This paper reports the Phase 1 results from a Phase 1 / 2 study of patients with myelodysplastic syndromes, acute myeloid leukemia, and chronic myelomonocytic leukemia who had failed treatment with a hypomethylating agent. The addition of oral rigosertib to standard azacitidine resulted in a safety profile similar to standard dose single-agent azacitidine. The double therapy regimen produced an overall response rate of 56 percent. The findings support further clinical development of the novel sequential combination of oral rigosertib and standard dose azacitidine in patients with myeloid malignancies.