Onconova: Data Presentation From Combination Of Rigosertib And Azacitidine

(RTTNews) - Onconova Therapeutics Inc (ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, Sunday announced the presentation of data from clinical trials of rigosertib in myelodysplastic syndromes (MDS) and non-proliferative acute myeloid leukemia (AML) at the 56th American Society of Hematology (ASH) Annual Meeting in San Francisco.

Based on synergistic anti-leukemic activity of the combination of rigosertib and azacitidine demonstrated in non-clinical studies, an exploratory, dose-range finding study was conducted at Mount Sinai Medical Center (New York, NY) and the MD Anderson Cancer Center (Houston, TX).

"In this first-in-man Phase 1 trial, the combination of oral rigosertib and azacitidine was safely administered to patients with MDS or non-proliferative AML. Importantly, the addition of oral rigosertib to the standard dose of azacitidine did not worsen the adverse event profile compared to that reported for azacitidine alone," said Lewis Silverman, lead investigator and Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai.

"Furthermore, the rate of response observed in the Phase 1 portion of the study is promising and has led to the Phase 2 portion of this trial, which is now open at trial sites in the U.S. and Europe."

A total of 18 patients with MDS or non-proliferative AML, who were either previously untreated with hypomethylating agents (HMAs), or who had failed or progressed on an HMA, were included in this study. The indicated dose of azacitidine (75 mg/m2/day) was given in combination with escalating doses of oral rigosertib in three successive cohorts (140-560 mg given two times daily). Oral rigosertib was administered from day one through day 21 of a 28-day cycle. Azacitidine was administered for seven days starting on day eight of the 28-day cycle.

Nine patients with MDS, eight patients with AML and one patient with CMML received the combination. Responses according to International Working Group (IWG) criteria were observed. Marrow complete remission (mCR) was achieved in five patients (2 AML; 3 MDS). Complete remission with incomplete recovery of blood counts (CRi) was observed in four patients (1 AML; 3 MDS), and stable disease (SD) was observed in two patients (1 MDS; 1 CMML).

Measures of hematological improvement, including increases in platelet (1 AML; 2 MDS patients), erythroid (2 MDS patients) and neutrophil (2 MDS patients) counts were observed with the combination. Notably, two MDS patients who responded had previously failed treatment with a hypomethylating agent.

The most frequently reported adverse events in cycle 1 included constipation, diarrhea, nausea, fatigue, hypotension, and pneumonia. The adverse events did not differ significantly among the three dosing cohorts. The only adverse events of Grade 3 or greater that occurred in more than one patient were pneumonia, neutropenia, febrile neutropenia and thrombocytopenia.