Iparomlimab and Tuvonralimab as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With High Risk of Recurrence

NCT ID: NCT06954116

Last Updated: 2025-06-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2029-04-01

Brief Summary

The purpose of this study is to evaluate the impact of iparomlimab and tuvonralimab as preoperative neoadjuvant therapy on recurrence-free survival (RFS), along with its potential improvement in overall survival (OS), in patients with resectable hepatocellular carcinoma (HCC) at high risk of recurrence.

Detailed Description

CCGLC-017 is a prospective, open-label, single-arm, exploratory clinical study. This study primarily evaluates the impact of iparomlimab and tuvonralimab (QL1706) as preoperative neoadjuvant therapy on recurrence-free survival (RFS), with exploratory analysis of its potential benefits on overall survival (OS) in patients with resectable hepatocellular carcinoma (HCC) at high risk of recurrence. Enrolled patients will receive a single dose of iparomlimab and tuvonralimab within one week prior to surgery, followed by six cycles of iparomlimab and tuvonralimab therapy postoperatively.

Conditions

Resectable Hepatocellular Carcinoma With High Risk of Recurrence

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: Iparomlimab and Tuvonralimab

Patients will receive a single preoperative dose of Iparomlimab and Tuvonralimab (7.5 mg/kg) within one week prior to surgery. Partial hepatectomy will be performed at an appropriate interval following neoadjuvant therapy initiation. From the second week postoperatively, adjuvant therapy with six cycles of Iparomlimab and Tuvonralimab (7.5 mg/kg, Q3W) will be administered.

Group Type: EXPERIMENTAL

Iparomlimab and Tuvonralimab (QL1706)

Intervention Type: DRUG

Neoadjuvant phase: A single cycle of Iparomlimab and Tuvonralimab (7.5 mg/kg) will be administered within 1 week prior to surgery.

Adjuvant phase: Six cycles of Iparomlimab and Tuvonralimab (7.5 mg/kg, Q3W) will be initiated starting at 2 weeks postoperatively.

Partial hepatectomy

Intervention Type: PROCEDURE

Will be performed at an appropriate interval following neoadjuvant therapy initiation.

Interventions

Iparomlimab and Tuvonralimab (QL1706)

Neoadjuvant phase: A single cycle of Iparomlimab and Tuvonralimab (7.5 mg/kg) will be administered within 1 week prior to surgery.

Adjuvant phase: Six cycles of Iparomlimab and Tuvonralimab (7.5 mg/kg, Q3W) will be initiated starting at 2 weeks postoperatively.

Intervention Type: DRUG

Partial hepatectomy

Will be performed at an appropriate interval following neoadjuvant therapy initiation.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Hepatocellular carcinoma is proven on biopsy or confirmed by the presence of radiological hallmarks, according to the American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines.
• Aged 18 to 75 years.
• BCLC A/B, or BCLC C without extrahepatic metastasis.
• Suitable for radical surgery after evaluation by the hepatobiliary tumor MDT expert group.
• No distant metastasis confirmed by CT or MRI.
• No prior systemic anti-tumor treatment for hepatocellular carcinoma before the first dose.
• ECOG ≤ 2.
• Child-Pugh ≤ 7.
• Adequate organ and bone marrow function, with laboratory test values meeting the following requirements within 7 days prior to inclusion (no blood components, cell growth factors, albumin, or other intravenous or subcutaneous corrective treatment drugs are allowed within 14 days prior to obtaining laboratory tests):

1. Complete blood count: Absolute Neutrophil Count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin (HGB) ≥9.0 g/dL.

2. Liver function: Total Bilirubin (TBIL) ≤2×Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤5×ULN; Serum albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN.

C. Kidney function: Serum Creatinine (Cr) ≤ 1.5×ULN or Clearance of Creatinine (CCr) ≥50mL/min (Cockcroft-Gault formula); Urinalysis shows proteinuria <2+; For subjects with baseline urinalysis showing proteinuria ≥2+, a 24-hour urine collection should be performed and 24-hour urinary protein quantification <1g.

