Results of ONTIME phase III trial of Estybon (rigosertib) in myelodysplastic syndromes published in Lancet Oncology- Onconova

Onconova Therapeutics has announced the publication of results from the ONTIME trial of intravenous (IV) Estybon (rigosertib) in higher-risk myelodysplastic syndromes (HR-MDS) in the Lancet Oncology. The ONTIME trial was a randomized clinical study in HR-MDS patients following the failure of hypomethylating agents (HMAs). Overall survival was the primary endpoint in this international study of 299 patients. Although there was a trend to improvement in overall survival with IV rigosertib, no statistically significant difference was observed in the intention-to-treat (ITT) analysis between treatment and control (best supportive care, BSC) arms. Analyses in multiple clinically-important subgroups suggested that rigosertib may provide a meaningful survival benefit over BSC in some HR-MDS patients, including those with primary HMA failure (i.e., never benefited from first-line treatment with HMAs).

Additionally, those HR-MDS patients who were classified as Very High Risk by the International Prognostic Scoring System (Revised), and patients with monosomy 7 or trisomy 8 chromosomal aberrations, showed encouraging overall survival results with rigosertib. Collectively, these results helped define a more homogenous patient population for a new Phase III study of IV rigosertib, referred to as INSPIRE, which was initiated by Onconova in the fourth quarter of 2015.

Comment: Onconova has been notified that Baxter Healthcare SA, Onconova's commercialization partner in Europe, has elected not to pursue additional clinical trials, or the submission of a drug approval application, for rigosertib oral in low risk MDS patients.