Introduction
human cancer, cancer, T-ALL/LBL, hematologic cancer, T-cell acute lymphoblastic leukemia/lymphoma
PROLIFERATION, CANCER, METASTASIS, HEMATOLOGIC CANCER
Notch signaling plays a critical role in many cellular processes during development to promote cell-cell communication, whereas dysregulation leads to sustained cell proliferation and potential for invasion or metastasis—the hallmarks of cancer. Signaling of the pathway occurs when ligands bind one of four Notch receptors (The oncogenic role of Notch signaling was first observed in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) (Given the importance of Notch signaling in human cancer, several therapeutic approaches have been investigated to inhibit pathway activation, including mAbs against Notch receptors and small-molecule γ-secretase inhibitors (GSI; ref. Here we present the results of the first-in-human, dose-escalation and -confirmation trial of CB-103 across multiple solid and hematologic cancer types to primarily assess safety and tolerability, pharmacokinetics, and evaluate preliminary antitumor efficacy.