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

Phase 3

Withdrawn

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: Tislelizumab; Drug: sitravatinib-matching placebo; Drug: Sitravatinib; Drug: tislelizumab-matching placebo

• Registration Number: NCT05564338
• Lead Sponsor: BeiGene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-29
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-03
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-06
• Last Update Posted: 2023-06-07
• Study Start: 2023-06-30
• Primary Completion: 2027-04-30
• Study Completion: 2028-04-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. 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
2. Participant must have tumor-free status as assessed by the investigator and have fully recovered from surgical resection before randomization
3. Participant must have no extrahepatic HCC
4. ECOG Performance Status ≤ 1
5. Participant who has undergone surgical resection and is defined as having a high risk of HCC recurrence

Key

Exclusion Criteria

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
2. Evidence of residual, recurrent, or metastatic disease of HCC before randomization
3. 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
4. Untreated chronic hepatitis B (HBV) or chronic HBV carriers with HBV DNA ≥ 2000 IU/mL at Screening
5. Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm B: Placebo + tislelizumab	Tislelizumab	sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm D: Matching Placebo	sitravatinib-matching placebo	sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm C:Sitravatinib + Placebo	tislelizumab-matching placebo	sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm D: Matching Placebo	tislelizumab-matching placebo	sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm B: Placebo + tislelizumab	sitravatinib-matching placebo	sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm A: sitravatinib + tislelizumab	Sitravatinib	sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm A: sitravatinib + tislelizumab	Tislelizumab	sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Treatment Arm C:Sitravatinib + Placebo	Sitravatinib	sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)

Primary Outcome Measures

Name	Time	Method
Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D	Up to 2 Years	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.
Recurrence-free survival (RFS) as assessed by the investigator between Arm A and Arm D	Up to 2 Years	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.

Secondary Outcome Measures

Name	Time	Method
Arm A and Arm D: overall survival (OS)	Up to 5 Years	defined as the time from the date of randomization until the date of death due to any cause
Arm A and Arm B: overall survival (OS)	Up to 5 Years	defined as the time from the date of randomization until the date of death due to any cause
Arm A and Arm C: time to extrahepatic spread (EHS) as assessed by the investigator	Up to 2 Years	defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Number of participants with adverse events (AEs)	Up to 5 Years	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
Arm A and Arm B: time to extrahepatic spread (EHS) as assessed by the investigator	Up to 2 Years	defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Arm A and Arm C: overall survival (OS)	Up to 5 Years	defined as the time from the date of randomization until the date of death due to any cause
Arm A and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator	Up to 2 Years	defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Arm B and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator	Up to 2 Years	defined as the time from the date of randomization until the date of the first documented occurrence of extrahepatic HCC
Arm A and Arm C: Recurrence-free survival (RFS)	Up to 2 Years	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.
Arm A and Arm B: Recurrence-free survival (RFS)	Up to 2 Years	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.
Arm B and Arm D: overall survival (OS)	Up to 5 Years	defined as the time from the date of randomization until the date of death due to any cause
Participants Reported Outcome as measured at Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and its hepatocellular carcinoma cancer module QLQ-HCC18	Up to 2 Years	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