156P A phase Ib/II study of nanatinostat (Nstat) plus valganciclovir (VGCV) in advanced Epstein-Barr virus positive (EBV+) solid tumors and with pembrolizumab (PEM) in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC)

Abstract

EBV is associated with NPC, with the virus in a latent state. Nstat is a Class-I selective oral HDAC inhibitor that induces expression of the lytic BGLF4 EBV protein kinase in EBV+ tumor cells, activating ganciclovir (GCV) via phosphorylation. This results in GCV-mediated inhibition of viral and cellular DNA synthesis and apoptosis. Nstat plus VGCV (oral prodrug of GCV) showed a favorable safety profile with anti-tumor activity in a phase 1b/2 study in R/R EBV+ lymphoma (recommended phase 2 dose [RP2D]: Nstat 20 mg daily [QD], 4 d/wk + VGCV 900 mg QD).