Inclusion Criteria:
* 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.
Exclusion Criteria:
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.
