Trovagene announced positive data from a preclinical in-vivo study examining the combination of their PLK1 inhibitor, PCM-075, with a leading investigational FLT3 Inhibitor. This FLT3 mutant xenograft model shows PCM-075 in combination with Quizartinib resulted in 96% tumor growth inhibition versus monotherapy with Quizartinib (81%) or PCM-075 (76%). This research data is planned for future publication.
"Thirty percent of patients with AML harbor a FLT3 mutation. This represents an opportunity for combination therapy with PCM-075," said Bill Welch, CEO of Trovagene. "We are encouraged by this initial preclinical data as we continue to identify potential combination therapies using PCM-075 within diverse AML patient populations."
PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic malignancies, as well as solid tumors such as adrenocortical, breast, prostate, ovarian, lung, gastric and colon cancers. PCM-075 is orally bioavailable and has been explored in an initial Phase 1, open-label, dose-escalation safety study in patients with advanced metastatic solid tumor cancers. Trovagene plans to initiate clinical trials of PCM-075 in AML, since it has significant advantages over prior PLK1 inhibitors evaluated in this indication, including a higher selectivity, greater potency, oral bioavailability and shorter half-life.
Acute myeloid leukemia (AML) is a hematologic malignancy in which myeloid lineage cells of the bone marrow cease to differentiate appropriately, resulting in a marked increase in the number of circulating immature blast cells. As a consequence, the counts of mature red blood cells, platelets, and normal white blood cells decline, causing fatigue, shortness of breath, bleeding, and increased susceptibility to infection. Patients harboring mutations in the FLT3 receptor tyrosine kinase have a particularly poor prognosis; however, significant progress has been made by the emergence of a variety of targeted inhibitors capable of suppressing FLT3 signaling.