On January 31, 2018 Oncoceutics, Inc. reported that the first patient has been treated in a clinical trial of ONC201 for pediatric patients with brain tumors that contain a specific mutation called the histone H3 K27M mutation (Press release, Oncoceutics, JAN 31, 2018, View Source [SID1234558373]). The trial, which will treat patients with recurrent high-grade gliomas, including glioblastoma and diffuse intrinsic pontine glioma (DIPG), is led by Sharon Gardner, MD, a pediatric neuro-oncologist at NYU Langone Health’s Stephen D. Hassenfeld Children’s Center for Cancer & Blood Disorders. The study will enroll approximately 45 pediatric patients using ONC201 as a single agent or in combination with radiotherapy for patients with recurrent or newly diagnosed disease, respectively.
The H3 K27M mutation has been identified as an important prognostic indicator in aggressive midline gliomas that involve specific parts of the brain, including the thalamus, pons, or spinal cord. In 2016, the World Health Organization categorized any midline brain tumor that contains the H3 K27M mutation as the highest grade (IV) because the mutation confers such a poor prognosis. Beyond palliative radiation, no medical therapy has been shown to provide clinical benefit for patients with this mutation in their tumor. Pediatric patients are particularly impacted by this mutation, especially those with DIPG where 70-80% of the patients have the mutation.
As previously announced, the company’s focus on H3 K27M mutual gliomas arose from success with a patient in the first group of its phase II trial for recurrent glioblastoma conducted at Harvard. This patient, a 22-year old woman, had the H3 K27M mutation and has experienced a 96% reduction in tumor size. She remains on therapy today (after 22 months) and has returned to her normal activities. Based on the strong result for this patient, Oncoceutics enrolled additional brain tumor patients with the H3 K27M mutation, and some of these patients have also done well, including a patient whose tumors have completely disappeared. In addition to enrolling more adult patients with the H3 K27M mutation at Harvard (where the trial was limited to adults), we have enrolled a handful of children with brain tumors that have the mutation under compassionate use protocols, special permission from the FDA to enroll patients on a case-by-case when there is no approved clinical trial accessible to the patient. We have also seen signs of efficacy in these children. In total, 14 patients with brain tumors that have the H3 K27M mutation have been treated with single agent ONC201 (7 in formal clinical studies and 7 in compassionate use studies), and five of these patients have demonstrated clinical and/or radiographic benefit from ONC201 therapy. These data will be reported in upcoming scientific conferences and publications. In addition, corroborating preclinical efficacy and mechanistic studies from the lab of Andrew Chi, MD, also at NYU Langone Health, have shown that H3 K27M gliomas cells are extremely sensitive to ONC201.
"The previously reported responses to ONC201 in patients with H3 K27M gliomas, combined with the preclinical results from Dr. Chi’s lab here at NYU, make me excited to offer ONC201 to our patients with this molecularly-defined disease," said Dr. Gardner. "To date, no drugs have proven effective in these tumors, and this patient population is in need of novel therapeutic options.
"We are excited to expand our existing clinical program targeted at patients with the H3 K27M mutation to the pediatric populations," said Lee Schalop, MD, Chief Operating Officer at Oncoceutics. "Based on the results we have seen in patients with the H3 K27M tumor mutation who have received ONC201, as well as the preclinical data generated by Dr. Chi, we believe that ONC201 offers a unique opportunity to eliminate these devastating tumors."