A Study of Neoadjuvant Tislelizumab Plus Lenvatinib in Resectable HCC at High Risk of Recurrence

NCT07475026 | Not Yet Recruiting Phase 3

• 1 other identifier: 2512012685
• Study Type: interventional
• Target: 198
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, randomized controlled, phase 3 study to explore the efficacy and safety of neoadjuvant tislelizumab plus lenvatinib in patients with resectable HCC at high risk of recurrence.

Conditions

HCC - Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 1-year event-free survival rate

  1 year after randomization

Secondary Outcomes (10)

• Objective response rate

  6 weeks after randomization

• Disease control rate

  6 weeks after randomization

• Major pathologic response rate

  10 weeks after randomization

• 1-year recurrence-free survival rate

  1 year after randomization

• 2-year recurrence-free survival rate

  2 year after randomization

Other Outcomes (1)

• Response prediction accuracy (AUC-ROC)

  36 months after randomization

Study Arms (2)

Arm A

NO INTERVENTION

The Surgery-alone Group: the patients will receive surgery alone after enrollment and randomization.

Arm B

EXPERIMENTAL

The Neoadjuvant Treatment Group: the patients will receive 2 cycles of neoadjuvant tislelizumab plus lenvatinib after enrollment and randomization and receive surgery in sequence.

Drug: Tislelizumab; Drug: Lenvatinib

Interventions

Tislelizumab DRUG

Tislelizumab, 200mg, IV, q3w. Treatment will be given in 3-week cycles for a total of 2 cycles.

Arm B

Lenvatinib DRUG

Lenvatinib, 8mg for BW\<60kg or 12mg for BW≥60kg, PO, qd. Treatment will be given in 3-week cycles for a total of 2 cycles.

Arm B

Eligibility Criteria

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

You may qualify if:

• Voluntarily participates in this study and provides written informed consent.
• Aged 18 to 75 years, inclusive; male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Child-Pugh class A liver function.
• China Liver Cancer (CNLC) stage Ib to IIa.
• Histologically/cytologically confirmed HCC, or clinically diagnosed primary hepatocellular carcinoma according to accepted diagnostic criteria, with lesions meeting the criteria for surgical resection as defined in the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 edition).
• At least one measurable lesion per RECIST v1.1.
• Estimated life expectancy ≥ 6 months.
• Adequate major organ function as defined below, without transfusion of any blood components or use of hematopoietic growth factors within 14 days prior to assessment:
• Hematology
• Absolute neutrophil count (ANC) ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 5.6 mmol/L (9 g/dL)
• Hepatic and renal function
• Serum creatinine (SCr) ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula)

You may not qualify if:

• Prior antitumor therapy for the current HCC, including radiotherapy, chemotherapy, concurrent chemoradiotherapy, other locoregional therapies (e.g., TACE, HAIC), or prior immunotherapy or targeted therapy.
• Note: Patients who developed recurrence after prior surgery may be enrolled; if prior postoperative adjuvant therapy was given, enrollment is allowed only if ≥6 months have elapsed since completion of adjuvant therapy.
• Known cholangiocarcinoma, sarcomatoid HCC, mixed hepatocellular-cholangiocarcinoma, or fibrolamellar carcinoma; or any other active malignancy besides HCC within the past 5 years or concurrently (except cured basal cell carcinoma of the skin and cervical carcinoma in situ).
• Hypertension inadequately controlled with antihypertensive therapy (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg); or history of hypertensive crisis or hypertensive encephalopathy.
• Known hypersensitivity to macromolecular protein preparations, or known allergy to tislelizumab, lenvatinib, or any of their excipients.
• Any active autoimmune disease or history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis/colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Patients with vitiligo, or asthma that completely resolved in childhood and requires no intervention in adulthood, may be eligible. Patients with asthma requiring medical intervention with bronchodilators are not eligible.
• Use of immunosuppressive agents or systemic, or absorbable topical, corticosteroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment.
• Symptomatic ascites or pleural effusion requiring therapeutic paracentesis or drainage.
• Uncontrolled clinically significant cardiac symptoms or disease, including any of the following:
• New York Heart Association (NYHA) class \> II heart failure
• Unstable angina
• Myocardial infarction within 1 year
• Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention
• Within the past 3 months, presence of gastrointestinal conditions such as esophageal varices, active gastric or duodenal ulcer, ulcerative colitis, portal hypertension, or active bleeding from an unresected tumor; or any other condition judged by the investigator to confer a risk of gastrointestinal bleeding or perforation.
• History of or current severe bleeding (within 3 months, bleeding volume \>30 mL), hemoptysis (within 4 weeks, \>5 mL fresh blood), or thromboembolic events within 12 months (including stroke and/or transient ischemic attack).

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab; lenvatinib

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 Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 16, 2026
• Study Start: May 30, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share