Children's National

• Biopsy proven high-grade glioma (HGG) as defined by 2016 World Health Organization (WHO) Classification Criteria, Grade 3-4 including: - Anaplastic astrocytoma - Anaplastic ganglioglioma - Anaplastic oligodendroglioma. - Anaplastic pleomorphic xanthoastrocytoma, - Glioblastoma OR as defined by the 2021 WHO Classification Criteria as molecularly characterized: - Non-pontine diffuse midline glioma, H3 K27-altered, - Diffuse hemispheric glioma, H3 G34-mutant - Diffuse pediatric HGG, H3/IDH-wildtype - Infant-type hemispheric glioma - High-grade astrocytoma with piloid features - High-grade pleomorphic xanthoastrocytoma - IDH-mutant diffuse glioma with homozygous cyclin- dependent kinase inhibitor 2A/B (CDKN2A/B) deletion, - IDH-mutant and 1p/19q co-deleted oligodendroglioma - IDH-mutant astrocytoma with homozygous CDKN2A/B deletion - Contraceptive use should be consistent with local regulations for participants in clinical studies. - Radiotherapy initiated within 6 weeks (+1 week) of diagnosis and administered over 6 weeks (±1 week). Participants <3 years of age, considered not suitable for radiotherapy may be eligible. - Minimum of 4 weeks between completion of radiation and Cycle 1 Day 1 (C1D1). - Maximum of 8 weeks between completion of radiation and C1D1. Exceptional circumstances can be discussed with the medical monitor. - Acute effects of prior therapies must be Grade ≤1 unless deemed clinically insignificant by the investigator. - Adequate hematologic and organ function ≤7 days prior to C1D1 - Life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment. - A performance score of ≥60 using: 1. Lansky scale for participants <16 years 2. Karnofsky scale for participants ≥16 years - Able to swallow and/or have a gastric/nasogastric tube. - Any current systemic steroid use dose must be stable or decreasing at least 7 days prior to C1D1. - Able and willing to adhere to study procedures, including frequent blood draws and MRI. - At least 28 days since any major surgery, laparoscopic procedure, or a significant traumatic injury. - Has a body surface area (BSA) of ≥0.2 m2.

Participants are excluded if any of the following apply: - Diffuse Intrinsic Pontine Glioma (DIPG) or diffuse midline glioma located in the pons. - Recurrent or refractory HGG including any recurrence/progression during/after radiotherapy. - Secondary HGG, defined as a previously treated low-grade glioma that now meets high- grade criteria, or that resulted from a previously treated malignancy. - Have known pathogenic somatic mutations appropriate for an anaplastic lymphoma kinase (ALK), B-rapidly accelerated fibrosarcoma (BRAF), or neurotrophic tyrosine receptor kinase (NTRK ) inhibitor, in regions where these therapies are available and deemed appropriate by the investigator. - Prior HGG treatment (including bevacizumab), except for surgery and radiotherapy (with or without concomitant temozolomide). - Current enrollment in another trial deemed incompatible with this study. - Treatment with an investigational product within the last 30 days or 5 half-lives (whichever is longer). - Prior malignancy within the previous 3 years that, per the investigator and the medical monitor, may affect interpretation of study results. - A preexisting medical condition(s) that, per the investigator, would preclude study participation. - Any serious, active, systemic infection requiring IV antibiotic, antifungal, or antiviral therapy, including acute hepatitis B or C, or Human Immunodeficiency Virus at C1D1. - Intolerability or hypersensitivity such as urticaria, anaphylaxis, toxic necrolysis, and/or Stevens-Johnson syndrome to temozolomide, and/or abemaciclib, their excipients, or dacarbazine. - Received a live virus vaccine within 28 days of C1D1. - Pregnant, breastfeeding, or intend to become pregnant during the study.