Clinical efficacy of the antitumor agent ONC201 in GBM

抗肿瘤药物ONC201治疗GBM的临床疗效

基本信息

批准号：
9118605
负责人：
Wolfgang Oster
金额：
$ 84.75万
依托单位：
ONCOCEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9118605
关键词：
Advanced Malignant Neoplasm Adverse effects Animal Model Animals Antineoplastic Agents Apoptosis Authorization documentation Biological Markers Blood - brain barrier anatomy Brain Neoplasms Cancer Patient Canis familiaris Capital Caring Cell Line Cell model Cells Chemicals Clinic Clinical Clinical Data Clinical Protocols Clinical Trials Data Development Dose Drug Formulations Drug Targeting Drug usage Enrollment Ensure Evaluation Excipients Feedback Funding Future Genes Glioblastoma Health Human Image In Vitro Institution Investments Laboratories Libraries Ligands Malignant Neoplasms Medical Methods Modeling Mutate New Agents Newly Diagnosed Normal Cell Oral Patient Selection Patients Pharmaceutical Preparations Phase Phase II Clinical Trials Phosphotransferases Probability Process Property Radio Rattus Recurrence Refractory Reproducibility Research Personnel Resistance Safety Sampling Schedule Secure Serum Markers Staging TNFRSF10B gene TNFSF10 gene Testing Therapeutic Time Toxicology Translating Work anticancer activity antitumor agent antitumor effect arm base cancer cell capsule clinical efficacy commercialization improved in vivo killings man manufacturing process neoplastic cell novel novel therapeutics phase 1 study phase II trial pre-clinical receptor research clinical testing response screening small molecule success targeted treatment therapy resistant transcription factor tumor

项目摘要

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.

描述（由应用提供）：ONC201是一种临床阶段的第一类小分子，其在体外，Ex Vivo和Vivo中具有抗癌/复发性胶质母细胞瘤（GBM）肿瘤的抗癌活性。这种新颖的复合通过独特的作用机理赋予其抗肿瘤作用，该机制涉及肿瘤中Akt和ERK的间接双重失活，而不是正常细胞。总理机构的几位学术研究人员已经证明了ONC201在多种模型中的最佳临床前概况。这些发现促使Oncoutics迅速将该产品转化为诊所以治疗晚期癌症患者。人类的第一个试验是一项I/II期研究，该研究将包括GBM患者，计划于2014年初在MGH开始，并已由FDA作为接受IND的一部分进行了审查。在由Oncoutics支持的试验的I剂量I期完成后，II期试验可以开始评估晚期GBM患者ONC201的单一效率。在此快速应用中，我们建议开发自动制造过程，以提供药物的临床供应，然后评估GBM患者所得产品的临床效率。阶段/目标＃1：优化ONC201公式并生产GMP产品进行GBM试验；阶段/目标＃2：评估口服ONC201在GBM中的临床效率。这些研究将使ONC201治疗GBM的开发路径，这是基于投资者的反馈而无法获得的，这表明对试点临床数据的明确需求表明可以实现私人支持。该提案旨在使患者可以直接需要治疗选择，将产品推向商业化，充分挑战私人投资以实现后续开发，并通过对新型热机制进行临床评估，将产品推向商业化。