Hepatocellular Carcinoma (HCC)Phase 3NCT06841185
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 Phase 3 study testing HLX13, US-sourced YERVOY® and EU-sourced YERVOY® in people with Hepatocellular Carcinoma (HCC), run by Shanghai Henlius Biotech.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- HLX13, US-sourced YERVOY® and EU-sourced YERVOY®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 656 participants
- Where
- No sites listed yet
- Study dates
- 30 Apr 2025to 5 May 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- HLX13, US-sourced YERVOY®, EU-sourced YERVOY®
- Keywords
- Ipilimumab Biosimilar
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLX13Drug
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
US-sourced YERVOY®Drug
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
EU-sourced YERVOY®Drug
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
| Study group | Role | What they receive |
|---|---|---|
| HLX13 group | Experimental | Recombinant anti-CTLA-4 fully human monoclonal antibody injection developed by Shanghai Henlius Biotech, Inc. Receives: Drug: HLX13 |
| US-sourced YERVOY® group | Active comparator | US-sourced ipilimumab Receives: Drug: US-sourced YERVOY® |
| EU-sourced YERVOY® group | Active comparator | EU-sourced ipilimumab Receives: Drug: EU-sourced YERVOY® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: Up to Week 24
Secondary outcomes (26)
Maximum serum drug concentration (Cmax) after the first dose
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 21
Trough serum drug concentration (Ctrough) after the first dose
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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
Measured: Up to Day 21
Elimination half-life (t1/2) after the first dose
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 21
Total clearance (CL) after the first dose
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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
Measured: 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
Measured: Up to Day 85
Maximum serum drug concentration at steady state (Cmax, ss)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
Minimum serum drug concentration at steady state (Cmin, ss)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
Elimination half-life (t1/2) at steady state
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
Volume of distribution at steady state (Vss)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
Total clearance at steady state (CLss)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
Accumulation ratio of AUC (Rac, AUC)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
Accumulation ratio of Cmax (Rac, Cmax)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Day 85
ORR assessed by IRRC (based on RECIST v1.1)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: Up to Week 30
ORR assessed by investigators (based on RECIST v1.1)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to Week 48
Overall Survival (OS)
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Measured: 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
Measured: Up to Week 48
Adverse events (AEs)
Measured: Up to Month 15
Serious adverse events (SAEs)
Measured: Up to Month 15
Incidence of anti-drug antibodies (ADAs).
Measured: Up to 1 year
Incidence of neutralizing antibodies (NAbs).
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2025
- Study start30 Apr 2025 (estimated)
- Primary completion6 Jun 2027 (estimated)
- Study completion5 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Shanghai Henlius BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 656 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Henlius Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06841185
- Sponsor's protocol ID
- HLX13-HCC301
- Status last verified
- Feb 2025
- First submitted
- 18 Feb 2025
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06841185
- Acronym / sponsor ID
- HLX13-HCC301
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- Ipilimumab Biosimilar
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 656 participants (estimated)
- Lead sponsor
- Shanghai Henlius BiotechIndustry (pharma, biotech, devices)
- Study start
- 30 Apr 2025 (estimated)
- Primary completion
- 6 Jun 2027 (estimated)
- Study completion
- 5 May 2028 (estimated)
- First posted
- 24 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HLX13 group | Experimental | Drug: HLX13Recombinant anti-CTLA-4 fully human monoclonal antibody injection developed by Shanghai Henlius Biotech, Inc. |
| US-sourced YERVOY® group | Active comparator | Drug: US-sourced YERVOY®US-sourced ipilimumab |
| EU-sourced YERVOY® group | Active comparator | Drug: EU-sourced YERVOY®EU-sourced ipilimumab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HLX13HLX13 (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 | Drug | HLX13 group |
| 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 | Drug | US-sourced YERVOY® group |
| 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 | Drug | EU-sourced YERVOY® group |
Primary outcome
Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d)
Time frame: Up to Day 21
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Area under the serum concentration-time curve within a dosing interval at steady-state (AUCss)
Time frame: Up to Day 85
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Best Objective Response Rate (ORR) up to Week 24 (assessed by Independent Radiology Review Committee [IRRC] based on RECIST v1.1)
Time frame: Up to Week 24
Detailed Outcome Measure will be defined in the Statistical Analysis Plan
26 secondary outcomes
Maximum serum drug concentration (Cmax) after the first dose
Time frame: Up to Day 21
Trough serum drug concentration (Ctrough) after the first dose
Time frame: Up to Day 21
Time to reach maximum serum drug concentration (Tmax) after the first dose
Time frame: Up to Day 21
Elimination half-life (t1/2) after the first dose
Time frame: Up to Day 21
Total clearance (CL) after the first dose
Time frame: Up to Day 21
Volume of distribution during terminal phase (Vz) after the first dose
Time frame: Up to Day 21
Time to reach maximum serum drug concentration at steady state (Tmax, ss)
Time frame: Up to Day 85
Maximum serum drug concentration at steady state (Cmax, ss)
Time frame: Up to Day 85
Minimum serum drug concentration at steady state (Cmin, ss)
Time frame: Up to Day 85
Elimination half-life (t1/2) at steady state
Time frame: Up to Day 85
Volume of distribution at steady state (Vss)
Time frame: Up to Day 85
Total clearance at steady state (CLss)
Time frame: Up to Day 85
Accumulation ratio of AUC (Rac, AUC)
Time frame: Up to Day 85
Accumulation ratio of Cmax (Rac, Cmax)
Time frame: Up to Day 85
ORR assessed by IRRC (based on RECIST v1.1)
Time frame: Up to Week 30
ORR assessed by investigators (based on RECIST v1.1)
Time frame: Up to Week 48
Duration of Response (DOR) assessed by investigators (based on RECIST v1.1)
Time frame: Up to Week 48
Time to Response (TTR) assessed by investigators (based on RECIST v1.1)
Time frame: Up to Week 48
Progression-Free Survival (PFS) Status assessed by investigators (based on RECIST v1.1)
Time frame: Up to Week 48
Progression-Free Survival Rate (PFSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48
Time frame: Up to Week 48
Overall Survival (OS)
Time frame: Up to 1 year
Overall Survival Rate (OSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48
Time frame: Up to Week 48
Adverse events (AEs)
Time frame: Up to Month 15
Serious adverse events (SAEs)
Time frame: Up to Month 15
Incidence of anti-drug antibodies (ADAs).
Time frame: Up to 1 year
Incidence of neutralizing antibodies (NAbs).
Time frame: Up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HLX13, US-sourced YERVOY® and EU-sourced YERVOY® in people with Hepatocellular Carcinoma (HCC), run by Shanghai Henlius Biotech.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d) (time frame: Up to Day 21). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.