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

Not Applicable

Not yet recruiting

• Conditions: Hepatocellular Carcinoma

• Registration Number: NCT06796114
• Lead Sponsor: Centre Hospitalier Universitaire de Besancon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-10
• Study First Submitted QC: 2025-01-21
• Study First Posted: 2025-01-28
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-04
• Study Start: 2025-04-30
• Primary Completion: 2027-04-30
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Signed informed consent
2. Histologically confirmed hepatocellular carcinoma
3. Locally advanced, metastatic, or unresectable disease
4. 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.
5. 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.)
6. Age ≥ 18 years
7. Patient affiliated to or beneficiary of French social security system
8. Ability to comply with the study protocol, in the Investigator's judgment.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
real-word overall survival	through study completion, up to a maximum of 24 months after the inclusion of the last patient	defined as the delay from the date of treatment initiation to death from any cause

Secondary Outcome Measures

Name	Time	Method
real-word progression-free-survival	through study completion, up to a maximum of 24 months after the inclusion of the last patient	defined as the delay from the date of treatment initiation to the disease progression or death from any cause whichever occurs first, evaluated by RECIST criteria v1.1 and mRECIST.
Objective Response Rate (ORR)	through study completion, up to a maximum of 24 months after the inclusion of the last patient	defined as the addition of complete response and partial response rates, evaluated by RECIST citeria v1.1 and mRECIST
Disease control rate (DCR)	through study completion, up to a maximum of 24 months after the inclusion of the last patient	defined as the addition of complete response, partial response, and stable disease rates evaluated by RECIST criteria v1.1 and mRECIST.

Trial Locations

Locations (8)

CHU Grenoble; 🇫🇷 Grenoble, France

CH de Mulhouse; 🇫🇷 Mulhouse, France

CHU de Besançon; 🇫🇷 Besancon, France

CH de Chalon sur Saône; 🇫🇷 Chalon-sur-Saône, France

Hôpital Beaujon - APHP; 🇫🇷 Paris, France

Hôpital Henri Mondor - APHP; 🇫🇷 Paris, France

Hôpital La Pitié Salpêtrière - APHP; 🇫🇷 Paris, France

ICANS; 🇫🇷 Strasbourg, France