;
• Platelet count ≥ 80×10⁹/L without transfusion within 14 days;
• Hemoglobin \> 9 g/dL without transfusion or erythropoietin within 14 days;
• Total bilirubin ≤ 1.5×upper limit of normal (ULN); or total bilirubin \> ULN with direct bilirubin ≤ ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3×ULN;
• Serum creatinine ≤ 1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 60 mL/min;

You may not qualify if:

• Target disease exceptions:
• Fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular-cholangiocarcinoma.
• Recurrent HCC.
• Clinically diagnosed hepatic encephalopathy within the most recent 6 months.
• Autoimmune hepatitis (requiring liver biopsy confirmation);
• History of organ transplantation or history of hepatic encephalopathy;
• Diffuse hepatocellular carcinoma;
• Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage;
• History of any renal disease or nephrotic syndrome.
• Variceal bleeding (esophageal or gastric varices) due to portal hypertension within the past 6 months;severe (Grade 3) varices on endoscopy within 3 months before first dose;evidence of portal hypertension (e.g., splenomegaly \>10 cm in longest diameter with platelets \<100×10⁹/L on imaging) with high bleeding risk as assessed by the investigator;
• 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.Excluded are catheter-related or port-related thrombosis or superficial venous thrombosis that is stable with standard anticoagulation;
• Severe bleeding tendency or coagulopathy, or ongoing thrombolytic therapy;
• Prophylactic low-molecular-weight heparin (e.g., enoxaparin 40 mg daily) is permitted; vitamin K antagonists (e.g., warfarin) are excluded;
• Long-term use of anti-platelet agents including aspirin, dipyridamole, clopidogrel, or other similar medications;
• Uncontrolled hypertension despite optimal medical management (systolic BP \>140 mmHg or diastolic BP \>90 mmHg); history of hypertensive crisis or hypertensive encephalopathy;

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Cancer Hospital Airport Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

sintilimab

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

Huikai Li, Prof.

CONTACT

+8618526812877; 18526812877@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: May 1, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)