Hepatocellular CarcinomaIMMUNOGLYPICNCT05263830
Glypican-3 as a Prognostic Factor in Patients With Hepatocellular Carcinoma Treated by Immunotherapy
An observational study of Hepatocellular Carcinoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Recently, the positive results of the Imbrave 150 study (randomized study comparing Atezolizumab+Bevacizumab versus Sorafenib) prompted investigators to redefine their management strategy for advanced HCC by proposing the combination Atezolizumab+ Bevacizumab as first-line treatment in these patients. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Quantitative assay of GlypicanPC-3
- How many people
- 240 participants
- Where
- 1 siteFrance
- Study dates
- 8 Sep 2023to 8 Sep 2029
- Phase
- Observational
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with an indication for treatment with Atezolizumab/Bevacizumab for advanced HCC at a multidisciplinary consultation meeting
Who may be able to join
- 18 years ≤ age < 90 years
- Diagnosed with HCC developed on a cirrhotic liver or on chronic liver disease that has not reached the stage of cirrhosis regardless of the etiology diagnosed according to the diagnostic criteria for TNCD updated in June 2021 (1)
- Having an indication for systemic therapy with Atezolizumab+Bevacizumab validated in multidisciplinary meeting according to the current recommendations of cancer societies.
- Understanding the French language.
- Having been informed and accepted to participate to the study.
Who cannot join
- HIV or known immune deficiency or immunosuppressive treatment
- Autoimmune diseases or other immunotherapies
- History of portosystemic shunt or liver transplantation
- Sepsis, vasoconstrictor drugs.
- Pregnant or breastfeeding women
- Protected populations: under guardianship or curators
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Service hépato-gastroentérologie, Hôpital la Pitié-Salpêtrière
Paris, 75013
Manon Mme ALLAIRE, MD, 01 42 16 10 34 ext. +33, manon.allaire@aphp.fr
About this study
Official title: Evaluation of the Contribution of Glypican-3 as a Pronostic Factor in Patients With Advanced Hepatocellular Carcinoma Treated by Immunotherapy
Recently, the positive results of the Imbrave 150 study (randomized study comparing Atezolizumab+Bevacizumab versus Sorafenib) prompted investigators to redefine their management strategy for advanced HCC by proposing the combination Atezolizumab+ Bevacizumab as first-line treatment in these patients. Identifying new predictive biomarkers of response is essential to optimize the identification of patients who will benefit from immunotherapy. Glypican-3 (GPC-3) is a cell surface glycoprotein that belongs to the family of heparan sulfate chain proteoglycan that is directly implicated in several cancers and more particularly in HCC. GPC-3 overexpression in serum predicts a poor prognosis for patients with HCC and is associated with early tumor recurrence. Through this study, the investigators want to determine whether the concentration of circulating GPC-3 alone, or in combination with other biomarkers used in current practice (PIVKA, AFP) could predict the response to treatment with Atezolizumab/Bevacizumab and OS.
Read the detailed description
When hepatocellular carcinoma (HCC) is diagnosed, only 25% of patients will be able to have a curative treatment such as liver transplantation, treatment by ablation or surgical resection. In the majority of cases, patients will only have access to so-called palliative treatment. For many years, the only treatment available for patients with advanced HCC was sorafenib, a tyrosine kinase inhibitor with an average overall survival of 10.6 months. Recently, the positive results of the Imbrave 150 study (randomized study comparing Atezolizumab + Bevacizumab versus Sorafenib) prompted investigators to redefine their management strategy for advanced HCC by proposing the combination Atezolizumab+Bevacizumab as first-line treatment in these patients. Indeed, the overall survival (OS) and progression-free survival rates (PFS) were significantly higher in the Atezolizumab+Bevacizumab arm (OS: 67.2% at 12 months and PFS: 6.8 months) versus Sorafenib (OS: 54.6% at 12 months, PFS 4.3 months). The recent approval of the treatment in France is a unique opportunity to carry out a pilot study on clinical, biological, histological, molecular and immune prognostic and predictive factors in patients treated with the Atezolizumab+Bevacizumab combination. Identifying new predictive biomarkers of response is essential to optimize the identification of patients who will benefit from immunotherapy. HCCs are characterized by multiple genomic alterations and the abnormal expression of numerous pro- and anti-oncogenic genes. Glypican-3 (GPC-3) is a cell surface glycoprotein that belongs to the family of heparan sulfate chain proteoglycans. As a co-receptor, GPC-3 is involved in the control of several major signaling pathways (IGF2, Wnt/beta-catenin, etc.) and plays an important role in cell proliferation and tissue growth. At the tumoral level, GPC-3 is directly implicated in several cancers and more particularly in HCC. GPC-3 is overexpressed in 72% of HCCs and its expression is absent in normal liver tissues and benign liver lesions. GPC-3 overexpression is associated with the state of cell tumor differentiation and proliferation in HCC, tumor aggressiveness, as well as poor prognosis and shorter OS. GPC-3 overexpression in serum also predicts a poor prognosis for patients with HCC and is associated with early tumor recurrence. Through this study, the investigators want to determine whether the concentration of circulating GPC-3 alone, or in combination with other biomarkers used in current practice (PIVKA, AFP) could predict the response to treatment with Atezolizumab/Bevacizumab and OS.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Quantitative assay of GlypicanPC-3
