Adastra Pharmaceuticals Announces Positive Top-Line Data from Phase 1b Clinical Trial of Zotiraciclib in the Treatment of Recurrent High-grade Gliomas


2021-01-13 23:14:22 BioSpace


 Adastra Pharmaceuticals, Inc., a biopharmaceutical company focused on the development of first-in-class therapeutics for the treatment of cancer, today announced the completion of the Phase 1b clinical trial conducted by the NCI with its lead clinical candidate zotiraciclib , a potent oral cyclin-dependent kinase 9 inhibitor. The trial investigated the safety and efficacy of ZTR, in combination with temozolomide , in patients with recurrent high-grade gliomas. The Phase 1b trial exceeded or met the prespecified trial endpoint of progression-free survival (PFS) and provided a recommended dosing of ZTR. In the subset of patients who had isocitrate dehydrogenase (IDH) mutated tumors, the combined treatment with ZTR and temozolomide conferred a profound benefit of mPFS over historical control. The study additionally found ZTR to be well tolerated. The trial was sponsored and conducted by the NCI, and NCI expects to publish and report its findings and present them at an upcoming medical conference in 2021. "Because preclinical data demonstrated the ability of ZTR to inhibit CDK9, enhance apoptosis and cause mitochondrial dysfunction and ultimately ATP depletion in glioma cells, we were optimistic about this first-in-human glioma trial," said Jing Wu, M.D., Ph.D., NCI's Principal Investigator of the 17-C-0009 trial. "The data from the Phase 1b trial support our initial expectations and reinforce our energies to continue to investigate ZTR as a treatment for patients with gliomas." "We are very grateful to our NCI colleagues, the patients, and their families for their participation in this trial. Recurrent high-grade gliomas are aggressive malignant brain tumors and remain difficult cancers to treat. Currently, available agents used for the treatment of gliomas offer little or no proven benefit; new therapeutic options are needed," said Scott Megaffin, Chief Executive Officer of Adastra. "We are exceptionally encouraged by the potential of zotiraciclib as a new treatment alternative for patients with recurrent high-grade gliomas. On the basis of these findings, Adastra is in active preparation of a registration-enabling clinical study of ZTR in patients with recurrent high-grade gliomas, in addition to work now underway to expand the application of ZTR to additional solid tumors and hematologic malignancies." The majority of glioblastoma multiforme (GBM) cases are recurrent, and the mortality rate for patients with recurrent gliomas is nearly 100%, representing a significant unmet medical need. Furthermore, currently approved treatment options for recurrent, high-grade gliomas have limited effectiveness, creating the need for medicines like ZTR, which possesses a unique mechanism of