CTNI-22. DABRAFENIB (D) AND TRAMETINIB (T) EITHER IN COMBINATION OR AS MONOTHERAPY IN PEDIATRIC PATIENTS HARBORING<i>BRAF</i> ALTERATIONS IN GLIOMAS OR OTHER RARE TUMORS: FINDINGS FROM AN EARLY ACCESS PROGRAM (EAP)

Abstract BACKGROUND In 2022, dabrafenib and trametinib (D+T) combination received an accelerated US FDA approval for use in adult and pediatric patients with BRAF V600E–mutated unresectable or metastatic solid tumors with no viable alternative therapy. However, to provide global access to therapy in countries where the suitable formulations and/or indications are not yet approved, EAPs are established. We report on patient data from an EAP for pediatric patients with BRAF V600-mutated gliomas or other rare tumors with BRAF alterations such as BRAF fusions, seeking clinical benefit from therapy with dabrafenib and/or trametinib. METHODS We analyzed data from the global EAP, where pediatric patients with BRAF alterations in solid tumors including gliomas or other rare tumors received D+T combination or monotherapy. Key eligibility criteria included: age &amp;lt;18 years, absence of approved indications, presence of BRAF V600E/K mutation or other BRAF alterations, and exhaustion of standard therapies. Requests were processed through a global system from November 2016 to December 12, 2022 (cutoff date). Key data on patient characteristics and median treatment duration (mDoT) were collected and will be presented. RESULTS Overall, 482 patients with solid or hematological malignancies were included, of which 35.1%, 31.7%, and 33.2% received combination therapy and dabrafenib and trametinib monotherapies, respectively. Across the treatment cohorts, median age was 4.2-6.6 years, and 49.4%-52.9% were males. Most patients had low-grade (72%) or high-grade (4.6%) gliomas, followed by Langerhans cell histiocytosis (17.8%) and other tumors (5.6%). The estimated mDoT for liquid and solid formulations were, respectively, 14.6 months and 10.1 months in combination therapy, 16.5 months and 12.8 months in dabrafenib monotherapy, and 8.8 months and 7.4 months in trametinib monotherapy. CONCLUSIONS EAP data represent a valuable real-world resource in understanding patient characteristics in rare tumors (pediatric gliomas). A significant number of treatment requests indicate substantial unmet need, and significant mDoT across age categories was suggestive of benefit to pediatric patients on therapy.