Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors

In Phase I, no dose-limiting toxicities were reported and the MTD was not reached. The most common treatment-related adverse events were fatigue (42.9%) and nausea (42.9%). Grade 3-4 treatment-emergent adverse events occurred in 52.9% of patients, and 17.1% of patients experienced a fatal adverse event, with one death (asthenia) considered treatment-related. The overall objective response rate was 5.7%, with four partial responses. A significant reduction in intratumoral FoxP3+ regulatory T cells was observed after the azacitidine monotherapy run-in period, but no increase in intratumoral CD8+ T cells was observed. The authors note that epacadostat dosing may have been insufficient, as doses below 600 mg BID were not shown to reduce plasma kynurenine levels when combined with PD-1 inhibition. The regimen was not associated with substantial clinical response in immunotherapy-resistant solid tumors.