Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Participants With Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of sitravatinib plus tislelizumab or placebo plus tislelizumab versus placebo. The study will also compare the recurrence-free survival (RFS) in participants with hepatocellular carcinoma (HCC) who are at high risk of recurrence after surgical resection.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Compare the Efficacy and Safety of Sitravatinib Plus Tislelizumab or Placebo Plus Tislelizumab Versus Placebo as Adjuvant Treatment in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Surgical Resection

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Sitravatinib
* Drug: Tislelizumab
* Drug: sitravatinib-matching placebo
* Drug: tislelizumab-matching placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant with a first diagnosis of HCC must have undergone a curative-intent resection within 4 to 12 weeks before randomization and have a documented histological confirmation of HCC diagnosis and negative surgical margins (R0 resection) of the resected tumor Participant must have tumor-free status as assessed by the investigator and have fully recovered from surgical resection before randomization Participant must have no extrahepatic HCC ECOG Performance Status ≤ 1 Participant who has undergone surgical resection and is defined as having a high risk of HCC recurrence Key Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology Evidence of residual, recurrent, or metastatic disease of HCC before randomization Major macrovascular (gross vascular) invasion of the portal vein (Vp3 or Vp4) or any grade of macrovascular invasion in the hepatic vein or inferior vena cava Untreated chronic hepatitis B (HBV) or chronic HBV carriers with HBV DNA ≥ 2000 IU/mL at Screening Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding Note: Other protocol defined Inclusion/Exclusion criteria may apply

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A: sitravatinib + tislelizumab<br>sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years) | Drug: Sitravatinib<br>* Administered orally<br>Drug: Tislelizumab<br>* Administered intravenously<br>|
| Experimental: Treatment Arm B: Placebo + tislelizumab<br>sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years) | Drug: Tislelizumab<br>* Administered intravenously<br>Drug: sitravatinib-matching placebo<br>* administered orally<br>|
| Experimental: Treatment Arm C:Sitravatinib + Placebo<br>sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years) | Drug: Sitravatinib<br>* Administered orally<br>Drug: tislelizumab-matching placebo<br>* administered intravenously<br>|
| Experimental: Treatment Arm D: Matching Placebo<br>sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years) | Drug: sitravatinib-matching placebo<br>* administered orally<br>Drug: tislelizumab-matching placebo<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival (RFS) as assessed by the investigator between Arm A and Arm D | RFS is defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma (HCC) as assessed by the investigator, or death from any cause, whichever occurs first. | Up to 2 Years | 
| Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D | defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first. | Up to 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm A and Arm B: Recurrence-free survival (RFS) | defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first. | Up to 2 Years | 
| Arm A and Arm C: Recurrence-free survival (RFS) | defined as the time from the date of randomization until the date of the first documented occurrence of intrahepatic or extrahepatic hepatocellular carcinoma as assessed by the investigator, or death from any cause, whichever occurs first. | Up to 2 Years | 
| Arm A and Arm D: overall survival (OS) | defined as the time from the date of randomization until the date of death due to any cause | Up to 5 Years | 
| Arm B and Arm D: overall survival (OS) | defined as the time from the date of randomization until the date of death due to any cause | Up to 5 Years | 
| Arm A and Arm B: overall survival (OS) | defined as the time from the date of randomization until the date of death due to any cause | Up to 5 Years | 
| Arm A and Arm C: overall survival (OS) | defined as the time from the date of randomization until the date of death due to any cause | Up to 5 Years | 
| Arm A and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator | defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC | Up to 2 Years | 
| Arm B and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator | defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC | Up to 2 Years | 
| Arm A and Arm B: time to extrahepatic spread (EHS) as assessed by the investigator | defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC | Up to 2 Years | 
| Arm A and Arm C: time to extrahepatic spread (EHS) as assessed by the investigator | defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC | Up to 2 Years | 
| Number of participants with adverse events (AEs) | Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0, vital signs, and clinical laboratory test results in the Safety Analysis Set | Up to 5 Years | 
| Participants Reported Outcome as measured at Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and its hepatocellular carcinoma cancer module QLQ-HCC18 | Quality of Life change with treatment. Scale scores are calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100 | Up to 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, sitravatinib, tislelizumab