Phase 2 Study of ONC201-Based Combination Treatments for Children and Young Adults Aged 2 to 39 With Diffuse Midline Gliomas at Diagnosis, After Radiation, or at Progression

What this Trial Is About

Researchers are evaluating if combining ONC201 with various drugs is effective for treating children and young adults aged 2 to 39 years with diffuse midline gliomas DMGs, including diffuse intrinsic pontine gliomas DIPGs. The study uses an adaptive platform design with multiple cohorts based on disease stage newly diagnosed, post-radiation without progression, and progression stages. Novel agents may be added based on emerging preclinical data, and some cohorts include repeated intratumor infusions of DNX-2401. This is a phase II, open-label, multi-arm trial sponsored by the University of California, San Francisco. Treatment varies by cohort and includes oral ONC201 and paxalisib, radiation or re-irradiation therapy, and intratumoral DNX-2401 infusions given through a specialized cannula. Some participants may receive ONC201 as a safety lead-in before standard biopsy or radiation. Cycles repeat every 28 days in maintenance phases when no unacceptable side effects occur. Cohorts differ by timing related to radiation therapy and molecular tumor characteristics, with some participants receiving combination targeted therapies based on tumor or cerebrospinal fluid molecular profiles. Participants undergo assessments including tumor tissue collection, imaging, and laboratory tests. They are monitored for progression-free survival, overall survival, safety, and drug dosing effects. Follow-up visits occur at 30 days post-treatment and then every 3 months for up to 5 years or until withdrawal or death. Researchers also evaluate biomarkers, pharmacokinetics, immune cell changes, and quality of life measures. The study duration extends until June 2029, with primary completion expected by the end of 2027.

Combination Therapy for the Treatment of Diffuse Midline Gliomas