Personalized combination of neoadjuvant domatinostat, nivolumab and ipilimumab in macroscopic stage III melanoma patients stratified according to the interferon gamma signature …

TPS10087Background: Previous OpACIN and OpACIN-neo studies, investigating neoadjuvant ipilimumab (IPI) plus nivolumab (NIVO), demonstrated high pathologic response rates (74-78%) and favorable long-term outcomes in patients (pts) achieving pathologic response; at 36 and 18 months follow-up, respectively, only 1/71 (1.4%) pts with response has relapsed. In contrast, pts without pathologic response (pNR) have a poor prognosis; 15/23 (65.2%) have relapsed so far. This emphasizes the need for baseline biomarkers predictive of non-response and new neoadjuvant treatment combinations for these pts. In our previous studies, baseline interferon-gamma (IFN-γ) signature low pts were less likely to respond to neoadjuvant IPI plus NIVO. The DONIMI study tests the combination of NIVO +/- IPI with domatinostat (DOM), a class 1 histone deacetylase inhibitor, according to the IFN-γ signature in the tumor …