Public HealthIOPHARM Presents Positive Indibulin Translational And Dose Scheduling Data At ASCO
ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced today that it presented positive data from both a Phase Ib clinical trial and preclinical dosing studies of orally administered indibulin (ZybulinTM or ZIO-301), the Company"s novel tubulin binding agent, at the 45th Annual American Society of Clinical Oncology (ASCO) meeting held in Orlando, FL, May 29th to June 2nd.
In the Phase Ib study, oral indibulin was administered with oral capecitabine (XelodaTM) in patients with advanced solid tumors. Trial results presented are for 7 patients who had received a median of three prior therapies. All 7 patients were evaluable for safety, and 4 for efficacy. Three patients had stable disease for a minimum of 6 cycles with 1 patient ongoing in their 11th cycle of treatment. There were no dose limiting toxicities and therefore no maximum tolerated dose was established. Adverse events included hand-and-foot syndrome (capecitabine), fatigue, vomiting, loss of appetite and headaches, and were easily managed. There was no reported neurotoxicity, consistent with other Phase I and preclinical data with indibulin. There was early activity seen in breast, colon, bladder and prostate cancers with this sub-optimal dose level and schedule, which is encouraging with regard to further study using mathematically-optimized dose scheduling, the subject of the preclinical data also presented.
The preclinical results were derived from mathematical modeling applying Norton-Simon models in breast cancer xenografts. The work was conducted by the Company under the direction of Dr. Larry Norton (Harmon Hill). Formal analyses revealed that the major effect of therapy occurs in five days of exposure, which is not manifest on gross inspection until one week thereafter. Therefore an intermittent schedule based on five days of drug administration preserves full activity while minimizing the possibility of toxicity. A Phase I/II study in breast cancer using this highly novel scheduling strategy is in development under the direction of two leading breast cancer specialists, Dr. Clifford Hudis in the United States and Dr. Jose Baselga in Spain.
"Indibulin is not only an interesting drug because it is active against taxane-resistant cells without the neurotoxicity seen with all the other tubulin binding agents, but also because mathematical modeling has revealed a novel dose-schedule that promises to maximize efficacy and minimize toxicity in the clinic. Also, it is oral, so it is potentially of value to the entire world"s population", commented Dr. Larry Norton, senior author on this presentation.
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ZIOPHARM Oncology, Inc.