PD-1/IL-2 Bispecific Antibody as Neoadjuvant Therapy for Early Recurrent Hepatocellular Carcinoma After Curative Hepatectomy

Starting soon · Phase 2

Conditions studied: Hepatocellular Carcinoma (HCC)

In brief

This is a single-arm, phase II clinical study designed to evaluate the efficacy and safety of a recombinant PD-1/IL-2 bispecific antibody, as neoadjuvant therapy in hepatocellular carcinoma (HCC) patients who experienced early recurrence after curative hepatectomy and were suitable for repeat surgical resection. A total of approximately 30 eligible participants are planned to be enrolled. All patients will receive neoadjuvant treatment with PD-1/IL-2 bispecific antibody for 3 cycles. Curative re-resection will be performed 2 to 7 weeks after the last dose of PD-1/IL-2 bispecific antibody for patients with resectable lesions confirmed by imaging assessment. Tumor evaluation will be conducted per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) throughout the study. Postoperative pathological assessment and long-term follow-up will be implemented after surgery. The primary endpoint is the major pathological response (MPR) rate. Secondary endpoints include complete pathological response (pCR) rate, event-free survival (EFS), overall survival (OS), R0 resection rate, objective response rate (ORR), disease control rate (DCR), and the safety and tolerability profile . Exploratory endpoints aim to analyze the correlation between biomarkers (e.g., PD-L1 expression, tumor microenvironment) and treatment efficacy. This study intends to explore the clinical value of PD-1/IL-2 bispecific antibody in the neoadjuvant setting for recurrent resectable HCC, and provide evidence for its clinical application in this patient population.

Key facts

Study ID

NCT07644208

Run by

Shanghai Zhongshan Hospital

People needed

30

Starts

2026-06-15

Expected to finish

2029-04-01

Last updated by the study team

2026-06-12

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Have signed the written informed consent form and be able to comply with all scheduled visits and study procedures specified in the protocol.
• Aged between 18 and 75 years old (inclusive), with no restriction on gender.
• Diagnosed with hepatocellular carcinoma (HCC) confirmed by histopathology or cytology, or meeting the clinical diagnostic criteria for HCC formulated by the American Association for the Study of Liver Diseases (AASLD) or the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer.
• Must provide tumor tissue specimens obtained from the initial surgical resection during the screening period.
• Have a history of curative hepatectomy for HCC, with pathologically confirmed tumor recurrence occurring 3 months to 2 years after surgery. Candidates shall be assessed by a multidisciplinary team (MDT) and meet all the following criteria for repeat resection:
• CNLC stage Ia-Ib or IIa-IIb, with recurrent lesions confined to one hepatic lobe; Adequate liver function reserve with Child-Pugh Class A; The volume of the future liver remnant (FLR) accounts for ≥40% of the standard liver volume (SLV) in patients with chronic liver disease, liver parenchymal damage or liver cirrhosis, or ≥30% in patients without liver fibrosis or cirrhosis; No vascular tumor thrombus; No extrahepatic metastasis.
• Have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), and the lesion has not received any local therapy.
• Have adequate organ and bone marrow function. Laboratory test results obtained within 7 days prior to enrollment shall meet the following requirements. No blood products, erythropoietin, colony-stimulating factors, thrombopoietin, albumin or other parenteral corrective medications are allowed within 14 days before laboratory testing:
• Hematology: Hemoglobin (HGB) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; Platelet (PLT) count ≥ 100×10⁹/L.
• Liver function: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN). Participants with TBIL > 1.5 × ULN but conjugated bilirubin ≤ ULN are also eligible; Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 5 × ULN; Alkaline Phosphatase (ALP) ≤ 4 × ULN; Serum albumin ≥ 30 g/L.
• Renal function: Serum Creatinine (Cr) ≤ 1.5 × ULN, or Creatinine Clearance (CCr) ≥ 50 mL/min (calculated by the Cockcroft-Gault formula using actual body weight). Urinalysis shows urine protein < 2+. For participants with urine protein ≥ 2+ at baseline, the 24-hour urinary protein quantification shall be < 1 g.
• Coagulation function: International Normalized Ratio (INR) ≤ 1.5 × ULN; Partial Thromboplastin Time (PTT) / Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN. Participants on stable-dose anticoagulant therapy shall remain within the expected therapeutic range of the prescribed anticoagulants.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Expected survival time of no less than 6 months.
• Female participants of childbearing potential and male participants whose partners are of childbearing potential must agree to use effective contraception throughout the treatment period and for 6 months after the last study drug administration.

