Clinical Trial Finder

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.

• - Isocitrate dehydrogenase-mutant (IDH-mutant) 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 foe 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.

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, its excipients, or dacarbazine.

• - Received a live virus vaccine within 28 days of C1D1.

• - Pregnant, breastfeeding, or intend to become pregnant during the study.

Arms

Experimental: Abemaciclib + Temozolomide - Arm A

Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV).

Active Comparator: Temozolomide - Arm B

Participants will receive temozolomide administered orally or IV.

Interventions

Drug: - Abemaciclib

Administered orally

Drug: - Temozolomide

Administered orally or IV