Onconova Therapeutics Inc. announced that two presentations regarding the development of an oral formulation of rigosertib (Estybon, ON 01910.Na) for patients with solid tumors and myelodysplastic syndromes (MDS) will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 1-5, in Chicago.
Collectively, these presentations form the basis for further development of oral rigosertib in solid tumor and MDS patients. Recently, Onconova initiated a Phase 2 trial named ONTARGET (Oral ON 01910.Na in TrAnsfusion-RequirinG patients with myElodysplasTic syndrome), studying a transfusion-dependent low-risk MDS patient population.
Rigosertib, which employs a novel mechanism of action, has been shown to be active in both solid tumors and hematologic cancers. The intravenous formulation of rigosertib is in a pivotal Phase III trial (designated ONTIME, ON 01910.Na Trial In Myelodysplastic SyndromE), which is evaluating rigosertib in high-risk MDS patients. Rigosertib also is being evaluated in several Phase 1and 2 clinical trials at major medical centers in the USA and abroad. Overall, rigosertib has been administered to more than 600 cancer patients in clinical trials either as a single agent or in combination with chemotherapy.
Twenty-five patients with histologically confirmed solid tumors refractory to standard therapy were given escalating doses of oral rigosertib twice daily. Doses were increased according to a schedule until the appearance of grade 2 or grade 3/4 toxicities. The maximum tolerated dose (MTD) of oral rigosertib administered twice daily continuously is 560 mg. Dysuria was identified as a potential dose-limiting adverse event and a reported toxicity. The investigators found that dysuria could be successfully managed by ensuring oral hydration and administering sodium bicarbonate. The antitumor activity in this study supported past observations of rigosertib efficacy in other solid tumor clinical trials. Pharmacokinetic (PK) data reveal plasma levels with oral rigosertib were above the predicted pharmacodynamically active levels. Final safety and efficacy results, plasma and urinary PK relationships, and mutational analyses from arc hival tissue were be presented at ASCO.
In another Phase 1study, the investigators found orally-delivered rigosertib to be well tolerated and readily bioavailable under fasting conditions. Observations of clinical activity included reductions of bone marrow blasts in high-risk MDS patients who were refractory to hypomethylating agents and reductions red blood cell (RBC) transfusions in transfusion-dependent patients, with a transition to transfusion independence. This trial and subsequent evaluations could demonstrate that oral administration of rigosertib is preferred over intravenous infusion.
Release Date: June 1, 2012
Source: Onconova Therapeutics Inc.
Filed Under: Drug Discovery