I3Y-MC-JPEH: 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 primary objective of this study is to evaluate the clinical benefit of adding **abemaciclib** to the chemotherapy regimen of **temozolomide** in children and young adults with newly diagnosed high-grade **glioma** following radiotherapy. This investigation is clinically relevant as it aims to determine whether the combination therapy can improve outcomes compared to temozolomide monotherapy, potentially offering a more effective treatment option for this aggressive form of brain cancer.

The clinical trial involves a total of **22 participants** diagnosed with high-grade **glioma**. The study population includes both male and female subjects, with an age range starting from 3 years old. Participants have previously undergone radiotherapy, with or without temozolomide, and must have recovered from major side effects of prior treatments. They are required to have adequate organ function and blood counts, as determined by laboratory tests. The trial population was selected based on their ability to swallow or use a feeding tube, and their willingness and ability to adhere to study procedures, which include frequent laboratory tests and tumor imaging. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of all participants.

The clinical trial is designed as a **randomized**, open-label, Phase II study to evaluate the efficacy of **abemaciclib** in combination with **temozolomide** compared to temozolomide monotherapy in children and young adults with newly diagnosed high-grade **glioma** following radiotherapy. The trial aims to assess the benefit of adding abemaciclib to the chemotherapy regimen. The primary endpoint is event-free survival as determined by a blinded independent review committee. The trial is expected to commence recruitment on August 20, 2024, and conclude by May 12, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as having high-grade glioma, prior radiotherapy, and adequate organ function. Participants must be able to swallow or have a feeding tube and be willing to comply with study procedures. The trial involves frequent laboratory tests and tumor imaging to monitor the participants' health and response to treatment.

The expected duration of participant involvement is up to 12 months, with the possibility of early termination if significant adverse effects occur or if the participant withdraws consent. The study will include follow-up visits to assess the ongoing safety and efficacy of the treatment regimen. The end-of-study visit will evaluate the overall outcomes and any long-term effects of the treatment. Participants will be monitored closely throughout the trial to ensure their safety and the integrity of the study data.

The clinical trial involves the administration of **Temozolomide**, an antineoplastic agent of chemical origin, as part of the treatment regimen. Temozolomide is provided in a pharmaceutical form identified as PHF00005MIG, and is administered orally. The dosage is calculated based on body surface area, with a maximum daily dose of 200 mg/m² and a total maximum dose of 28,600 mg over a treatment period of up to 12 months. The administration schedule is designed to ensure optimal therapeutic efficacy while monitoring participant compliance through regular assessments.

**Abemaciclib** is another investigational agent used in this study, available in multiple pharmaceutical forms including film-coated tablets, granules, and standard tablets. The film-coated tablets, marketed as Verzenios 50 mg, are authorized under the marketing authorization number EU/1/18/1307/001. Abemaciclib is also of chemical origin and is administered orally. The maximum daily dose for Abemaciclib is 400 mg, with a treatment period limited to 1 month. The study utilizes different packaging and labeling for clinical trial purposes, distinct from the marketed product, to ensure compliance with trial protocols.

In this trial, Abemaciclib is evaluated both as a monotherapy and in combination with Temozolomide. The combination therapy aims to assess the potential benefit of adding Abemaciclib to the standard chemotherapy regimen for patients with newly diagnosed high-grade glioma following radiotherapy. Participant adherence to the dosing schedule is closely monitored to ensure accurate assessment of the treatment's efficacy and safety.

The efficacy of the clinical trial will be assessed primarily through the measurement of **Event Free Survival** as determined by a Blinded Independent Review Committee. This endpoint is designed to evaluate the benefit of adding abemaciclib to the chemotherapy regimen of temozolomide in children and young adults with newly diagnosed high-grade glioma following radiotherapy. The trial is structured as a randomized, open-label, Phase 2 study, comparing the combination therapy to temozolomide monotherapy.