Résumé
BackgroundAnti-PD-(L)1 plus anti-VEGF or anti-CTLA-4 are the validated 1L immunotherapies of uHCC based on the results of IMbrave150, HIMALAYA and CheckMate-9DW studies. Here we present the results of the phase-2 of the phase-2/3 TRIPLET-HCC trial comparing ATEZO/BEV/IPI vs ATEZO/BEV (NCT05665348).MethodsThis French, prospective, multicenter, open-label study randomized 1:1 pts to arm A [ATEZO 1200 mg + BEV 15 mg/kg + IPI 1 mg/kg Q3W (4 doses)] or arm B [ATEZO 1200 mg + BEV 15 mg/kg Q3W] for 2 years. Phase-2 was non comparative with a primary endpoint of objective response rate (ORR) ≥ 35% in arm A as assessed per investigator by Recist 1.1 within the first 24 weeks (one-sided α-risk 10%, power 81%, exact binomial method). If positive, the trial will move to phase-3 with overall survival (OS)ResultsA total of 226 pts were randomized and analyzed in modified intention to treat (mITT) between arm A (n=113) and B (n=113) from March 2023 to September 2024 by 36 centers. With a power of 84%, ≥ 35 pts with objective response were needed in arm A to declare phase 2 as positive; only 34 pts showed objective response (30.1%, 80% CI: 24.4-36.3). In arm B, ORR was 27.4%, 80% CI: 22.0-33.5. With a median follow-up of 12.0 (Arm A) vs 12.5 months (mo) (Arm B), OS (median, 95% CI) was 22.6 mo (13.2-notConclusionsThis phase 2 did not meet its primary endpoint. Efficacy seemed to be similar between both arms whereas tolerance tended to be better in arm B. Finally, adding IPI at low dose (1 mg/kg) did not add benefit to ATEZO/BEV. A longer follow-up is needed to better assess the impact of IPI on OS, especially on the rate of long survivors.