On July 7, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported the e-publication of results from a Phase 1 company-sponsored study of oral rigosertib in combination with standard dose azacitidine in the treatment of patients diagnosed with either higher-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML) in the international hematological malignancy journal Leukemia Research (Press release, Onconova, JUL 7, 2020, View Source [SID1234561724]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"A key strategy emerging in the treatment of MDS is the identification of safe and effective combinations, particularly those involving oral agents. The results from this Phase 1 study represent Onconova’s first efforts to explore oral rigosertib in combination with azacitidine to address the unmet medical need in patients with MDS and AML. We anticipate meeting with the FDA, in conjunction with the pivotal data readout from the INSPIRE Trial, for alignment with the agency on a registration trial for the combination of oral rigosertib plus azacitidine in HMA-naïve HR-MDS," said Steven M. Fruchtman, M.D., President and CEO of Onconova.

"These results coupled with preliminary data from the phase II studies, support further clinical development of this novel combination with a manageable safety profile and efficacy in patients with MDS both those HMA naïve and after HMA failure," said study principal investigator Lewis R. Silverman, M.D., Director, Translational Research Center for the Myelodysplastic Syndrome, Associate Professor, Medicine, Hematology, and Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "The oral administration of rigosertib is not just more convenient for patients, but may improve treatment compliance, leading to improved clinical outcomes."

This publication reports the results of an open-label, dose-escalating Phase 1 study with the combination oral of rigosertib and standard dose azacitidine administered sequentially to patients diagnosed with HR-MDS following HMA-failure, or relapsed/refractory AML. The study objectives were to assess safety and determine the recommended Phase 2 dose (RP2D) for future studies. The study evaluated three dose cohorts of oral rigosertib with no dose-limiting toxicities reported. In addition, the oral rigosertib/azacitidine combination demonstrated an overall response rate of 7/9 (78%) in patients with HR-MDS and 2/7 (29%) in patients with AML. The Phase 2 part of the study is ongoing. Additional details are available on www.clinicaltrials.gov (NCT01926587).

"We believe this combination could eventually prove very beneficial for patients with higher-risk MDS. In addition to its oral formulation and thus ease of administration, rigosertib is potentially an attractive partner for a variety of combination approaches due to its novel mechanism of action as a RAS mimetic that differentiates it from other MDS therapies," said Richard C. Woodman, M.D., Chief Medical Officer of Onconova.

About Rigosertib

Rigosertib, Onconova’s lead candidate, is a proprietary Phase 3 small molecule. A key publication in a preclinical model reported rigosertib’s ability to block cellular signaling by targeting RAS effector pathways (Divakar, S.K., et al., 2016: "A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling." Cell 165, 643). Onconova is currently in the clinical development stage with oral and IV rigosertib, including clinical trials studying single agent IV rigosertib in second-line higher-risk MDS patients (pivotal Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in HMA naive and refractory higher-risk MDS patients (Phase 2). Patents covering oral and injectable rigosertib have been issued in the US and are expected to provide coverage until at least 2037.