On November 13, 2019 Oncoceutics, Inc. reported that results from the second and third cohort of the Phase II trial for patients with recurrent glioblastoma treated with the company’s lead imipridone, ONC201, were recently published in the journal Neuro-Oncology (Press release, Oncoceutics, NOV 13, 2019, View Source [SID1234558331]). This manuscript represents the third publication among a series of reports demonstrating durable radiographic regressions with ONC201 in patients with H3 K27M-mutant glioma. The study (NCT02525692) also demonstrated that weekly oral administration of ONC201 given as a single agent was well-tolerated, achieved therapeutic intratumoral concentrations, and intratumoral pharmacodynamic activity in adult recurrent glioblastoma patients.
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ONC201 achieved intratumoral concentrations that exceeded preclinical efficacy thresholds and induced intratumoral biomarkers of pharmacodynamic signaling and apoptosis indicating target engagement. The radiographic regression of multi-focal, multi-recurrent disease with ONC201 administration in an adult recurrent H3 K27M-mutant glioblastoma patient remained durable for >1.5 years. No treatment modifications or discontinuations due to toxicity were observed, including those who underwent re-resection.
A previous publication on the first cohort of the study had demonstrated that ONC201 is well-tolerated in adult recurrent glioblastoma patients with every three-week dosing and achieved an objective radiographic response in a patient harboring the H3 K27M mutation that remained durable for >2.5 years. Other publications have reported radiographic regressions and clinical benefit in pediatric and adult H3 K27M-mutant diffuse midline glioma patients including those with diffuse intrinsic pontine glioma (DIPG).
High-grade glioma with the H3 K27M mutation is the lead indication for ONC201 and FDA has awarded Fast-Track designation to ONC201 for the treatment of adults with this disease who have recurred. The publication is supported by Small Business Innovation Research (SBIR) Fast-track and Bridge grants from the National Cancer Institute of the National Institutes of Health, as well as The Musella Foundation.
"These results indicate weekly ONC201 is very well tolerated and biologically active in a molecular subset of glioblastoma patients associated with biomarkers of dopamine receptor dysregulation," said Isabel Arrillaga-Romany, MD, PhD, Director of Neuro-Oncology Clinical Trials at Massachusetts General Hospital and the Principal Investigator and corresponding author of the study. "The durable regression observed in a 74-year old patient with sub-centimeter multi-focal, multi-recurrent H3 K27M-mutant glioma is particularly noteworthy given the development focus of ONC201 in this subset of brain tumors."
"Overall, the safety and efficacy results with ONC201 in recurrent glioblastoma are promising and unlike any other targeted agent we have evaluated thus far," said Patrick Y. Wen, MD, Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and senior author and investigator of the study. "ONC201 continues to be promising as a single agent in molecular subsets of high-grade glioma and the intratumoral pharmacodynamic results suggest the activity of ONC201 may extend beyond H3 K27M-mutant gliomas to high-grade glioma subsets that also exhibit dopamine pathway dysregulation."