Immune Cells as a New Biomarker of Response in Patients Treated by Immunotherapy for Advanced Hepatocellular Carcinoma

NCT05044676 | Terminated

• 1 other identifier: APHP210845
• Study Type: observational
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Treatment options for advanced HCC remain very limited. Until recently, multikinase inhibitor were the gold standard for advanced hepatocellular carcinoma but associated with poor outcome and important side effects. Recently, the positive results of the Imbrave 150 study (a randomized study comparing Atezolizumab + Bevacizumab versus Sorafenib) prompted us to redefine our management strategy for advanced hepatocellular carcinoma by proposing the combination of Atezolizumab/Bevacizumab as treatment first-line in patients with advanced hepatocellular carcinoma. However, only 1/3 of the patients will respond to the combination of treatment and identifying predictive factors of response and new immune checkpoint inhibitors in order to target more tumors appear as a major issue. In this context, recent work has underlined the importance of the activating CD226/DNAM-1 receptor as an original immunotherapeutic target in various cancers (solid and hematopoietic tumors). CD226 is a transmembrane receptor that is part of the immunoglobulin superfamily. It is expressed by most T lymphocytes (CD8+, CD4+), by Natural Killer (NK) cells, by promoting their cytotoxicity. The investigators propose to prospectively analyze the frequency and phenotype (expression of CD226) of circulating immune cells before the initiation of treatment with Atezolizumab/Bevacizumab, 3 weeks after the first injection and its variation to determine whether this biomarker could predict the response to the treatment.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; immunotherapy; immune cells; biomarkers

Outcome Measures

Primary Outcomes (4)

• Measurement of the frequency expression of CD226 at baseline

  at baseline

• Measurement of the frequency expression of CD226 3 weeks after the start of treatment

  3 weeks after the start of treatment

• Measurement of the phenotype of expression of CD226at baseline

  at baseline

• Measurement of the phenotype of expression of CD226 3 weeks after the start of treatment

  3 weeks after the start of treatment

Secondary Outcomes (3)

• Frequency of expression of CD226 to predict Overall survival (OS)

  at baseline and 3 weeks after the start of treatment

• phenotype expression of CD226 to predict Overall survival (OS)

  at baseline and 3 weeks after the start of treatment

• Correlation between pathology features (tumoral and non-tumoral liver) and the frequency and phenotype of expression of CD226

  At inclusion

Study Arms (1)

patients with hepatocellular carcinoma

Patients with an indication for treatment with Atezolizumab / Bevacizumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting.

Other: patients with hepatocellular carcinoma

Interventions

patients with hepatocellular carcinoma OTHER

The response of the hepatocellular carcinoma to treatment will be evaluated as part of the care

patients with hepatocellular carcinoma

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with an indication for treatment with Atezolizumab / Bevacizumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting (RCP).

You may qualify if:

• Advanced hepatocellular carcinoma with an indication of systemic therapy by Atezolizumab-Bevacizumab
• At least one measurable untreated lesion
• ECOS performance status of 0 or 1

You may not qualify if:

• HIV/ immunosuppressive treatment
• Active of history of autoimmune disease or immune deficiency
• Priori history of liver transplantation or systemic porto shunt
• Pregnant of breastfeeding women

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service hépato-gastroentérologie, Hôpital la Pitié-Salpêtrière

Paris, France, 75013, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Manon ALLAIRE, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: September 16, 2021
• Study Start: September 8, 2023
• Primary Completion: September 22, 2025
• Study Completion: September 22, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

FR (1)