Phase I Clinical Study To Evaluate Pharmacokinetic Profile, Safety, Efficacy and Immunogenicity Of Ipilimumab Biosimilar HLX13 Vs. YERVOY® (US-Sourced YERVOY®) As A First-Line Treatment For Patients With Unresectable Hepatocellular Carcinoma
A Randomized, Multicenter, Double-Blind, Parallel-Controlled, Phase I Clinical Study To Evaluate Pharmacokinetic Profile, Safety, Efficacy and Immunogenicity Of Ipilimumab Biosimilar HLX13 Vs. YERVOY® (US-Sourced YERVOY®) As A First-Line Treatment For Patients With Unresectable Hepatocellular Carcinoma
1 other identifier
interventional
246
2 countries
51
Brief Summary
This is a multicenter, randomized, double-blind, parallel-controlled, phase I clinical study to evaluate the PK characteristics, safety, efficacy, and immunogenicity of HLX13 and US-sourced YERVOY® in patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2025
51 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 1, 2025
CompletedFirst Posted
Study publicly available on registry
September 16, 2025
CompletedStudy Start
First participant enrolled
November 25, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
March 16, 2026
March 1, 2026
1 year
September 1, 2025
March 12, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d) after the 1st dose
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
from time 0 to 21 days after the 1st dose (3 weeks)
Area under the serum concentration-time curve within a dosing interval at steady-state (AUCss) after the 4th dose
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
from time 0 to 78 days after the 4th dose (20 weeks)
Secondary Outcomes (17)
Maximum serum drug concentration (Cmax)
from time 0 to 78 days after the 4th dose (20 weeks)
Maximum serum drug concentration at steady-state (Cmax,ss)
from time 0 to 78 days after the 4th dose (20 weeks)
Trough serum drug concentration (Ctrough)
from time 0 to 78 days after the 4th dose (20 weeks)
Trough serum drug concentration at steady-state (Ctrough,ss)
from time 0 to 78 days after the 4th dose (20 weeks)
Time to reach maximum serum drug concentration (Tmax)
from time 0 to 78 days after the 4th dose (20 weeks)
- +12 more secondary outcomes
Study Arms (2)
HLX13 Group
EXPERIMENTALUS-sourced YERVOY® Group
ACTIVE COMPARATORInterventions
Patients will receive HLX13 (3 mg/kg) treatment on the first day of each 3-week cycle, up to 4 cycles.
Patients will receive US-sourced YERVOY® (3 mg/kg) treatment on the first day of each 3-week cycle, up to 4 cycles.
Patients will receive EU-sourced OPDIVO® (EU-sourced nivolumab) (1 mg/kg) treatment on the first day of each 3-week cycle, up to 4 cycles. Subjects who may continue to benefit from OPDIVO® treatment as assessed by investigators will be subsequently treated with local-sourced OPDIVO® monotherapy every 4 weeks, up to 2 year after randomization.
Eligibility Criteria
You may qualify if:
- Subjects must have signed and dated an IRB/IEC-approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines.
- Male or female, 18 years ≤ age ≤ 65 years at the time of signing the ICF.
- Body weight: 50 kg-85 kg.
- Histologically diagnosed hepatocellular carcinoma (HCC); and must have an advanced HCC, defined as: a) not eligible for curative surgical and/or locoregional therapies; or b) progressive disease after surgical and/or locoregional therapies. Subjects with only a radiologic diagnosis of hepatocellular carcinoma may be enrolled for screening in the study but histological confirmation is mandatory prior to randomization.
- At least one measurable lesion as assessed by investigator based on RECIST v1.1 within 4 weeks prior to the first dose in this study. The measurable lesion is not from sites that have been previously treated with surgery, radiotherapy, and/or locoregional therapy.
- No systemic therapy for relapsed metastatic or advanced hepatocellular carcinoma prior to screening. Note: prior neo-adjuvant or adjuvant systemic therapy is permitted if recurrence occurs ≥12 months after treatment completion.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 within 7 days prior to the first dose.
- Cirrhotic status of Child-Pugh Class A within 7 days prior to the first dose.
- Left ventricular ejection fraction (LVEF) ≥ 50% as measured by echocardiography.
- Normal major organ functions prior to the first dose.
- For patients with active hepatitis B virus (HBV), the HBV-DNA must be less than 500 IU/mL or 2500 copies/mL within 28 days prior to the randomization, an anti-HBV treatment (e.g., entecavir) has been started prior to the randomization, and patients are willing to continue the treatment during this study. Patients with positive HCV-RNA must agree to receive standard anti-viral therapy per the local standard of care.
- Women of childbearing potential should have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to the first dose.
You may not qualify if:
- With other histopathological types of hepatocellular carcinoma, including fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or mixed cholangiocarcinoma and hepatocellular carcinoma.
