Abstract Background Gliomas are the most common pediatric brain tumors, with approximately 30% being high-grade. With a 3-year event-free survival (EFS) rate of 15%, novel therapies for high-grade glioma (HGG) are urgently needed. Approximately one-third of pediatric HGGs contain CDK4/6 pathway alterations (Mackay et al., 2018), making CDK4/6 inhibitors rational candidates for clinical testing. Abemaciclib is a selective CDK4/6 inhibitor approved for treatment of breast cancer. Abemaciclib in combination with temozolomide (TMZ) was evaluated in pediatric and young adult patients with relapsed or refractory solid tumors, including brain tumors, in the Phase 1b/2 study, JPCS (NCT04238819). JPEH (NCT06413706) is evaluating abemaciclib + TMZ versus TMZ in pediatric and young adult patients with HGG. Methods JPEH is a randomized, open-label, Phase 2 study enrolling patients from birth to 21 years with newly-diagnosed HGG (based on WHO 2016 or 2021 classification) following radiotherapy. Approximately 45 patients will be randomized 2:1 to either abemaciclib + TMZ or TMZ and stratified by CDK4/6 pathway alteration (yes, no, or unknown). Arm A will receive oral abemaciclib (115 mg/m2) twice daily and IV or oral temozolomide (150 mg/m2) on Days 1-5 of 21-day cycles. Arm B will receive IV or oral temozolomide (150 mg/m2 in Cycle 1, 200 mg/m2 in Cycle 2+ if hematologic criteria are met) on Days 1-5 of 28-day cycles. Temozolomide treatment may continue for 1 year. Abemaciclib may continue until disease progression or other discontinuation criteria are met. The primary endpoint is EFS determined by a blinded independent review committee using Response Assessment in Pediatric Neuro-Oncology (RAPNO) for pediatric HGG. Key secondary endpoints include EFS determined by investigator assessment, overall survival, objective response rate, disease control rate, duration of response, and pharmacokinetics. Exploratory biomarker testing will be performed. JPEH is enrolling in Australia, Europe, Japan, and the United States.
Sales et al. (Fri,) studied this question.