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
Trial Snapshot
- Phase
- Phase 3
- Status
- Withdrawn
- Sponsor
- Primary Endpoint
- Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
Treatment Arm A: sitravatinib + tislelizumab
sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: Sitravatinib (Drug)
Treatment Arm A: sitravatinib + tislelizumab
sitravatinib once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: Tislelizumab (Drug)
Treatment Arm B: Placebo + tislelizumab
sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: Tislelizumab (Drug)
Treatment Arm B: Placebo + tislelizumab
sitravatinib-matching placebo once daily and tislelizumab once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: sitravatinib-matching placebo (Drug)
Treatment Arm C:Sitravatinib + Placebo
sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: Sitravatinib (Drug)
Treatment Arm C:Sitravatinib + Placebo
sitravatinib once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: tislelizumab-matching placebo (Drug)
Treatment Arm D: Matching Placebo
sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: sitravatinib-matching placebo (Drug)
Treatment Arm D: Matching Placebo
sitravatinib-matching placebo once daily and tislelizumab-matching placebo once every 6 weeks, for up to 17 cycles (approximately 2 years)
Intervention: tislelizumab-matching placebo (Drug)
Outcomes
Primary Outcomes
Recurrence-free survival (RFS) as assessed by the investigator between Arm B and Arm D
Time Frame: 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
Time Frame: 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 Outcomes
- Arm A and Arm D: overall survival (OS)(Up to 5 Years)
- Arm A and Arm B: overall survival (OS)(Up to 5 Years)
- Arm A and Arm C: time to extrahepatic spread (EHS) as assessed by the investigator(Up to 2 Years)
- Number of participants with adverse events (AEs)(Up to 5 Years)
- Arm A and Arm B: time to extrahepatic spread (EHS) as assessed by the investigator(Up to 2 Years)
- Arm A and Arm C: overall survival (OS)(Up to 5 Years)
- Arm A and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator(Up to 2 Years)
- Arm B and Arm D: time to extrahepatic spread (EHS) as assessed by the investigator(Up to 2 Years)
- Arm A and Arm C: Recurrence-free survival (RFS)(Up to 2 Years)
- Arm A and Arm B: Recurrence-free survival (RFS)(Up to 2 Years)
- Arm B and Arm D: overall survival (OS)(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(Up to 2 Years)