- Keywords
- Hepatocellular carcinoma, Glypican 3, Immunotherapy
- Medical subject headings
- Carcinoma, Hepatocellular, Simpson-Golabi-Behmel syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quantitative assay of GlypicanPC-3Other
Quantitative assay of GlypicanPC-3 in human serum is performed by direct sandwich immunoassay ( CanAg Glypican3 EIA - Fujirebio ) on microplate using two mouse monoclonal antibodies against two epitopes of the Glypican-3 core protein
| Study group | Role | What they receive |
|---|---|---|
| Patient with hepatocellular carcinoma treated with Atezolizumab / Bevacizumab | Patients with an indication for treatment with Atezolizumab / Bevacizumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting. Receives: Other: Quantitative assay of GlypicanPC-3 | |
| Patient with hepatocellular carcinoma treated with Durvalumab/Trémélimumab | Patients with an indication for treatment with Durvalumab/Trémélimumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting. Receives: Other: Quantitative assay of GlypicanPC-3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
evaluate concentration of circulating GPC-3
Evaluation of the change in GPC-3 concentration before, at 3 weeks (second infusion) and at 3 months from the first infusion of Atezolizumab/Bevacizumab .
Measured: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab
Secondary outcomes (4)
Evaluate overall survival
Measured: at 24 months
Evaluation of the combination of circulating GPC-3 level with other biomarkers (PIVKA, AFP) before, 3 weeks and 3 months after initiation of Atezolizumab/Bevacizumab and/or their variation value could predict treatment response.
Correlation of the values of GPC-3, PIVKA, AFP
Measured: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab
Evaluation of the combination of circulating GPC-3 level with other biomarkers (PIVKA, AFP) before, 3 weeks and 3 months after initiation of Atezolizumab/Bevacizumab and/or their variation value could predict overall Survival.
Correlation between survival at 24 months and the values of GPC-3, PIVKA, AFP before, 3 weeks and 3 months after the start of treatment and the change in value.
Measured: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab, at 24 months
Evaluation of the HCC response to treatment on Imaging assessment (CT-scan and MRI) every 3 months according to the miRECIST criteria (combination of mRECIST and iRECIST criteria)
Measured: at inclusion, at 3,6,9,12,15,18,21 and 24 months of the first infusion of Atezolizumab/Bevacizumab,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2022
- Study start8 Sep 2023
- Primary completion8 Sep 2029 (estimated)
- Study completion8 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manon ALLAIRE, Dr, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05263830
- Sponsor's protocol ID
- APHP210978
- Acronym
- IMMUNOGLYPIC
- Status last verified
- Dec 2025
- First submitted
- 27 Jan 2022
- Last updated
- 16 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Contribution of Glypican-3 as a Pronostic Factor in Patients With Advanced Hepatocellular Carcinoma Treated by Immunotherapy
- ClinicalTrials.gov ID
- NCT05263830
- Acronym / sponsor ID
- IMMUNOGLYPIC / APHP210978
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular carcinoma, Glypican 3, Immunotherapy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 8 Sep 2023 (actual)
- Primary completion
- 8 Sep 2029 (estimated)
- Study completion
- 8 Sep 2029 (estimated)
- First posted
- 3 Mar 2022 (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.
Recently, the positive results of the Imbrave 150 study (randomized study comparing Atezolizumab+Bevacizumab versus Sorafenib) prompted investigators to redefine their management strategy for advanced HCC by proposing the combination Atezolizumab+ Bevacizumab as first-line treatment in these patients. Identifying new predictive biomarkers of response is essential to optimize the identification of patients who will benefit from immunotherapy. Glypican-3 (GPC-3) is a cell surface glycoprotein that belongs to the family of heparan sulfate chain proteoglycan that is directly implicated in several cancers and more particularly in HCC. GPC-3 overexpression in serum predicts a poor prognosis for patients with HCC and is associated with early tumor recurrence. Through this study, the investigators want to determine whether the concentration of circulating GPC-3 alone, or in combination with other biomarkers used in current practice (PIVKA, AFP) could predict the response to treatment with Atezolizumab/Bevacizumab and OS.
