RecruitingNot ApplicableNCT06796114

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

Sponsor

Centre Hospitalier Universitaire de Besancon

Enrollment

120 participants

Start Date

Jun 25, 2025

Study Type

INTERVENTIONAL

Conditions

Hepatocellular Carcinoma

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

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.

Exclusion Criteria3

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

Interventions

OTHERblood sample

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