D. Coagulation function: International Normalized Ratio (INR) ≤2.3 or Prothrombin Time (PT) extension ≤6 seconds.

• Meet the criteria for resectable HCC with High Risk of Recurrence:

1. Multiple (≥2) tumors.

2. Segmental portal vein invasion (Vp1/Vp2).

3. CT/MRI imaging: gross classification: type II, III, IV.

• Estimated life expectancy of ≥12 weeks.
• Female subjects of childbearing age or male subjects whose sexual partners are of childbearing age need to take effective contraceptive measures during the entire treatment period and for 6 months after the last medication.
• Signed written informed consent, and able to comply with the visit and related procedures stipulated in the protocol.

Exclusion Criteria

• Histologically/cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.
• History of hepatic encephalopathy or liver transplantation.
• Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. Subjects with only radiologically detected minimal pleural effusion, ascites, or pericardial effusion without symptoms can be enrolled.
• Acute or chronic active hepatitis B or C infection, with hepatitis B virus (HBV) DNA >2000IU/ml or 10^4 copies/ml; hepatitis C virus (HCV) RNA >10^3 copies/ml; co-positive for hepatitis B surface antigen (HbsAg) and anti-HCV antibody. Subjects who meet the above criteria after antiviral treatment with nucleoside analogs can be enrolled.
• History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months. Subjects assessed by the investigator to be at high risk of bleeding.
• Any life-threatening bleeding event within the past 3 months, including those requiring blood transfusion, surgery or local treatment, or continuous drug treatment.
• History or current diagnosis of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of lung function, and other lung diseases.
• Active pulmonary tuberculosis, currently receiving anti-tuberculosis treatment, or received anti-tuberculosis treatment within 1 year prior to the first dose.
• Active autoimmune disease requiring systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) is allowed. History of primary immunodeficiency. Patients with only autoantibody positivity need to be confirmed by the investigator whether there is an autoimmune disease.
• History of arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolic events. Exceptions are made for thrombosis formation related to implanted venous infusion ports or catheters, or superficial vein thrombosis that has stabilized after routine anticoagulation treatment. Preventive use of low-dose low molecular weight heparin (such as enoxaparin 40 mg/day) is allowed.
• Continuous use of aspirin (>325 mg/day) or other known platelet function inhibitors such as clopidogrel or ticlopidine for 10 days within 2 weeks prior to the first dose.
• Uncontrolled hypertension, with systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
• Major surgery (craniotomy, thoracotomy, or laparotomy) or unhealed wound, ulcer, or fracture within 4 weeks prior to the first dose. Minor surgical procedures or tissue biopsy within 7 days prior to the first dose, excluding venous puncture for the purpose of intravenous infusion, are excluded.
• Uncontrolled/uncorrectable metabolic disorders or other non-malignant organ diseases or systemic diseases or secondary reactions to cancer, which can lead to higher medical risk and/or uncertainty in survival evaluation, or other conditions judged by the investigator to be unsuitable for enrollment.
• History of gastrointestinal perforation and/or fistula within the previous 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Qilu Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ze-yang Ding, MD

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ze-yang Ding, M.D.

Role: STUDY_CHAIR

Tongji Hospital

Locations

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Countries

China

Central Contacts

Ze-yang Ding, M.D.

Role: CONTACT

zyding@tjh.tjmu.edu.cn

+8613407156200

Han Gao

Role: CONTACT

gh1023606887@163.com

+8617730117747

Facility Contacts

Ze-yang Ding, M.D.

Role: primary

zyding@tjh.tjmu.edu.cn

+8613407156200

Han Gao

Role: backup

gh1023606887@163.com

+8617730117747

Other Identifiers

TJ-IRB202503089

Identifier Type: -

Identifier Source: org_study_id