ONC201 In Brain And Other CNS Tumors

The development of ONC201 is focused on treating brain tumors with H3 K27M mutations. This focus is based on both preclinical and clinical results that have shown the ability of single agent ONC201 to address this disease. For more information about clinical trials of ONC201 in other cancer indications, please refer to our clinical trial summary page.


Neuro-oncology is a category that includes all tumors of the brain and spinal cord, such as astrocytoma, glioma, ependymoma, and glioblastoma. Gliomas are tumors which arise from glial cells, forming the tissue that surrounds and protects other nerve cells found within the brain and spinal cord. The term H3 K27M refers to a specific mutation in genes that encode for proteins called histone H3, which occurs in a subset of these tumors. While the mutation can be found in tumor locations across the nervous system and across age groups, H3 K27M has a higher occurrence in midline brain locations (thalamus, brainstem, spinal cord) and in younger patients. The mutation can occur in several different types of brain tumors, including astrocytoma, glioblastoma (GBM), and diffuse intrinsic pontine glioma (DIPG).

Tumors with this mutation have no effective treatments and are associated with poor overall survival. Standard treatment for many patients consists of radiation and, when feasible, surgery. Chemotherapy is not curative for any of these brain tumors and has proven ineffective in some types of high-grade gliomas, such as DIPG.


In our clinical trials and in compassionate use cases for ONC201, patients with H3 K27M mutations in different brain tumors, particularly diffuse intrinsic pontine glioma (DIPG), glioblastomas (GBM) and other high-grade midline tumors have shown promising results, including significant tumor shrinkage and other considerable clinical improvements.

ONC201 is uniquely suited to address brain tumors because of the drug’s rare ability to cross the blood brain barrier, allowing it to achieve therapeutic concentrations within the brain tumor. In prior clinical trials, ONC201 demonstrated that it is well-tolerated in patients. The drug antagonizes specific dopamine receptors that are highly expressed in tumors of the brain, particularly those that occur in its midline structures. By antagonizing these dopamine receptors in a unique way, ONC201 selectively shuts off cancer signaling pathways that are supporting tumor growth. This can stop the cancer from growing and induce tumor cell death that leads to tumor shrinkage and often other clinical improvements. Please refer the ‘Our Science’ section of our website for more information about how ONC201 acts on the dopamine receptor to control cancer.


Dr. Minesh Mehta is a renowned expert in radiation oncology, proton therapy and neuro-oncology research at the Miami Cancer Institute. In the video below, he speaks about the challenges in treating patients with glioblastoma and other neuro-oncology indications and highlights the potential of ONC201 to address this devastating set of diseases.


Dr. Isabel Arrillaga-Romany is a neuro-oncologist at the Massachusetts General Hospital and leads an ongoing clinical trial of ONC201 in GBM (NCT02525692). In this video, she speaks about the early results seen in her study, specifically the results seen in a patient with a H3 K27M glioma.