Phase I trial of novel kinesin spindle protein (KSP) inhibitor SB-715992 IV days 1, 8, 15 q 28 days

2004 Background: The mitotic kinesin KSP plays an exclusive and essential role in assembly and function of the mitotic spindle. KSP represents a novel target for development of therapeutics against cancer. SB-715992 is a unique and selective inhibitor of KSP, that is preferentially overexpressed in malignant cells, functions exclusively in mitosis, and is not expressed in terminally differentiated neurons. In pre-clinical studies in a broad range of human tumor xenografts, doses of SB-715992 below the MTD produced tumor regression and cures. Methods: The current study determines the safety, MTD, and PK profile of SB-715992 administered over 1-hour on days 1, 8, 15 q 28 days. Results: 27 patients (pts) (M/F 15/12) with solid tumors were treated at doses of 1 to 8 mg/m2. Median age was 53 years (range 29–78). Common tumor types included CRC (5), RCC (4), breast (4), and lung (3). 2 pts developed DLT at 8 mg/m2 consisting of Grade (Gr) 3 neutropenia, resulting in the inability to administer the d 15 dose. Th...