Clinical Trials

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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/29/2024. Questions regarding updates should be directed to the study team contact.