Background: ACC & TNBC are tumors associated with Notch signaling pathway dysregulation. Ayala is targeting Notch activated tumors with investigational small molecule pan-Notch g-secretase inhibitors AL101 & AL102. AL101 is currently being investigated in 2 phase II open-label, single-arm, multicenter studies in ACC (ACCU-RACY; NCT03691207) and TNBC (TENACITY; NCT04461600) in patients harboring known Notch1-4 activating alterations. Notch interacts via crosstalk with other signaling pathways, and here we describe testing for their identity to provide guidance for future combination studies with AL101.