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

NCT06954116 | Not Yet Recruiting Phase 2

• 1 other identifier: TJ-IRB202503089
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Resectable Hepatocellular Carcinoma With High Risk of Recurrence

Keywords

Hepatocellular Carcinoma; Neoadjuvant Therapy; Iparomlimab and Tuvonralimab; Immunotherapy; Anti-recurrence

Outcome Measures

Primary Outcomes (1)

• Recurrence-Free Survival (RFS)

  The duration will be calculated from the date of achieving complete response (CR) after surgery to the first documented occurrence of intrahepatic or extrahepatic HCC recurrence, or death from any cause, whichever comes first.

  From the date of achieving complete response (CR) after surgery until the date of first documented recurrence or death from any cause, assessed up to 24 months post-surgery.

Secondary Outcomes (10)

• Overall Survival (OS)

  from the date of first treatment to the date of death from any cause, assessed up to 5 years

• Major Pathological Response (MPR)

  Intraoperative frozen section assessment and final postoperative pathology (assessed within 4 weeks after surgery).

• Investigator-Assessed Recurrence-Free Survival (RFS)

  From treatment initiation until the date of first documented HCC recurrence or death from any cause, whichever occurs first, assessed up to 24 months.

• Time to Recurrence (TTR)

  From treatment initiation until the date of first documented HCC recurrence, assessed up to 24 months.

• IRF-Assessed RFS Rate at 12 and 24 Months

  At 12 and 24 months post-treatment.

Study Arms (1)

Experimental: Iparomlimab and Tuvonralimab

EXPERIMENTAL

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.

Drug: Iparomlimab and Tuvonralimab (QL1706); Procedure: Partial hepatectomy

Interventions

Iparomlimab and Tuvonralimab (QL1706) 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.

Experimental: Iparomlimab and Tuvonralimab

Partial hepatectomy PROCEDURE

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

Experimental: Iparomlimab and Tuvonralimab

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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:
• Multiple (≥2) tumors.
• Segmental portal vein invasion (Vp1/Vp2).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tongji Hospital: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

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

Wuhan, Hubei, 430030, China

Location

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

Study Officials

• Ze-yang Ding, M.D.

  Tongji Hospital

  STUDY CHAIR

Central Study Contacts

Ze-yang Ding, M.D.

CONTACT

+8613407156200; zyding@tjh.tjmu.edu.cn

Han Gao

CONTACT

+8617730117747; gh1023606887@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: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: May 1, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: June 13, 2025

Record last verified: 2025-06

Locations

CN (1)