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

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.
Competing Interests: Conflict of interest • B.G. has participated in consulting and/or advisory boards for Roche, AstraZeneca, BMS, Bayer, Ipsen, and received research grant from Roche. • C.C. has participated in consulting and/or advisory boards for Ipsen, Gilead, Abbvie, Intercept and received research grant from Gilead. • D.T. has participated in consulting and/or advisory boards for AstraZeneca, Pierre Fabre, Ipsen, MSD, BMS, Servier, Sirtex Medical, Novartis and AMGEN • E.A.: Consulting: BMS, AstraZeneca, Bayer, Roche, Ipsen, Incyte, Servier, Boston Scientific, AAA; Travel expense: IPSEN, MSD • H.S. report lecture fee, board membership, or consultancy from Amgen, Fresenius, IPSEN, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, Abbvie, has stocks from Enterome bioscience and is co-founder of Exeliom Biosciences. • J.C.N. has received research grants from Ipsen and Bayer. • J.E.: Consulting: MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene, Taiho, Boston Scientific; Travel expense: Amgen; Research funding (institutional): BMS, Beigene, Boston Scientific • J.F.B.: Bayer, Ipsen, Esai, Astra-Zeneca, Roche, BMS, Servier, Incyte, Tahio Oncology • J.M.P. has participated in consulting and/or advisory boards for Roche, AstraZeneca, Eisai, MSD, Bayer, Ipsen, Lilly • K.L.M.: No conflict of interests • M.A. has participated in consulting and/or advisory boards for AstraZeneca, Bayer and Roche. • M.B. has participated in consulting and/or advisory boards for Bayer, AstraZeneca, Roche, Ipsen, MSD, BMS, Servier, Sirtex Medical, Eisai, Taiho • M.G.: No conflict of interests • P.M. has participated in consulting and/or advisory boards for Roche, AstraZeneca, Eisai, MSD, Bayer, Ipsen, and received research grants from Genosciences and Ipsen. • P.L.P.: is a consultant/advisory board member for Merck Serono, AstraZeneca Amgen, Boehringer Ingelheim, Biocartis, Roche, Bristol-Myers Squibb, Pierre Fabre, Servier, and MSD. • T.A.: has participate in consulting and/or advisory boards for Servier, Pierre Fabre, MSD and BMS and received grant from Amgen
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