Adjuvant Tislelizumab Plus Lenvatinib for Patients at High-risk of HCC Recurrence After Curative Resection or Ablation

Study Overview
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Brief Summary
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Though hepatic resection and ablation are the curative treatments for patients with hepatocellular carcinoma (HCC), the 5-years recurrence-free survival is lower than 30%. In recent years, several immune checkpoint inhibitors have been approved in advanced or unresectable HCC. No study about the safety and efficacy of adjuvant immune checkpoint inhibitors for patients with HCC after hepatectomy is reported.

Detailed Description
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Hepatic resection and ablation are the best treatments for patients with early stage hepatocellular carcinoma (HCC) or selected intermediate or advanced disease. However, the postoperative 5-years recurrent rate is up to 70%, for whom recurrence is a major cause of death. In recent years, several immune checkpoint inhibitors have been approved in advanced HCC by official guidelines. At the same time, four randomizead controlled trials about adjvuant immune checkpoint inhibitors for postoperative HCC are ongoing. A prospective cohort study found adjuvant immune checkpoint inhibitors with or without tyrosine kinase inhibitors may improve recurrence-free survival of patients at high-risk of HCC recurrence after curative resection (DOI: 10.1200/JCO.2023.41.16_suppl.4119. Journal of Clinical Oncology 41, no. 16_suppl. 4119). Therefore, the investigators plan to compare the safety and efficacy of adjuvant Tislelizumab plus lenvatinib to Tislelizumab monotherapy for patients with high-risk factor of HCC recurrence after curative resection and ablation in a multicentric, prospective study.

Official Title
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Adjuvant Tislelizumab With or Without Lenvatinib for Patients at High-risk of Hepatocellular Carcinoma Recurrence After Curative Resection or Ablation: a Multicentric, Prospective Study

Conditions
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Hepatocellular Carcinoma, Recurrence, Immune Checkpoint Inhibitor

Intervention / Treatment
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* Drug: Adjuvant tislelizumab plus lenvatinib
* Drug: Adjuvant tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 75 years (inclusive); Diagnosis of HCC confirmed by postoperative histopathology; Underwent curative resection, as defined based on intra- and postoperative criteria; With high-risk factors of recurrence after curative treatment, based on preoperative radiological imaging or pathology reports indicating a tumor at least 5 cm in diameter, micro- or macrovascular invasion (Vp1/Vp2), satellite or multinodular tumors, and/or Grade 3/4 pathology; No residual cancer detected by radiological imaging in the liver within 8 weeks after curative resection; Child-Pugh 5-7 scores liver function; Eastern Cooperative Oncology Group performance status of 0 or 1. Exclusion Criteria: Received neoadjuvant immune checkpoint inhibitors or tyrosine kinase inhibitors before resection or ablation; A history of other malignancies; History of active autoimmune or immunodeficiency diseases; Concurrent cardiac, pulmonary, cerebral, or renal dysfunction; Loss to follow-up within six months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant tislelizumab plus lenvatinib<br>Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab plus lenvatinib treatment for six months, HCC recurrence, or unacceptable adverse events. | Drug: Adjuvant tislelizumab plus lenvatinib<br>* Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab plus lenvatinib treatment for six months, HCC recurrence, or unacceptable adverse events.<br>|
| Active Comparator: Adjuvant tislelizumab<br>Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab treatment for six months, HCC recurrence, or unacceptable adverse events. | Drug: Adjuvant tislelizumab<br>* Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab treatment for six months, HCC recurrence, or unacceptable adverse events.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrene-free survival | Recurrene-free survival will be calculated using the Kaplan-Meier method, and differences between groups are assessed for significance using the log-rank test. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival will be calculated using the Kaplan-Meier method, and differences between groups are assessed for significance using the log-rank test. | 3 years | 
| Adverse events | Adverse events are expressed as number and percentage. | 1 years |