A Clinical Study to Compare the Efficacy and Safety of HLX10 in Combination With HLX04 Versus Sorafenib as the First-line Treatment in Patients With Locally Advanced or Metastatic HCC

A Randomized, Open-Label, Controlled, Multicenter, Phase III Clinical Study to Compare the Efficacy and Safety of HLX10 (Anti-PD-1 Antibody) in Combination With HLX04 (Anti-VEGF Antibody) Versus Sorafenib as the First-line Treatment in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC)

This study is a randomized, double-blind, multicenter, phase III clinical study to compare the efficacy and safety of HLX10 + HLX04 vs Sorafenibas as the First-line Treatment in Patients with Locally Advanced or Metastatic HCC

Eligible subjects in this study will be randomized to Arm A or Arm B at 2:1 ratio as follows:

Arm A (treatment group): HLX10 + HLX04 Arm B (control group): sorafenib Randomization is stratified by: region (Asia (excluding Japan) vs. others), HBV infection vs. HCV infection vs. no HBV or HCV infection, portal vein invasion or/and extrahepatic spread (with vs.without), and ECOG (0 vs. 1).

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: HLX10; Drug: HLX04; Drug: Sorafenib

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Ethics committee of zhongshan hospital affiliated to fudan university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Volunteer to participate in the clinical study;
2. Aged ≥ 18 years and ≤ 75 years;
3. Patients with histopathologically or cytologically diagnosed locally advanced or metastatic and/or unresectable HCC , or patients with clinically diagnosed HCC according to the diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD);
4. Barcelona Clinic Liver Cancer (BCLC) Stage C; or BCLC Stage B patients who are not candidates for radical surgery and/or locoregional therapy.
5. Received no prior systemic HCC treatment (including chemotherapy, treatment with sorafenib, regorafenib, lenvatinib, or other small-molecule antiangiogenic agents);
6. At least one measurable lesion by the IRRC (central radiography) as per RECIST v1.1
7. Normal major organ functions as defined

Exclusion Criteria:

1. Patients with known hepatobiliary cell carcinoma, mixed cell carcinoma, or fibrolamellar cell carcinoma;
2. History of hepatic encephalopathy;
3. Patients with portal hypertension complicated with upper gastrointestinal hemorrhage, or esophageal/gastric fundal varices with the red color sign, or high hemorrhage risk investigated by the investigator within 6 months before the randomization. Subjects must receive endoscopic examinations to rule out high hemorrhage risk (e.g. red color sign and severe varices) before enrollment.
4. Patients with portal vein invasion at the main portal branch (Vp4), inferior vena cava involvement, or right cardiac involvement of HCC based on imaging examination. Patients with portal vein invasion at the main portal branch but with unobstructed blood flow in the bilateral or unilateral branch can be enrolled;
5. Central nervous system (CNS) or leptomeningeal metastases;
6. Positive for both HBV-DNA and HCV-RNA;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (treatment group); HLX10 in combination with HLX04	Drug: HLX10; HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.; Drug: HLX04; HLX04 is an recombinant anti-VEGF humanized monoclonal antibody ，developed by Shanghai Henlius Biotech, Inc.; Other Names: HLX04 ( anti-VEGF antibody )
Sham Comparator: B (control group); sorafenib	Drug: Sorafenib; Sorafenib is a multi-target, multi-kinase inhibitor capable.The standard treatment of HCC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor assessment	Overall survival (OS): defined as a period from randomization to death of the subject for any reason.	defined as a period from randomization to death of the subject for any reason (up to approximately 24 months)
tumor assessment	Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)	Baseline until disease progression or death, whichever occurs first (up to approximately 12 months)

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Anticipated): November 15, 2022
• Primary Completion (Anticipated): October 15, 2023
• Study Completion (Anticipated): March 15, 2024

Study Registration Dates

• First Submitted: July 7, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 1, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma (HCC); Locally Advanced or Metastatic
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: HLX10-009-HCC301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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