A Phase I Study of MK-5108, an Oral Aurora A Kinase Inhibitor, in Both Monotherapy and in Combination with Docetaxel in Patients with Advanced Solid Tumors.

The phase I study of MK-5108, an oral Aurora A kinase inhibitor, involved 34 patients with advanced solid tumors to assess its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. The study was divided into monotherapy (MT) and combination therapy (CT) with docetaxel. In MT, no dose-limiting toxicities (DLTs) were identified, and the maximum tolerated dose (MTD) was not established, with doses up to 1,800 mg being well tolerated. In CT, a DLT of febrile neutropenia was observed, along with other grade 3/4 adverse events. The pharmacokinetic profile showed dose-proportional increases in plasma concentration after the first dose. Stable disease was observed in 7 MT patients and 4 CT patients, with 2 partial responses in CT. The study concluded that MK-5108 was well tolerated and showed potential clinical activity as a single agent.