Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab

NCT06796114 | Recruiting

• 2 other identifiers: 2024-9312024-A02783-44
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 10

Brief Summary

Several cancer immunotherapies that target the PD-L1/PD-1 pathway (i.e., checkpoint inhibitors) show promising clinical activity in patients with HCC. In particular, atezolizumab selectively targets PD-L1 to prevent interaction with receptors PD-1 and B7-1, thus reversing T-cell suppression. Moreover, atezolizumab in combination with bevacizumab, a monoclonal antibody that targets VEGF and inhibits angiogenesis, is associated with an objective response rate of 27.3% (Cheng et al. 2021; Finn et al. 2020). This tumor response has led to FDA (Food and Drug Administration) and EMA (European Medicines Agency) approvals, in first-line treatment in unresectable HCC. Combinations studies evaluating anti-CTLA4 and anti-PD1/PDL1 antibodies displayed greater benefits (Abou-Alfa et al. 2022). In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, a single priming dose of tremelimumab (anti-CTLA-4) plus durvalumab (anti-PD-L1) in the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen significantly improved OS versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. In the HIMALAYA study, STRIDE regimen induced long term survival (defined as the absence of progression above 36 months following inclusion) in 103 out of the 393 patients exposed to this strategy (26%). The identification of biomarkers allowing the prediction of immunotherapy efficacy in HCC is still an unmet medical need.

Conditions

Hepatocellular Carcinoma

Keywords

biomarker, immunotherapy

Outcome Measures

Primary Outcomes (1)

• real-word overall survival

  defined as the delay from the date of treatment initiation to death from any cause

  through study completion, up to a maximum of 24 months after the inclusion of the last patient

Secondary Outcomes (3)

• real-word progression-free-survival

  through study completion, up to a maximum of 24 months after the inclusion of the last patient

• Objective Response Rate (ORR)

  through study completion, up to a maximum of 24 months after the inclusion of the last patient

• Disease control rate (DCR)

  through study completion, up to a maximum of 24 months after the inclusion of the last patient

Study Arms (1)

Blood sample

EXPERIMENTAL

Other: blood sample

Interventions

blood sample OTHER

A total of 48 ml of blood will be collected at baseline (before STRIDE initiation): * 6 EDTA 6 ml tubes for PBMC collection * 2 EDTA 6 ml tube for plasma collection

Blood sample

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Histologically confirmed hepatocellular carcinoma
• Locally advanced, metastatic, or unresectable disease
• Patient who had not previously received systemic anti-cancer treatment and are eligible to STRIDE therapy according to investigator decision in routine care and who have no contraindications to STRIDE treatment according to approved product label.
• Measurable disease defined according to RECIST v1.1 guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.)
• Age ≥ 18 years
• Patient affiliated to or beneficiary of French social security system
• Ability to comply with the study protocol, in the Investigator's judgment.

You may not qualify if:

• Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy.
• Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
• Patient under guardianship, curatorship or under the protection of justice

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• AstraZeneca: collaborator

Study Sites (10)

CHU de Besançon

Besançon, France

RECRUITING

CH de Chalon sur Saône

Chalon-sur-Saône, France

RECRUITING

CHU Grenoble

Grenoble, France

RECRUITING

CH de Mulhouse

Mulhouse, France

RECRUITING

Hôpital Beaujon - APHP

Paris, France

RECRUITING

Hôpital Henri Mondor - APHP

Paris, France

NOT YET RECRUITING

Hôpital La Pitié Salpêtrière - APHP

Paris, France

RECRUITING

CHU Poitiers

Poitiers, France

NOT YET RECRUITING

CHU de Reims

Reims, France

NOT YET RECRUITING

ICANS

Strasbourg, France

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Blood Specimen Collection

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Angélique VIENOT, Dr

CONTACT

+33 3 81 66 81 66; a3vienot@chu-besancon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 28, 2025
• Study Start: June 25, 2025
• Primary Completion (Estimated): June 25, 2027
• Study Completion (Estimated): January 31, 2030
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

FR (10)