Introduction
murine colon carcinoma, tumor, melanoma, BRAF-mutant melanoma
TUMOR, MELANOMA, STAGE III MELANOMA
To date, standard treatment for patients with macroscopic stage III melanoma includes surgery followed by adjuvant immune checkpoint blockade (ICB) directed against programmed death-1 (anti-PD-1) or adjuvant BRAF/MEK-targeted therapy for those with BRAF-mutant melanoma. However, growing evidence from preclinical studies (In our previous OpACIN-neo trial testing different dosing schedules of neoadjuvant ipilimumab + nivolumab in stage III melanoma, we identified the 10-gene IFN-γ signature (Histone deacetylase inhibitors (HDACi) are epigenetic modifiers known to have direct anti-tumor effects in melanoma (Domatinostat, a selective class I HDAC inhibitor, has been shown to synergize with PD-L1 blockade in murine colon carcinoma models (Here, we present preclinical evidence for combining domatinostat with anti-PD-1 ± anti-CTLA-4 in a melanoma tumor model, and report the first results of the DONIMI trial (NCT04133948). This phase 1b trial investigated the feasibility, safety, and efficacy of different combinations of neoadjuvant nivolumab ± ipilimumab with domatinostat in patients with stage III melanoma, stratified according to the IFN-γ score from a baseline tumor biopsy.