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

NCT07644208 | Not Yet Recruiting Phase 2

• 1 other identifier: NEOHCC-BSP
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Hepatocellular Carcinoma; Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response Rate (MPR)

  Major Pathological Response (MPR) is defined as the proportion of patients with ≤50% residual viable tumor cells in the resected specimen after neoadjuvant treatment,

  24 months

Secondary Outcomes (7)

• Complete Pathological Response Rate (pCR)

  24 months

• Event-Free Survival (EFS)

  From first dose to up to 2 years after surgery

• Overall Survival (OS)

  From first dose to up to 5 years after surgery

• R0 Resection Rate

  At the time of surgical resection, approximately 7-11 weeks after the first dose of neoadjuvant treatment

• Objective Response Rate (ORR)

  From first dose to pre-surgical tumor assessment, approximately 7-11 weeks after the first dose of neoadjuvant treatment

Other Outcomes (1)

• Correlation Between Biomarkers and Treatment Efficacy

  At baseline and at the time of surgical resection, approximately 7-11 weeks after the first dose of neoadjuvant treatment

Study Arms (1)

PD-1/IL-2 Bispecific Antibody Fusion Protein Neoadjuvant Therapy

EXPERIMENTAL

Patients will receive neoadjuvant treatment with a PD-1/IL-2 Bispecific Antibody Fusion Protein administered by intravenous infusion for 3 cycles prior to surgery. Patients who remain eligible after completing neoadjuvant treatment will undergo curative surgical resection, followed by pathological response assessment and long-term follow-up for survival and disease recurrence.

Biological: PD-1/IL-2 Bispecific Antibody Fusion Protein

Interventions

PD-1/IL-2 Bispecific Antibody Fusion Protein BIOLOGICAL

A recombinant PD-1/IL-2 bispecific antibody fusion protein that simultaneously blocks the PD-1/PD-L1 pathway and activates the IL-2 signaling pathway. It is administered by intravenous infusion as neoadjuvant therapy prior to curative surgical resection. Patients receive multiple cycles of treatment, starting with a lower priming dose followed by standard doses administered every 2 weeks. After completing neoadjuvant treatment, eligible patients proceed to curative hepatectomy followed by long-term follow-up.

PD-1/IL-2 Bispecific Antibody Fusion Protein Neoadjuvant Therapy

Eligibility Criteria

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

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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

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

• Jian Zhou

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

XiaoYong Huang

CONTACT

+8615021519215; huang.xiaoyong@zs-hospital.sh.cn

Yue Zhang

CONTACT

+86 13209590212; zyue4283@gamil.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: Professor

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share