A first-in-human phase I dose-escalation study of MK-1496, first-in-class orally available novel PLK1 inhibitor, in patients with advanced solid tumors.

3012 Background: Polo-like kinase 1 (PLK1) is a serine/threonine kinase involved in cell cycle control, especially has key roles in multiple steps of mitosis progression. Overexpression of PLK1 is frequently observed in a range of human tumors, suggesting PLK1 function is important for proliferation of cancer cells. MK-1496 is an orally available highly potent and selective inhibitor of PLK1 with demonstrated anti-proliferative activity in vitro and in vivo. Methods: Sequential cohorts of 3 to 6 patients (pts) with progressive advanced or metastatic solid tumors received an MK-1496 dosing regimen of days 1 and 3 of each treatment wk for 3 wks followed by 1 wk rest period, following a toxicity guided dose escalation design. A total of 17 pts were treated at doses from 20 to 120 mg. Results: Reversible hematotoxicity was the main side effect constituting DLTs observed at 100 mg and 120 mg. The most frequent G3/4 adverse events were leukopenia (35%), neutropenia (35%), thrombocytopenia (29%), febrile neutrop...