Progress Report| Volume 55, ISSUE 4, P464-470, April 2023

Ipilimumab with atezolizumab-bevacizumab in patients with advanced hepatocellular carcinoma: The PRODIGE 81-FFCD 2101-TRIPLET-HCC trial

Published:February 16, 2023DOI:


      A substantial proportion of patients with hepatocellular carcinoma have to face up, sooner or later, to systemic therapy. The current standards as first line systemic therapies are either atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF), or durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4). However, the median overall survival remains below 20 months, and a minority of patients become long-term survivors. Of interest in immune-oncology strategies for hepatocellular carcinoma, the objective response seems to be the most reliable surrogate marker of better overall survival.
      TRIPLET-HCC (NCT05665348) is a multicentre, randomised, open-label phase II-III trial designed to evaluate efficacy and safety of the triple combination by the addition of ipilimumab (anti-CTLA-4) to atezolizumab/bevacizumab, versus the double atezolizumab/bevacizumab combination. The main inclusion criteria are histologically proven BCLC-B/C HCC without previous systemic therapy. The primary objective of the phase II is the objective response rate in the triple arm, and OS in the triple versus double arms in the phase III. Secondary endpoints common to the phases II and III are the comparisons of progression-free survival, objective response rates, tolerance and quality of life. In addition, genetic and epigenetic studies from tissue and circulating DNA/RNA will be conducted to assess their prognostic or predictive value.



      CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), DCR (disease control rate), DOR (duration of response), DSMB (data safety monitoring board), EHS (extra-hepatic spread), HCC (hepatocellular carcinoma), IO (immuno-oncology), ICI (immune-checkpoint inhibitors), irAE (immune-related adverse event), MIV (macrovascular invasion), mITT (modified intention-to-treat), ORR (objective response rate), OS (overall survival), PFS (progression-free survival), PD-L1 (Programmed death-ligand 1), PD-1 (Programmed cell Death protein 1), TKI (tyrosine kinase inhibitor), TTR (time to response), TTP (time to progression), TRAE (treatment-related adverse event), VEGF (Vascular Endothelial Growth Factor)
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