Anthony Mato, MD, MSCE, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the multicenter phase I trial (NCT03740529) of LOXO-305, a next-generation, highly selective, oral, non-covalent bruton tyrosine kinase inhibitor (BTKi), in patients with B-cell malignancies who had acquired resistance and/ or unacceptable toxicities following an irreversible BTKi. Results from the first-in-human trial show high and durable response rates with LOXO-305 in heavily pretreated chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients. This interview took place at the American Society of Hematology (ASH) 2019 Annual Meeting and Exposition in Orlando, FL.