On March 09, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the publication of results from the ONTIME trial of intravenous (IV) rigosertib in higher-risk myelodysplastic syndromes (HR-MDS) in the top-tier, peer-reviewed journal, Lancet Oncology (Press release, Onconova, MAR 9, 2016, View Source [SID:1234509436]). The article, titled, "Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial," currently appears in the online edition, and will appear in an upcoming print issue of the journal. Schedule your 30 min Free 1stOncology Demo! 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 3 study of IV rigosertib, referred to as INSPIRE, which was initiated by Onconova in the fourth quarter of 2015.
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"This publication presents peer-reviewed results of the ONTIME trial with insights into the complexity of MDS, particularly in patients whose disease has failed the available HMA therapies," said Guillermo Garcia-Manero, MD, Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center, and lead author of the paper. "Rigosertib was well tolerated in patients with a high unmet medical need who have no approved therapeutic options. We are impressed by the trend to notable efficacy in well-defined, well-balanced subgroups of HR-MDS patients with very poor prognosis. Based on these findings, we have designed the new Phase 3 INSPIRE study with IV rigosertib, which is currently enrolling patients."
Steven Fruchtman, MD, Chief Medical Officer of Onconova added, "The INSPIRE trial is now open at multiple sites in the U.S., and we intend to initiate sites in Canada, Europe, Israel, and Australia. In addition, we are pleased that our commercial partner for Japan and Korea, SymBio Pharmaceuticals, Ltd., will also shortly begin enrolling patients for this study in Japan. We believe that publication of the ONTIME results in Lancet Oncology serves to highlight an important unmet medical need and the ongoing Phase 3 INSPIRE trial, and broadens the awareness of this pivotal study among physicians and patients."
About INSPIRE
The INternational Study of Phase III IV RigosErtib, or INSPIRE, is based on guidance received from the U.S. Food and Drug Administration and European Medicines Agency and derives from the findings of the ONTIME Phase 3 trial. INSPIRE is a multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients under 80 years of age who had progressed on, failed to respond to, or relapsed after previous treatment with an HMA within the first nine months of initiation of HMA treatment. This time frame optimizes the opportunity to respond to treatment with an HMA prior to declaring treatment failure, as per NCCN Guidelines.1 The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).
About Rigosertib
Rigosertib is a small molecule inhibitor of cellular signaling and acts as a Ras mimetic. These effects of rigosertib appear to be mediated by direct binding of the compound to the Ras-binding domain (RBD) found in many Ras effector proteins, including the Raf kinases and PI3K. The initial therapeutic focus for rigosertib is myelodysplastic syndromes (MDS), a group of bone marrow disorders characterized by ineffective formation of blood cells that often converts into acute myeloid leukemia (AML). Clinical trials for rigosertib are being conducted at leading institutions in the United States, Europe, and the Asia-Pacific region. Rigosertib is protected by issued patents (earliest expiry in 2026) and has been awarded Orphan Designation for MDS in the United States, Europe and Japan.