action. ZTR is a potent oral CDK9 inhibitor with the ability to readily cross the blood-brain barrier and deplete short-lived proteins like Mcl-1 and Myc, known antiapoptotic oncogenes. About Adastra Pharmaceuticals Adastra Pharmaceuticals Inc. is an innovative, private, clinical-stage biopharmaceutical company committed to providing responsible solutions to advance patient care in oncology. Our vision is to identify, develop and deliver to patients important new therapies for diseases with significant unmet need. This commitment is epitomized by our lead clinical candidate, zotiraciclib (ZTR), which is initially being developed for the treatment of high-grade gliomas (HGG) and diffuse intrinsic pontine glioma (DIPG), two forms of brain cancer characterized by Myc overexpression. ZTR has been granted Orphan Drug designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of gliomas. Adastra possesses a rich history of institutional and academic collaboration, including ongoing clinical research programs with the National Cancer Institute (NCI) and the European Organisation for Research and Treatment of Cancer (EORTC). We invite you to learn more about Adastra, our clinical and scientific partners and our journey to bring meaningful new therapies to patients, by visiting Media Contacts: Ignacio Guerrero-Ros, Ph.D. Russo Partners, LLC (646) 942-5604 David Melamed, Ph.D. Russo Partners, LLC (212) 845-4225 multimedia:
Inc.的Adastra Pharmaceuticals公司是一家专注于开发治疗癌症的一流疗法的生物制药公司,今天宣布完成由NCI进行的1B期临床试验,其主要临床候选药物zotiraciclib是一种有效的口服细胞周期素依赖性激酶9抑制剂。该试验研究了ZTR联合替莫唑胺治疗复发性高级别胶质瘤的安全性和有效性。 1B期试验超过或达到了预定的无进展生存期(PFS)试验终点,并提供了推荐的ZTR剂量。在异柠檬酸脱氢酶(IDH)突变肿瘤患者中,ZTR和替莫唑胺的联合治疗使mPFS比历史对照有更大的获益。研究还发现ZTR具有良好的耐受性。这项试验是由NCI赞助和进行的,NCI预计将公布和报告其研究结果,并在即将于2021年召开的医学会议上进行展示。 NCI 17-C-0009试验的首席研究员吴静博士(音译)说:“由于临床前数据显示ZTR有能力抑制CDK9,增强细胞凋亡并导致线粒体功能障碍,最终导致胶质瘤细胞ATP耗尽,我们对这一首次人类胶质瘤试验感到乐观。”1B期试验的数据支持了我们最初的预期,并加强了我们继续研究ZTR作为胶质瘤患者治疗方法的精力。“ Adastra公司首席执行官Scott Megaffin说:“我们非常感谢NCI的同事,患者和他们的家人参与这项试验。复发性高级别胶质瘤是恶性脑肿瘤,仍然是难以治疗的癌症。目前,用于治疗胶质瘤的现有药物提供很少或没有被证实的益处;需要新的治疗选择。”zotiraciclib作为复发性高级别胶质瘤患者新的治疗替代方案的潜力使我们倍受鼓舞。在这些发现的基础上,Adastra正在积极准备一项ZTR在复发性高级别胶质瘤患者中的可注册的临床研究,此外,目前正在开展的工作是将ZTR应用于其他实体瘤和血液系统恶性肿瘤。“ 多形性胶质母细胞瘤(GBM)的大多数病例是复发性的,复发性胶质瘤患者的死亡率接近100%,代表着一个显著的未满足的医疗需求。此外,目前已获批准的治疗复发性高级别胶质瘤的方法效果有限,这就需要ZTR这样的药物,它具有独特的作用机制。ZTR是一种强效的口服CDK9抑制剂,能够轻易地穿越血脑屏障,耗尽已知的抗凋亡癌基因Mcl-1和Myc等短命蛋白。 关于Adastra制药公司 Adastra制药公司是一家创新的,私营的,临床阶段的生物制药公司,致力于提供负责任的解决方案,以提高肿瘤患者的护理水平。我们的愿景是确定,开发和向患者提供重要的新疗法,以治疗那些有重大未满足需求的疾病。我们的主要临床候选药物佐替西利(zotiraciclib,ZTR)就是这种承诺的缩影,它最初被开发用于治疗高级别胶质瘤(high-grade gliomas,HGG)和弥漫性固有性脑桥胶质瘤(difuse intrinic pontine glioma,DIPG),这两种以Myc过度表达为特征的脑癌。ZTR已被美国食品药品管理局(FDA)和欧洲药品管理局(EMA)授予孤儿药的称号,用于治疗脑胶质瘤。Adastra拥有丰富的机构和学术合作历史,包括与美国国家癌症研究所(NCI)和欧洲癌症研究与治疗组织(EORTC)正在进行的临床研究项目。我们邀请您访问,更多地了解Adastra,我们的临床和科学合作伙伴,以及我们为患者带来有意义的新疗法的旅程。 媒体联系人: Ignacio Guerrero-Ros,博士。 Russo Partners有限责任公司 (646)942-5604 电子邮件 David Melamed博士。 Russo Partners有限责任公司 (212)845-4225 电子邮件 多媒体: