Onconova Therapeutics announces three presentations relating to clinical trials of its Phase III-stage anticancer agent, rigosertib sodium (Estybon® or ON 01910.Na), at the 53rd American Society of Hematology (ASH) Annual Meeting in San Diego, CA, December 10-13, 2011. The presentations highlight data from five clinical trials with rigosertib for myelodysplastic syndrome (MDS) in both intravenous and oral formulations as well as identification of biomarkers employing a nano-immunoassay (NIA) in bone marrow cells from MDS patients in clinical trials.
Results of bone marrow blast response and overall survival in 60 patients with MDS treated with intravenous rigosertib are reported from four Phase I/II trials. A substantial proportion of patients had clinically significant reduction or stabilization in blasts (cancerous cells) and a correlation was evident between blast reduction and overall survival benefit. Rigosertib infusion showed no evidence of bone marrow toxicity. Principal investigators Azra Raza, M.D. (Columbia University Medical Center), Lewis R. Silverman, M.D. (Mount Sinai Medical Center), Matthew J. Olnes, M.D., Ph.D. (National Institutes of Health, NHLBI) and Peter L. Greenberg, M.D. (Stanford Cancer Institute) will report these results (Abstract #3822). Based on these studies a randomized Phase III survival trial of rigosertib treatment in high-risk MDS patients who have failed or progressed after receiving hypomethylating agents, the "ONTIME" trial (ON 01910.Na Trial In Myelodysplastic SyndromE), is now being conducted in more than 50 U.S. and European sites.
An oral dosage form of rigosertib has completed a Phase I dose escalation trial in MDS patients enrolled at the H. Lee Moffitt Cancer Center and Columbia University Medical Center, by Rami Komrokji, M.D. and colleagues, and Azra Raza, M.D., respectively (Abstract #3797). Pharmacodynamically relevant drug levels were achieved in MDS patients with the rigosertib capsule formulation. Signs of clinical activity were observed, including two cases of bone marrow responses in higher-risk patients refractory to hypomethylating agents, reduced needs for red cell transfusions in low-risk, transfusion-dependent patients, and transition to transfusion independence in some patients. Based on these results, Phase II studies will be conducted in Low or Intermediate-1 risk, transfusion-dependent MDS patients at Columbia and other sites.
A highly sensitive microfluidic nano-immunoassay (NIA) was employed to quantify phosphorylation of various signaling proteins in bone marrow cells of high-risk MDS patients before and after treatment with rigosertib by Alice C. Fan, M.D. and colleagues at Stanford University Cancer Institute (Abstract #3808). The reported results validate rigosertib-mediated inhibition of the PI3K and MAPK pathways critical to tumor cell survival. Detection of specific isoforms of phospho-MEK (in the MAPK signaling pathway) and phospho-AKT (in the PI3K pathway) provide potential biomarkers of rigosertib activity in MDS.