Generously funded by Donors of Brain Tumour Foundation of Canada

Julie Bennett – Hospital for Sick Children (SickKids) – Toronto, Ont.

Project title: “Understanding outcomes in pediatric patients treated with IDH inhibitors—A pilot cohort”

Description of project:

Gliomas are the most common type of brain tumour in children, adolescents and young adults. An IDH mutation is a genetic change that can lead to glioma formation. IDH-mutant glioma is typically found in young adults, with these tumours universally progressing over time. Historically, treatment included observation for low-grade IDH-mutant glioma and radiation and chemotherapy when treatment was required. Improved outcomes were observed in a recent trial for patients treated with Vorasidenib, an oral IDH inhibitor. IDH­mutant glioma can rarely occur in adolescents. Vorasidenib is approved for patients >12 years old, but no patients under the age of 18 received Vorasidenib in the trial, so there is limited data on tumour response and side effects in adolescents.

We propose to study a pilot cohort of teenage patients with IDH-mutant glioma on Vorasidenib. The primary goal is to measure progression-free survival, while secondary objectives include assessing tumour response, identifying biomarkers to predict outcomes, and documenting toxicity. The study will explore characteristics in the tumour and cerebrospinal fluid that may provide additional insights unique to younger patients. This multicenter pilot study will provide crucial data on the use of Vorasidenib in adolescents, influencing treatment strategies for IDH-mutant gliomas worldwide.

What receiving this award means:

Winning a grant from Brain Tumour Foundation of Canada provides crucial support to study a pilot cohort of pediatric patients with IDH-mutant glioma. With the recent FDA and Health Canada approval of an IDH-inhibitor, Vorasidenib, which has shown promising results in treating IDH-mutant glioma in adults, we hope to better understand the impact of this drug in pediatric patients. This grant allows our team to investigate a promising therapeutic approach and its impact on this understudied population. It not only validates the importance of this research but also fuels my commitment to improving outcomes for children facing these types of brain tumours. The opportunity to contribute to advancing scientific knowledge and potentially shaping future treatment strategies for pediatric IDH-mutant glioma patients is both humbling and inspiring.

Update – December 2025

To date, 10 adolescent patients with IDH-mutant glioma who are being treated with Vorasidenib have been enrolled and are under active monitoring (8 Canadian, 2 international). Patients are being followed with serial liquid biopsies to assess disease evolution. Findings highlight key differences in toxicity profiles between adolescents and the published adult cohorts in the INDIGO trial. We have also observed a similar reduction in tumour growth velocity in adolescent patients after initiating Vorasidenib, consistent with findings from INDIGO. Among patients treated with Vorasidenib, the majority presented with radiographic disease stability or improvement on serial MRI; several demonstrated stunted tumour growth or a small radiographic response. Treatment is generally well tolerated; hepatotoxicity was the most common adverse event, managed through reducing the dose. The differences in toxicity have prompted the development of a follow-up study, focusing on pharmacokinetics in adolescent patients to directly compare with adult INDIGO data. This work will inform future treatment strategies and optimize dosing for younger patients. An abstract outlining the rationale and preliminary observations will be submitted for presentation at ISPNO 2026 in Sydney, Australia.

We plan to further annotate tumour samples from the adolescent cohort to evaluate potential biological differences compared to adult IDH-mutant glioma. Additional ongoing work includes volumetric imaging analyses to assess treatment response and continued monitoring for emerging toxicities.