Combining Tislelizumab with TACE and Lenvatinib for Treating Resectable Liver Cancer

A Single-arm Exploratory Clinical Study of Tislelizumab Combined With Transarterial Chemoembolization (TACE) and Lenvatinib in the Neoadjuvant Treatment of Resectable CNLC Stage Ⅱa-Ⅱb Hepatocellular Carcinoma

This study is testing a new combination treatment of tislelizumab, TACE, and lenvatinib to see if it can help people with early-stage liver cancer have better surgery outcomes and reduce the chances of cancer coming back.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Fujian Medical University (Academic / other)
• Drugs / interventions: Tislelizumab, Lenvatinib, immunotherapy, radiation, chemotherapy
• Locations: 1 site (Fuzhou, Fujian)
• Trial ID: NCT06003673 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the effectiveness and safety of a combination therapy involving tislelizumab, transarterial chemoembolization (TACE), and lenvatinib as neoadjuvant treatment for patients with resectable hepatocellular carcinoma (HCC) at CNLC stage IIa-IIb. The study is a single-arm, prospective trial that aims to improve the R0 resection rate, reduce distant metastasis, and lower postoperative recurrence rates. A total of 20 patients will undergo two cycles of this neoadjuvant therapy before surgical resection, with the primary endpoint being recurrence-free survival (RFS).

Who should consider this trial

Good fit: Ideal candidates are Chinese patients aged 18 to 75 with histologically confirmed resectable hepatocellular carcinoma at CNLC stage IIa-IIb.

Not a fit: Patients with advanced liver disease, prior systemic treatment, or those not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve surgical outcomes and long-term survival rates for patients with resectable HCC.

How similar studies have performed: While there is limited research on neoadjuvant therapy for HCC, similar approaches in other cancers have shown promising results, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Participants must voluntarily enroll in this study and provide signed informed consent.
2. Male or female patients between the ages of 18 and 75 years old.
3. Patients diagnosed with hepatocellular carcinoma (HCC) confirmed by histopathology or imaging.
4. Chinese liver cancer staging of IIa-IIb with hepatocellular carcinoma considered resectable by the investigator. For IIa-stage patients, they must meet at least one of the following criteria: unclear tumor margins, proximity to blood vessels, or suspicious residual margins.
5. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) guidelines (measurable lesions with CT scan long diameter ≥ 10 mm or lymph node lesions with CT scan short diameter ≥ 15 mm, and no prior local treatment such as radiation or cryotherapy).
6. Child-Pugh liver function class A.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. No prior systemic treatment for HCC.
9. For HBsAg-positive patients, HBV-DNA \< 200,000 IU/ml (106 copies/ml), and receiving routine antiviral therapy.
10. Expected survival of at least 3 months.
11. Normal major organ function, meeting the following criteria:

    * Hematology criteria:
    * Hemoglobin (HB) ≥ 90 g/L;
    * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/m3);
    * Platelet count (PLT) ≥ 75 × 109/L.
    * Biochemistry criteria:
    * Total bilirubin (TBIL) ≤ 2 × ULN;
    * ALT, ALP, and AST ≤ 5 × ULN;
    * Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 50 ml/min (calculated using the Cockcroft-Gault formula: CrCL (mL/min) = \[(140 - age) × body weight (kg) × F\] / (SCr(mg/dL) × 72). Where F=1 for males and F=0.85 for females; SCr=serum creatinine).
    * Coagulation function: International Normalized Ratio (INR) ≤ 2.3.
12. Blood pressure (BP) controlled with a maximum of 3 antihypertensive medications, defined as BP ≤ 150/90 mmHg at screening, and no changes in antihypertensive treatment within one week before Cycle 1/Day 1.
13. Doppler echocardiography: Left Ventricular Ejection Fraction (LVEF) ≥ lower limit of normal (50%).
14. Women of childbearing potential must use reliable contraceptive methods or undergo pregnancy testing (serum or urine) within 7 days before enrollment, with negative results, and agree to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of investigational drugs. For males, they must agree to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of investigational drugs or have undergone surgical sterilization.

Exclusion Criteria:

1. Extrahepatic metastasis of primary liver cancer.
2. Diffuse liver cancer with tumor burden ≥ 50% of liver volume; and/or macrovascular invasion of the portal vein classified as Type IV; and/or inferior vena cava tumor thrombosis.
3. Prior treatment with targeted immunotherapy agents, including but not limited to anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibodies.
4. Contraindications for Transarterial Chemoembolization (TACE) treatment.
5. Participation in other investigational drug trials within the past 4 weeks.
6. Medical history and comorbidities:1)Active, known, or suspected autoimmune diseases, including a history of allogeneic organ transplantation, allogeneic hematopoietic stem cell transplantation, HIV positive history, or acquired immunodeficiency syndrome (AIDS) history. 2)Severe cardiovascular diseases: Grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia; NYHA Class III-IV heart failure, or left ventricular ejection fraction (LVEF) \< 50% based on echocardiography. 3)Active infections. 4)Known allergies to components of Tislelizumab or Lenvatinib. 5)History of substance abuse, alcoholism, or drug addiction.
7. Ineligibility as determined by the investigator.

Where this trial is running

Fuzhou, Fujian

• The First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China (Recruiting)

Study contacts

• Principal investigator: Zhang Zhibo, PhD — First Affiliated Hospital of Fujian Medical University
• Study coordinator: Zhang Zhibo, PhD

Conditions Hepatocellular Carcinoma Resectable; hepatocellular carcinoma; resectable; CNLC stage IIa-IIb; neoadjuvant therapy; Tislelizumab; Lenvatinib; Transarterial Chemoembolization