Dabrafenib and trametinib either in combination or as monotherapy in pediatric patients harboring BRAF alterations in gliomas or other rare tumors: Findings from a managed access program

<h2>Abstract</h2><h3>Background</h3> To enable global access to therapies in countries where suitable formulations and/or indications are not yet approved, managed access programs (MAPs) are established. Herein, we report patient data from a MAP for pediatric patients with <i>BRAF-</i>altered gliomas or other rare tumors, seeking clinical benefit from dabrafenib and/or trametinib. <h3>Methods</h3> We analyzed data from global MAP, where pediatric patients with <i>BRAF</i> alterations in gliomas or other rare tumors received dabrafenib and/or trametinib. Key eligibility criteria were age <18 years, absence of approved alternative therapies, presence of <i>BRAF</i> alterations, and exhausted standard therapies. Requests analyzed in this study were collected from April 2015 to December 2023 (cutoff date). The main objectives were to describe patients' characteristics and treatment duration. <h3>Results</h3> Overall, 863 patients with solid malignancies were included, of which 30.4%, 23.4%, and 46.2% received combination therapy, dabrafenib monotherapy and trametinib monotherapy, respectively. Median age was 6.4 years, and 51% were male. Most patients had low-grade (80.9%) or high-grade (5.6%) gliomas, followed by Langerhans' cell histiocytosis (13.6%). The median treatment duration (mDoT) was >12 months (ranged between 12.4 and 45.9 months) irrespective of the treatment groups, disease types, and formulations. At the data cutoff, treatment was ongoing for approximately 47% of patients. <h3>Conclusions</h3> MAP data are a valuable real-world resource for understanding patient characteristics in rare tumors such as pediatric gliomas. A significant number of treatment requests indicate substantial unmet need, and observed mDoT across subgroups suggests potential treatment benefit in these patients. No new safety findings were identified for dabrafenib/trametinib.