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.
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.
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
Single group
blood sample
Other interventionA 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
real-word overall survival
defined as the delay from the date of treatment initiation to death from any cause
real-word progression-free-survival
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)
defined as the addition of complete response and partial response rates, evaluated by RECIST citeria v1.1 and mRECIST
Disease control rate (DCR)
defined as the addition of complete response, partial response, and stable disease rates evaluated by RECIST criteria v1.1 and mRECIST.
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Centre Hospitalier Universitaire de Besancon
Lead sponsor
AstraZeneca
Collaborator
