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

Condition(s) studied

Investigational drug(s) / intervention(s)

blood 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

Study 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

Primary outcome measure(s)

• 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

Trial sites (10)

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