pembrolizumab + decitabine

Pembrolizumab + decitabine is an investigational combination immunotherapy regimen being evaluated in a Phase 2 neoadjuvant 'window' trial (NCT02957968) led by Virginia Commonwealth University for patients with locally advanced HER2-negative breast adenocarcinoma. The regimen consists of sequential administration of decitabine, a DNA methyltransferase inhibitor (hypomethylating agent), followed by pembrolizumab, a monoclonal antibody targeting the PD-1 immune checkpoint. The therapeutic rationale is that decitabine-induced hypomethylation can reverse epigenetic silencing of immune-related genes and tumor antigens, potentially 'priming' the tumor microenvironment to be more responsive to PD-1 blockade. This combination is administered prior to standard neoadjuvant chemotherapy (typically anthracycline, cyclophosphamide, and taxane-based) to increase tumor-infiltrating lymphocytes and improve pathologic complete response rates in both triple-negative and hormone receptor-positive, HER2-negative breast cancer subtypes.

Brand names

KeytrudaDacogen

Other names

pembrolizumabdecitabine5-aza-2'-deoxycytidine