First-in-human study of 4SC-205 (AEGIS), a novel oral inhibitor of Eg5 kinesin spindle protein.

2564 Background: 4SC-205 is a potent small molecule inhibitor of the kinesin spindle protein Eg5 with broad anti-tumour activity in vitro and in vivo. Currently, 4SC-205 is the only oral available Eg5 inhibitor at clinical stage. Oral availability allows for flexible dosing in order to determine an optimal therapeutic window. Methods: Patients (pts) with solid tumors were dosed either once weekly (ow) at days 1 and 8 or twice weekly (tw) at days 1, 4, 8, and 11 or continuously (con) within a 21-day cycle. Dose escalation followed a 3+3 design. Primary objectives comprised safety, tolerability, definition of MTD/DLT and pharmacokinetic (PK) characterization. Secondary objectives include assessment of anti-tumour effect, measurement of M30/M65 cytokeratin-18 and pH3 in skin biopsies. Results: 56 Pts were enrolled at dose levels of 25mg (N=3), 50mg (N=3), 100mg (N=6), 150mg (N=6) and 200mg (N=13) ow; at 50mg (N=3), 75mg (N=7), and 100mg (N=5) tw; and at 10mg (N=3), 20mg (N=3) and 30mg (N=4) con. DLT was reac...