A Study to Compare the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profile of HLX13 with YERVOY As a First-Line Treatment for Patients with Unresectable Hepatocellular Carcinoma

A Randomized, Multicenter, Double-Blind, Parallel-Controlled Integrated Phase I/III Clinical Study to Evaluate the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profile of Ipilimumab Biosimilar HLX13 Vs. YERVOY® (US-Sourced YERVOY® and EU-Sourced YERVOY®) As a First-Line Treatment for Patients with Unresectable Hepatocellular Carcinoma

This is a multicenter, randomized, double-blind, parallel-controlled integrated phase I/III clinical study to evaluate the efficacy, safety, PK, and immunogenicity of HLX13 and YERVOY® in patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: HLX13; Drug: US-sourced YERVOY®; Drug: EU-sourced YERVOY®

Detailed Description

This study includes three treatment groups. Patients will be randomly assigned at a 2:1:1 ratio to the HLX13, US-sourced YERVOY®, or EU-sourced YERVOY® group to receive the treatment of IMPs in combination with nivolumab.

Patients with good tolerability and disease control will receive HLX13 or YERVOY® in combination with nivolumab on the first day of every 3 weeks for up to 4 cycles. PK and immunogenicity blood sampling will be conducted during the treatment period. After the four treatment cycles, all subjects will be subsequently treated with nivolumab monotherapy until investigator-assessed disease progression, initiation of a new anti-neoplastic therapy, withdrawal of informed consent, death, unacceptable toxicity, or up to 1 year after randomization, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 656
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically diagnosed relapsed metastatic or advanced hepatocellular carcinoma not eligible for surgical or locoregional therapies according to the diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD).
• At least one measurable lesion as assessed by IRRC based on RECIST v1.1 within 4 weeks prior to the first dose in this study.
• No systemic therapy for relapsed metastatic or advanced hepatocellular carcinoma prior to screening.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Child-Pugh Class A.
• Normal major organ functions.
• Women of childbearing potential should use highly effective methods of contraception during the study and within 5 months after the last study treatment; Male subjects capable of fathering a child must agree to use at least one highly effective method of contraception for the duration of the study and for at least 7 months after the last study treatment.

Exclusion Criteria:

• With other histopathological types of hepatocellular carcinoma.
• History of hepatic encephalopathy.
• Clinically significant ascites.
• Patients with tumor thrombus at the main portal vein, left or right portal (either or both) vein branch, or inferior vena cava.
• Presence of the central nervous system disorders at screening, except subjects who have previously received treatment for brain metastases can participate in the study treatment if their clinical symptoms have been stable for at least 4 weeks.
• Evidence of portal hypertension with bleeding esophageal or gastric varices within 6 months prior to the randomization.
• Known active or suspected autoimmune diseases.
• Active co-infection with both hepatitis B and C, or hepatitis D infection in subjects with hepatitis B.
• Uncontrolled cardiovascular diseases within 6 months.
• Known interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, and severe lung function abnormalities that may impede the investigators' diagnosis and management of drug-related pulmonary toxicity prior to screening.
• Patients who have received any T-cell costimulatory agents or immune checkpoint blockade therapy, including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other agents that target T cells.
• Patients who have other conditions not suitable for inclusion per investigator's judgments.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX13 group; Recombinant anti-CTLA-4 fully human monoclonal antibody injection developed by Shanghai Henlius Biotech, Inc.	Drug: HLX13; HLX13 (3 mg/kg) and nivolumab (1 mg/kg) treatment on the first day of each cycle, every 3 weeks with a total of 4 cycles
Active Comparator: US-sourced YERVOY® group; US-sourced ipilimumab	Drug: US-sourced YERVOY®; US-sourced YERVOY® (3 mg/kg) and nivolumab (1 mg/kg) treatment on the first day of each cycle, every 3 weeks with a total of 4 cycles
Active Comparator: EU-sourced YERVOY® group; EU-sourced ipilimumab	Drug: EU-sourced YERVOY®; EU-sourced YERVOY® (3 mg/kg) and nivolumab (1 mg/kg) treatment on the first day of each cycle, every 3 weeks with a total of 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Area under the serum concentration-time curve within a dosing interval at steady-state (AUCss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Best Objective Response Rate (ORR) up to Week 24 (assessed by Independent Radiology Review Committee [IRRC] based on RECIST v1.1)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum drug concentration (Cmax) after the first dose	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Trough serum drug concentration (Ctrough) after the first dose	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Time to reach maximum serum drug concentration (Tmax) after the first dose	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Elimination half-life (t1/2) after the first dose	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Total clearance (CL) after the first dose	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Volume of distribution during terminal phase (Vz) after the first dose	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 21
Time to reach maximum serum drug concentration at steady state (Tmax, ss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Maximum serum drug concentration at steady state (Cmax, ss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Minimum serum drug concentration at steady state (Cmin, ss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Elimination half-life (t1/2) at steady state	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Volume of distribution at steady state (Vss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Total clearance at steady state (CLss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Accumulation ratio of AUC (Rac, AUC)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
Accumulation ratio of Cmax (Rac, Cmax)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Day 85
ORR assessed by IRRC (based on RECIST v1.1)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 30
ORR assessed by investigators (based on RECIST v1.1)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 48
Duration of Response (DOR) assessed by investigators (based on RECIST v1.1)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 48
Time to Response (TTR) assessed by investigators (based on RECIST v1.1)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 48
Progression-Free Survival (PFS) Status assessed by investigators (based on RECIST v1.1)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 48
Progression-Free Survival Rate (PFSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 48
Overall Survival (OS)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to 1 year
Overall Survival Rate (OSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	Up to Week 48
Adverse events (AEs)		Up to Month 15
Serious adverse events (SAEs)		Up to Month 15
Incidence of anti-drug antibodies (ADAs).		Up to 1 year
Incidence of neutralizing antibodies (NAbs).		Up to 1 year

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2025
• Primary Completion (Estimated): June 6, 2027
• Study Completion (Estimated): May 5, 2028

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: February 21, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Ipilimumab Biosimilar
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Ipilimumab
• Other Study ID Numbers: HLX13-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
• product manufactured in and exported from the U.S.: No