- Other malignancies active within 3 years prior to or at screening except for localized tumors that have been cured such as basal cell carcinoma, squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
- Liver transplant, or organ allograft or allogeneic bone marrow transplantation prior to screening, or the above transplantation is scheduled during the study.
- History of hepatic encephalopathy prior to screening.
- Clinically significant ascites.
- Patients with tumor thrombus at the main portal vein (Vp4), or inferior vena cava prior to screening, or clear invasion into the bile duct, or HCC with ≥50% liver occupation.
- Presence of nervous system disorders at screening.
- Evidence of portal hypertension with bleeding esophageal or gastric varices within 6 months prior to the randomization. The aforementioned patients have undergone endoscopy to exclude those with high hemorrhage risk may be enrolled. For a patient receiving endoscopy within 6 months prior to randomization, repeat examination is not required.
- Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 3 months prior to screening except for esophageal or gastric varices.
- History of non-healing wounds, bone fractures, or ulcers at risk of bleeding within 3 months prior to randomization.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the randomization or those who receive minor surgical procedures (e.g., core biopsy) within 7 days prior to randomization.
- Known active or suspected autoimmune diseases prior to screening. Patients with stable disease who do not require systemic immunosuppressive therapy may also participate.
- Treatment with systemic corticosteroids (\> equivalent dose of 10 mg/day prednisone) or other immunosuppressive agents within 14 days prior to the first dose or during the study. However, for patients with conditions other than active autoimmune diseases, inhaled or topical steroids or adrenocortical hormone replacement therapy (no more than the equivalent dose of 10 mg/day prednisone) are allowed.
- Active co-infection with both hepatitis B and C (or detectable HBV surface antigen or HBV-DNA and HCV-RNA at screening), or hepatitis D infection in subjects with hepatitis B.
- Subjects with a history of co-infection with both hepatitis B and C.
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (51)
Oncology Physicians Network (OPN) - Los Alamitos /OPN Healthcare
Glendale, California, 91203, United States
Los Angeles Cancer Network
Glendale, California, 91204, United States
Cancer Specialists of North Florida
Jacksonville, Florida, 32256, United States
D&H National Research Centers, LLC
Margate, Florida, 33063, United States
Mid Florida Hematology and oncology Center
Orange City, Florida, 32763, United States
Florida Clinical Trials Group
Plantation, Florida, 33322, United States
Florida Clinical Trials Group
Tamarac, Florida, 33321, United States
HCA Research Institute, LLC
Brentwood, Tennessee, 37027, United States
Oncology Consultants
Houston, Texas, 77030, United States
American Oncology Network Vista Oncology Division/Physician Partner Associate
Olympia, Washington, 98506, United States
Northwest Medical Specialties PLLC (NWMS)
Tacoma, Washington, 98405, United States
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, China
Peking Union Medical College Hospital
Beijing, China
Peking university international hospital
Beijing, China
The First Affiliated Hospital of Bengbu Medical University
Bengbu, China
JiLin Cancer Hospital
Changchun, China
The First Hospital of Jilin University
Changchun, China
People's Hospital of Hunan Province
Changsha, China
Chengdu Fifth People's Hospital
Chengdu, China
Sichuan Cancer Hospital
Chengdu, China
Dongguan People's Hospital
Dongguan, China
Fujian Cancer Hospital
Fuzhou, China
Ganzhou People's Hospital
Ganzhou, China
Nanfang Hospital, Southern Medical University
Guangzhou, China
Hainan General Hospital
Haikou, China
Sir Run Run Shaw Hospital Affiliated with Zhejiang University School of Medicine
Hangzhou, China
Harbin Medical University Cancer Hospital
Harbin, China
The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
Hefei, China
Jinan Central Hospital
Jinan, China
Affiliated Hospital of Jining Medical University
Jining, China
Linyi Cancer Hospital
Linyi, China
Lishui Central Hospital
Lishui, China
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, China
Jiangxi Cancer Hospital
Nanchang, China
The Second Affiliated Hospital of Nanchang University
Nanchang, China
Jiangsu Province Hospital
Nanjing, China
The Affiliated Hospital of Nanjing university Medical School
Nanjing, China
Guangxi Medical University Cancer Hospital
Nanning, China
Fudan University Shanghai Cancer Center
Shanghai, China
Shanghai Gobroad Cancer Hospital
Shanghai, China
Zhongshan Hospital, Fudan University
Shanghai, China
Liaoning Cancer Hospital & Institute
Shenyang, China
Shengjing Hospital of China Medical University
Shenyang, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, China
Hubei Cancer Hospital
Wuhan, China
Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology
Wuhan, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
The First Affiliated Hospital of Xi 'an Jiaotong University
Xi'an, China
Henan Cancer Hospital
Zhengzhou, China
The first affiliated hospital of zhengzhou university
Zhengzhou, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 1, 2025
First Posted
September 16, 2025
Study Start
November 25, 2025
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
March 16, 2026
Record last verified: 2026-03