Clinical efficacy of the antitumor agent ONC201 in GBM

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 DESCRIPTION (provided by applicant): ONC201 is a clinical-stage first-in-class small molecule with demonstrated anticancer activity against aggressive refractory/recurrent glioblastoma multiforme (GBM) tumors in vitro, ex vivo, and in vivo. This novel compound imparts its antitumor effects through a unique mechanism of action that involves indirect dual inactivation of Akt and ERK in tumor but not normal cells. Several academic investigators at premier institutions have demonstrated the optimal preclinical profile of ONC201 in a multitude of models. These findings have prompted Oncoceutics to rapidly translate this product into the clinic to treat advanced cancer patients. The first-in-man trial is a phase I/II study that will include patients with GBM is scheduled to begin in early 2014 at MGH and has been reviewed by the FDA as part of the accepted IND. Following completion of the dose-escalation phase I portion of the trial supported by Oncoceutics, the phase II trial can begin to evaluate the monoagent efficacy of ONC201 in patients with advanced GBM. In this fast-track application, we propose to develop an automated manufacturing process to provide the clinical supply of drug product followed by evaluation of the clinical efficacy of the resulting product in patients with GBM. Phase/Aim #1: Optimize ONC201 formulation and produce GMP product for GBM trial; Phase/Aim #2: Evaluate clinical efficacy of oral ONC201 in GBM. These studies will enable a development path for ONC201 to treat GBM, which is otherwise unattainable based on investor feedback that indicates a clear need for pilot clinical data in the indication to enable private support. This proposal seeks to make a novel anticancer agent available to patients in dire need of treatment options, will push the product toward commercialization, sufficiently derisk private investments to enable subsequent development, and will advance the field forward by enabling clinical evaluation of a novel therapeutic mechanism.