Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK

This study is looking for children and young people between the ages of 2 and 25 years old. To join, you must have been recently diagnosed with paediatric low-grade glioma, or your tumour hasn't been treated with other medicines or radiotherapy before. Importantly, your tumour needs to show a specific genetic change (called activation of the MAPK pathway, but not a BRAF V600E mutation) or be linked to conditions like neurofibromatosis type 1 (NF1) or have a specific KIAA1549-BRAF fusion.

There are also some general health requirements. You'll need to be well enough to take part, have certain body measurements, and your organs (like your heart and blood) need to be working properly as shown by tests. You must also be able to take medication by mouth. If you are able to have children, you and your doctor will need to discuss birth control methods.

Some things would mean you couldn't join. For example, if you're already receiving other experimental treatments, have a specific heart condition, another serious cancer, or a certain type of genetic change (BRAF V600E mutation) in your tumour. Also, if your blood pressure is too high for your age, or if you can't take medicines by mouth, you wouldn't be able to participate.

If you join this study, it will involve a few different stages. First, a small group of patients will help us find the right dose of the two medicines, mirdametinib and vinblastine, that works best and is safe. This involves carefully increasing the dose within safe limits until the best combination is found.

You would take mirdametinib by mouth twice a day, every day, for about a year (13 cycles, with each cycle lasting 28 days). The vinblastine would be given through a vein once a week for a longer period, around 17 cycles. The dose of vinblastine will be adjusted based on what is found to be the safest and most effective for everyone. If you experience side effects, the doctors might reduce the dose of your medication.

Throughout the study, you'll have regular hospital visits for check-ups, blood tests, and scans (like an MRI with contrast) to see how you're responding to the treatment and to monitor for any side effects. After your treatment finishes, you'll continue to have follow-up visits every six months for three years to see how you're doing in the longer term. In total, we plan for 50 patients to take part in this study.