Detailed description
When hepatocellular carcinoma (HCC) is diagnosed, only 25% of patients will be able to have a curative treatment such as liver transplantation, treatment by ablation or surgical resection. In the majority of cases, patients will only have access to so-called palliative treatment. For many years, the only treatment available for patients with advanced HCC was sorafenib, a tyrosine kinase inhibitor with an average overall survival of 10.6 months. Recently, the positive results of the Imbrave 150 study (randomized study comparing Atezolizumab + Bevacizumab versus Sorafenib) prompted investigators to redefine their management strategy for advanced HCC by proposing the combination Atezolizumab+Bevacizumab as first-line treatment in these patients. Indeed, the overall survival (OS) and progression-free survival rates (PFS) were significantly higher in the Atezolizumab+Bevacizumab arm (OS: 67.2% at 12 months and PFS: 6.8 months) versus Sorafenib (OS: 54.6% at 12 months, PFS 4.3 months). The recent approval of the treatment in France is a unique opportunity to carry out a pilot study on clinical, biological, histological, molecular and immune prognostic and predictive factors in patients treated with the Atezolizumab+Bevacizumab combination. Identifying new predictive biomarkers of response is essential to optimize the identification of patients who will benefit from immunotherapy. HCCs are characterized by multiple genomic alterations and the abnormal expression of numerous pro- and anti-oncogenic genes. Glypican-3 (GPC-3) is a cell surface glycoprotein that belongs to the family of heparan sulfate chain proteoglycans. As a co-receptor, GPC-3 is involved in the control of several major signaling pathways (IGF2, Wnt/beta-catenin, etc.) and plays an important role in cell proliferation and tissue growth. At the tumoral level, GPC-3 is directly implicated in several cancers and more particularly in HCC. GPC-3 is overexpressed in 72% of HCCs and its expression is absent in normal liver tissues and benign liver lesions. GPC-3 overexpression is associated with the state of cell tumor differentiation and proliferation in HCC, tumor aggressiveness, as well as poor prognosis and shorter OS. GPC-3 overexpression in serum also predicts a poor prognosis for patients with HCC and is associated with early tumor recurrence. Through this study, the investigators want to determine whether the concentration of circulating GPC-3 alone, or in combination with other biomarkers used in current practice (PIVKA, AFP) could predict the response to treatment with Atezolizumab/Bevacizumab and OS.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient with hepatocellular carcinoma treated with Atezolizumab / Bevacizumab | – | Other: Quantitative assay of GlypicanPC-3Patients with an indication for treatment with Atezolizumab / Bevacizumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting. |
| Patient with hepatocellular carcinoma treated with Durvalumab/Trémélimumab | – | Other: Quantitative assay of GlypicanPC-3Patients with an indication for treatment with Durvalumab/Trémélimumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with an indication for treatment with Atezolizumab/Bevacizumab for advanced HCC at a multidisciplinary consultation meeting
Key inclusion criteria (5 listed)
- 18 years ≤ age < 90 years
- Diagnosed with HCC developed on a cirrhotic liver or on chronic liver disease that has not reached the stage of cirrhosis regardless of the etiology diagnosed according to the diagnostic criteria for TNCD updated in June 2021 (1)
- Having an indication for systemic therapy with Atezolizumab+Bevacizumab validated in multidisciplinary meeting according to the current recommendations of cancer societies.
- Understanding the French language.
- Having been informed and accepted to participate to the study.
Key exclusion criteria (6 listed)
- HIV or known immune deficiency or immunosuppressive treatment
- Autoimmune diseases or other immunotherapies
- History of portosystemic shunt or liver transplantation
- Sepsis, vasoconstrictor drugs.
- Pregnant or breastfeeding women
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 |
|---|---|---|
| Quantitative assay of GlypicanPC-3Quantitative assay of GlypicanPC-3 in human serum is performed by direct sandwich immunoassay ( CanAg Glypican3 EIA - Fujirebio ) on microplate using two mouse monoclonal antibodies against two epitopes of the Glypican-3 core protein | Other | Patient with hepatocellular carcinoma treated with Atezolizumab / Bevacizumab, Patient with hepatocellular carcinoma treated with Durvalumab/Trémélimumab |
Primary outcome
evaluate concentration of circulating GPC-3
Time frame: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab
Evaluation of the change in GPC-3 concentration before, at 3 weeks (second infusion) and at 3 months from the first infusion of Atezolizumab/Bevacizumab .
4 secondary outcomes
Evaluate overall survival
Time frame: at 24 months
Evaluation of the combination of circulating GPC-3 level with other biomarkers (PIVKA, AFP) before, 3 weeks and 3 months after initiation of Atezolizumab/Bevacizumab and/or their variation value could predict treatment response.
Time frame: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab
Evaluation of the combination of circulating GPC-3 level with other biomarkers (PIVKA, AFP) before, 3 weeks and 3 months after initiation of Atezolizumab/Bevacizumab and/or their variation value could predict overall Survival.
Time frame: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab, at 24 months
Evaluation of the HCC response to treatment on Imaging assessment (CT-scan and MRI) every 3 months according to the miRECIST criteria (combination of mRECIST and iRECIST criteria)
Time frame: at inclusion, at 3,6,9,12,15,18,21 and 24 months of the first infusion of Atezolizumab/Bevacizumab,
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 16 Dec 2025.
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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.
Manon ALLAIRE, Dr principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
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?
Contact Manon ALLAIRE, Dr (0142161034, manon.allaire@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
evaluate concentration of circulating GPC-3 (time frame: at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab). 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 16 Dec 2025.