A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy in Children and Young Adults With High-grade Glioma Following Radiotherapy

A Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib in Combination With Temozolomide Compared to Temozolomide Monotherapy in Children and Young Adults With Newly Diagnosed High-Grade Glioma Following Radiotherapy

The purpose of this study is to measure the benefit of adding abemaciclib to the chemotherapy, temozolomide, for newly diagnosed high-grade glioma following radiotherapy.

Your participation could last approximately 11 months and possibly longer depending upon how you and your tumor respond.

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.