In short
ONC206 is an investigational drug being studied in children and young adults with diffuse midline glioma (DMG) and other recurrent malignant brain tumours. The only registered trial is a Phase 1 study (NCT04732065) with a planned enrolment of 256 participants. The trial is currently authorised, meaning it is approved to start or is actively recruiting.
Key points
- Phase 1 trial in children and young adults with brain tumours
- Planned enrolment of 256 participants
- Studies ONC206 alone and in combination with radiation therapy
- Main goal is to find the maximum tolerated dose
- Also measures whether the drug crosses the blood-brain barrier
- Trial status: Authorised
What is ONC206?
ONC206 is the short name for the chemical substance 4-((2,4-difluorophenyl)methyl)2,4,6,7,8,9-hexahydro-7(phenylmethyl)imidazo(1,2-a)pyrido(3,4-e)pyrimidin-5(1H)-one. It is an investigational drug, meaning it is not yet authorised as a medicine. In the registry data, it is described as a chemically synthesised substance that is being tested in oncology, specifically in brain tumours.
The substance is given orally as a powder in the clinical trial. It is being studied in children and young adults with newly diagnosed or recurrent diffuse midline glioma (DMG) and other recurrent primary malignant central nervous system (CNS) tumours.
How does ONC206 work?
The trial data do not describe the mechanism of action of ONC206 in detail. One of the main goals of the trial is to determine whether the drug passes the blood-brain barrier and enters the tumour tissue. The blood-brain barrier is a protective layer that stops many substances from reaching the brain. Measuring drug levels in tumour tissue and comparing them to levels in the blood is part of the target validation in this study.
Which conditions is ONC206 being studied for?
- Diffuse midline glioma (DMG), H3K27 altered — a type of brain tumour that occurs mainly in children and young adults, often in the thalamus or pons. The trial studies ONC206 in newly diagnosed patients and in those whose disease has progressed.
- Other recurrent primary malignant central nervous system (CNS) tumours — brain tumours that have come back after previous treatment.
How is ONC206 given?
ONC206 is given orally as a powder. The trial tests it as a single agent and in combination with focal radiation therapy or re-irradiation.
What do the clinical trials show?
One registered clinical trial is available. It is a Phase 1, open-label study (NCT04732065) with a planned enrolment of 256 children and young adults. The trial is currently authorised. Phase 1 means the main purpose is to find the maximum tolerated dose (MTD) and to gather first information about safety.
The study has two parts. In the dose escalation and expansion part, ONC206 is tested as a single agent in patients who have completed at least one prior line of therapy including focal radiation, and in patients with recurrent primary malignant CNS tumours. It is also tested in combination with focal radiation in newly diagnosed patients and in combination with re-irradiation in patients whose DMG has progressed. The main measure is the maximum tolerated dose within the first 4 weeks of treatment, or during radiation for the combination arms.
In the target validation part, the trial measures the concentration of ONC206 in tumour tissue and compares it to drug levels in the blood before surgery. This is done in patients with DMG located in the thalamus, in the pons, and in other locations, as well as in patients with recurrent primary malignant CNS tumours.
What side effects are known?
The available trial data do not list specific side effects for ONC206. As a Phase 1 study, one of the main goals is to find the maximum tolerated dose and to observe what side effects occur. No side effect information from supplementary sources is available for this page.