1.Rigosertib, ON 01910.Na.is a novel small molecule inhibitor of critical pathways involved in the regulation of cell growth and division.Rigosertib inhibits the PI-3 Kinase and mitotic pathways and causes selective cytotoxicity in cancer cells.Both single agent and combination use of rigosertib are being explored in clinical trials.Clinical trials with rigosertib have enrolled more than 600 patients in USA, EU and Asia.2.Rigosertib in Hematological Cancers.Phase Ⅰ and Ⅱ clinical trials were conducted in high risk MDS (Int-1, Int-2, RAEB-t and CMML) and AML patients at four sites in the USA.Intravenous infusion ofrigosertib was administered over 48h, 72h or longer periods either at weekly or biweekly intervals.The effect of dose and duration of drug on bone marrow blast count were explored.Bone marrow response was noted in MDS and AML patient and was unrelated to karyotype or previous treatment history of these patients.Indeed, robust response was evident in patients who had previously failed hypomethylating agents.Good tolerability and some hematological improvement were also noted.Based on these results a multi-center randomized Phase Ⅲ clinical trial, with overall survival as an endpoint, is underway in the USA and EU.The design and rationale of this trial will be discussed.2.Rigosertib in Low-risk, Transfusion Dependent MDS.An oral formulation ofrigosertib has completed two Phase Ⅰ studies in MDS or solid tumor patients.In these trials, rigosertib was well tolerated and oral absorption was adequate and consistent.Oral rigosertib was active in both higher risk and low-risk MDS patients, as measured by bone marrow blast reduction and assessment of transfusion requirement.A Phase Ⅱ trial in low-risk, transfusion dependent MDS patients is now underway in the USA.In this study the endpoint is transfusion independence, as measured by WHO criteria.