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

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

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 Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: Sitravatinib; Drug: sitravatinib-matching placebo; Drug: tislelizumab-matching placebo

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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 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
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
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
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

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; tislelizumab; sitravatinib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: BGB-A317-Sitravatinib-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No