ANHL2121: Phase 2 Study of Tovorafenib (DAY101) in Relapsed and Refractory Langerhans Cell Histiocytosis

Recent discoveries support reclassification of LCH as a tissue-infiltrating, clonal neoplasm derived from myeloid dendritic cells showing a Langerhans cell phenotype. Somatic BRAF-V600E and MAP2K1 mutations have been identified in ~85% of cases of LCH, and pathologic MAPK pathway activation is considered to be universal in LCH. This trial is an open-label, multi-center Phase 2 study to evaluate the safety and efficacy of the pan-RAF inhibitor DAY101 in patients with relapsed/refractory LCH with pathologic somatic mutations in genes encoding tyrosine kinase receptors, RAS or RAF. DAY101 will be given orally at the recommended phase 2 dose (RP2D). The primary end point will be the overall response rate. Event-free, progression-free, and overall survival will be assessed as secondary end points. Tumor biopsies and serial blood specimens will be collected for correlative biology.