Dr. Shadman on the Potential Utility of LOXO-305 in CLL

Mazyar Shadman, MD, a physician and associate professor in the Divisions of Medical Oncology and Clinical Research at Seattle Cancer Care Alliance, discusses the potential utility of LOXO-305 in chronic lymphocytic leukemia (CLL).

LOXO-305 is a third-generation, highly selective BTK inhibitor that inhibits wild-type and C481-mutant BTK, says Shadman. The agent is non-covalent and, therefore, can reversibly bind BTK. As such, LOXO-305 may be effective in treating patients with CLL who progress on ibrutinib (Imbruvica) or acalabrutinib (Calquence), Shadman explains. Additionally, because LOXO-305 is highly selective for BTK, the agent could provide an option to patients who are intolerant to other BTK inhibitors, Shadman says.

During the 2020 ASH Annual Meeting and Exposition, findings from the phase 1/2 BRUIN study showed promising efficacy with LOXO-305 in heavily pretreated patients with CLL or small lymphocytic lymphoma who had poor prognoses. Moreover, the efficacy was not limited to patients with C481 mutations. Although LOXO-305 is in the early stages of clinical development, combination approaches or moving the agent into earlier lines of treatment may be on the horizon, concludes Shadman.