Mirdametinib + Radiotherapy for Brain Tumors

(NF118 Trial)

This trial aims to evaluate the effectiveness of mirdametinib, an experimental drug, alone or with radiation, in treating specific brain tumors. The focus is on participants with glioblastoma or other high-grade gliomas, particularly those with the genetic condition NF1. It includes individuals with recurrent or newly diagnosed tumors and tests various treatment combinations. Those with recurrent glioblastoma or newly diagnosed NF1-related tumors may qualify. Participants must not have recently received certain other treatments and should manage daily symptoms or side effects effectively. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in brain tumor therapies.

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use any prohibited medications, including certain herbal supplements or foods, within 7 days before starting the study treatment. It's best to discuss your current medications with the study team.

Research has shown that mirdametinib is generally safe for people. In earlier studies, patients with neurofibromatosis type 1 (NF1) who took mirdametinib experienced some side effects, but most were manageable. Common side effects included rash, diarrhea, and nausea.

Another study found that 43% of patients continued treatment without major problems, although a few stopped due to side effects or worsening conditions. Mirdametinib has also been used safely in children with low-grade brain tumors, demonstrating its effectiveness and safety for young patients.

Researchers are excited about mirdametinib for brain tumors because it targets a key pathway involved in tumor growth called the MEK pathway, which is different from the standard treatments like surgery, radiation, and chemotherapy. Mirdametinib offers a targeted approach, potentially leading to fewer side effects compared to traditional chemotherapy, which affects both cancerous and healthy cells. Additionally, when combined with radiotherapy, as explored in certain cohorts, it may enhance the treatment's effectiveness by making tumors more sensitive to radiation. For certain participants, mirdametinib is being explored as a standalone therapy, which could provide a less invasive treatment option.

Research shows promising results for mirdametinib, especially when combined with radiotherapy for brain tumors. In this trial, participants in Cohorts 1 and 2 will receive mirdametinib with radiation. Studies have found that mirdametinib has an 87% success rate in treating low-grade gliomas with certain genetic changes, suggesting it might also work for more aggressive tumors. For NF1-deficient glioblastoma, mirdametinib with radiation has made tumors more responsive to treatment. Participants in Cohort 3 will receive mirdametinib alone, which lab studies have shown to slow tumor growth. While research is ongoing, these findings suggest mirdametinib could be a helpful treatment option for certain brain tumors.³⁶⁷⁸⁹