You may not qualify if…

• Histologically or cytologically confirmed diagnosis of tumors containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, mixed carcinoma, and intrahepatic cholangiocarcinoma.
• Prior treatment with anti-PD-1/PD-L1 agents or other antitumor immunotherapies.
• Presence of unresolved Grade >1 toxicities related to any previous antitumor therapy (persistent Grade 2 alopecia, anemia, peripheral neuropathy, electrolyte abnormalities manageable with treatment, and endocrine disorders well-controlled with hormone replacement therapy are excluded).
• History of hepatic encephalopathy or seizures; presence of active, newly diagnosed or untreated central nervous system metastases, spinal cord compression, carcinomatous meningitis or leptomeningeal metastases.
• Presence of clinically significant cardiovascular and cerebrovascular diseases, including:
• Severe conduction disorders (e.g., third-degree atrioventricular block);
• Symptomatic, clinically unstable arrhythmias or arrhythmias requiring clinical intervention;
• Corrected QT interval (QTc, calculated via Fridericia's formula) ≥ 480 ms;
• Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >90 mmHg despite optimal medical treatment), or history of hypertensive crisis or hypertensive encephalopathy;
• History of myocarditis;
• Symptomatic congestive heart failure (New York Heart Association Class II-IV) or left ventricular ejection fraction (LVEF) < 50% on cardiac ultrasonography;
• Any arterial thrombosis, embolism or ischemic event within 6 months prior to the first study drug administration, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack;
• History of deep vein thrombosis, pulmonary embolism or other severe thromboembolic events within 6 months before enrollment (Thrombosis related to implantable venous access ports, catheters or superficial phlebitis is not defined as severe thromboembolism). Patients with adequately treated deep vein thrombosis may be enrolled if deemed stable by the investigator.
• Current or prior history of interstitial pneumonia, pulmonary fibrosis, pneumoconiosis, drug-induced pneumonitis, radiation pneumonitis, severe pulmonary dysfunction or other restrictive lung diseases requiring corticosteroids or other treatments.
• History of severe or uncontrolled allergic diathesis, drug allergy, asthma or atopic dermatitis.
• Known allergy to IL-2, sintilimab, other monoclonal antibodies or their excipients.
• Symptomatic pleural effusion, ascites or pericardial effusion requiring repeated drainage (Patients with effusions not requiring drainage or with no obvious reaccumulation within 3 days after drainage discontinuation are eligible for enrollment).
• History of active autoimmune diseases requiring systemic therapy (e.g., disease-modifying drugs, corticosteroids or immunosuppressants) within 2 years prior to the first drug administration. Replacement therapies (e.g., levothyroxine, insulin, physiological corticosteroids for adrenal or pituitary insufficiency) are not regarded as systemic treatment.
• History of allogeneic organ transplantation (including liver transplantation) or allogeneic hematopoietic stem cell transplantation.
• Active uncontrolled bleeding, known bleeding diathesis, unhealed severe wounds, ulcers or fractures; history of esophagogastric variceal bleeding caused by portal hypertension within the preceding 6 months. Grade 3 varices confirmed by endoscopy within 3 months before the first administration. Patients with evidence of portal hypertension (including splenomegaly on imaging) with high bleeding risk assessed by investigators shall undergo endoscopic evaluation.
• Presence of major gastrointestinal diseases within 6 months prior to or at the time of drug administration, including gastrointestinal perforation, severe gastrointestinal fistula (with severely impaired gastrointestinal function or requiring invasive intervention), history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated with chronic diarrhea), Crohn's disease, ulcerative colitis or long-standing chronic diarrhea.
• Confirmed HIV positivity or history of acquired immunodeficiency syndrome (AIDS); active hepatitis B or hepatitis C (HCV), or history of infection with the above viruses.
• For patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), HBV DNA testing is required. Those with HBV DNA ≤ 10⁴ copies/mL, ≤ 2000 IU/mL or below the lower limit of quantification are eligible. HBsAg-positive patients must receive antiviral therapy throughout the study with regular HBV DNA monitoring.
• Patients with positive HCV serology but undetectable HCV RNA are permitted to enroll.
• Patients who have completed anti-HCV treatment with undetectable viral load are eligible for enrollment.

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.