An open-label, phase II basket study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors

Purpose: To evaluate whether administration of the oral DNA hypomethylating agent (HMA) CC-486 enhances the poor response rate of immunologically ‘cold’ solid tumors to immune checkpoint inhibitor durvalumab. PD-L1/PD-1 inhibitor naïve patients with advanced microsatellite stable colorectal cancer; platinum resistant ovarian cancer; and estrogen receptor positive, HER2 negative breast cancer were enrolled in this single-institution, investigator-initiated trial. Two 28-day regimens, regimen A (CC-486 300mg QD Days 1-14 (cycles 1-3 only) in combination with durvalumab 1500mg IV Day 15) and regimen B (CC-486 100 mg QD Days 1-21 (cycles 1-3 only), vitamin C 500mg QD continuously and durvalumab 1500mg IV Day 15) were investigated. Patients underwent paired tumor biopsies and serial peripheral blood mononuclear cells (PBMCs) collection for immune-profiling, transcriptomic, and epigenomic analysis. Transcriptomic data presented here.