On April 24, 2020 Oncoceutics reported that Accelerate Brain Cancer Cure (ABC2) has awarded a $116,523 grant to a research team at University of California, Los Angeles to perform a natural disease history study of adult midline gliomas, a certain type of aggressive brain tumors (Press release, Oncoceutics, APR 24, 2019, View Source [SID1234558358]). The study will follow patients from first diagnosis through a series of therapeutic interventions that for a subset of patients will include ONC201, an investigational agent in clinical trials for H3 K27M-mutant gliomas that has induced radiographic regressions in some patients.
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"Novel therapies are desperately needed for treatment of H3 K27M-mutant gliomas," said Max Wallace, Chief Executive Officer of ABC2. "A dedicated natural history study will open up the path to accelerated approval based on radiographic responses to new treatments such as ONC201 in this rare and immediately life-threatening disease."
ONC201 is the first antagonist of D2-like dopamine receptors DRD2/3 to be developed for clinical neuro-oncology. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ONC201 for the treatment of adult recurrent H3 K27M-mutant high-grade glioma. Diffuse midline gliomas harboring the histone H3 K27M mutation have a dismal prognosis with a median survival from diagnosis consistently reported to be between 8 and 11 months. The mutation was chosen by the World Health Organization (WHO) as a criterion for WHO grade IV designation, the most severe grade that is associated with a diffuse and aggressive growth pattern. No drug has been approved for H3 K27M-mutant glioma and no investigational therapy has shown clinically meaningful efficacy in this indication. Radiation is typically used in newly diagnosed patients and associated with some benefit before the tumor progresses, leading to the dismal survival rates.
Despite the increased awareness for the prognostic importance of the H3 K27M mutation, dedicated studies of midline gliomas are sparse, particularly in adults. Response criteria that are often applied, e.g. RANO criteria, were developed for supratentorial glioblastoma that have different radiographic features than midline gliomas, including H3 K27M-mutant gliomas. Consequently, the utility of these criteria for many midline glioma patients are confounded by a number of features often found in this disease: minimal or no contrast enhancement, diffuse growth, multifocal dissemination, and sub-centimeter lesions (not measurable as per some criteria). With the disease classifications that consider phenotypic as well as genotypic disease characteristics (e.g. WHO 2016) and patient registries that collect historical data the disease can be studied in more detail. However, many features of midline gliomas are still poorly understood, including tumor growth rates, dissemination patterns, response to therapies, and the relationship of clinical outcomes to these features.
"The goal of the study is to quantify the dynamics of how midline gliomas change over time on clinical imaging to better understand the natural progression of this disease and if treatments can alter those dynamics," said Timothy F. Cloughesy, MD, Clinical Professor and Director of the Neuro-Oncology Program at the University of California, Los Angeles. "The natural disease history could serve as a benchmark for new therapies such as ONC201 and other agents targeting glioma. We are very thankful to ABC2 for their support that will allow us to research this important and unaddressed topic."