A Study to Evaluate TACE Sequential Tislelizumab as Adjuvant Therapy in Participants With HCC at High Risk of Recurrence After Curative Resection

Study Overview
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Brief Summary
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This is an open label, multi-center, phaseⅡstudy to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in hepatocellular carcinoma (HCC) patients who are at high risk of recurrence after curative resection.

Detailed Description
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Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Surgical resection is the most important radical treatment. However, the recurrence rate is high especially in the patients with high risk of recurrence after curative resection. How to reduce postoperative recurrence and improve survival is currently a direction that is worth exploring. Until now there is no standard postoperative adjuvant therapy. Previous studies have shown that TACE combined with PD-1 inhibitors has a synergistic enhancement effect, and this study is to explore the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in HCC patients who are at high risk of recurrence after curative resection.

Official Title
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Official Title ICMJE A Phase 2, Open-Label, Multi-Center, Single Arm Study to Evaluate the Efficacy and Safety of TACE Sequential Tislelizumab as Adjuvant Therapy in Participants With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection

Conditions
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Hepatocellular Carcinoma, Adjuvant Therapy

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a histopathological or cytologically diagnosis of HCC Subjects who have undergone a curative resection High risk for HCC recurrence as protocol defined No previous systematic treatment and locoregional therapy for HCC Child-Pugh Score, Class A ECOG performance status 0 or 1 Full recovery from surgical resection Adequate organ function Absence of major macrovascular invasion No extrahepatic spread Life expectancy of at least 6 months Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC Evidence of residual, recurrent, or metastatic disease Known history of serious allergy to any monoclonal antibody History of hepatic encephalopathy Tumor thrombus in portal vein or superior mesenteric vein or inferior caval vein Portal hypertension with bleeding esophageal or gastric varices within 6 months prior to initiation of treatment Any bleeding or thrombotic disorder within 6 months prior to initiation of treatment Any active malignancy within 2 years prior to the start of treatment Active or history of autoimmune disease Other acute or chronic conditions, psychiatric disorders, or laboratory abnormalities that may increase the risk of study participation Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or other immunotherapy Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Postoperative TACE + Tislelizumab 200mg IV Q3W<br>TACE will be performed after curative resection (4±1w) once and then Tislelizumab Injection will be initiated after TACE (5±2d). Tislelizumab will be administered every three weeks, until the disease recurrence, intolerable toxicity, death, withdrawal of consent or completion of 17 cycles of Tislelizumab. | Drug: Tislelizumab<br>* Tislelizumab 200mg IV Q3W<br>* Other names: Anti-PD-1 therapy;Drug: TACE<br>* TACE will be performed after curative resection (4±1w)<br>* Other names: Transarterial Chemoembolization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Recurrence Free Survival Rate (2-year RFS rate) | 2-year RFS rate is defined as the proportion of patients alive and free of recurrence at 2 years after curative resection. | Observation period 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-Free Survival (RFS) | RFS is defined as the time from the date of curative resection to the first documented recurrence or death due to any cause, whichever occurs first. | 24 months | 
| Time to recurrence (TTR) | TTR is defined as the time from the date of curative resection to the first documented recurrence. | 24 months | 
| Overall Survival (OS） | OS is defined as the time from the date of curative resection until death due to any cause. | 24 months | 
| 1-year RFS rate | 1-year RFS rate is defined as the proportion of patients alive and free of recurrence at 1 years after curative resection. | 12 months | 
| 1-year OS rate/2-year OS rate | OS rate is defined as the proportion of patients who have not experienced death from any cause at 12 and 24 months after curative resection. | 12 months/24 months | 
| Adverse Events (AEs) | The grade of AEs and the number of patients with AEs are assessed based on CTCAE v5.0 | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Immunotherapy, Transarterial chemoembolization, Recurrence, Antineoplastic Agents, Immunological, Antineoplastic Agents