Cytokinetics presents positive interim data from Phase I/II breast cancer study

The primary objectives of the Phase I portion of this clinical trial are to determine the dose limiting toxicities (DLTs) and maximum tolerated dose and to assess the safety and tolerability of ispinesib administered as a one-hour intravenous infusion on days one and 15 of a 28-day cycle.

The secondary objectives are to characterize the pharmacokinetics of ispinesib on this schedule and to evaluate the effect of ispinesib on biomarkers of cell proliferation in patients with accessible tumors.

Interim results were provided for 15 patients who had been enrolled at one of three dose levels of ispinesib (10mg/m2, 12mg/m2 and 14mg/m2) and had completed at least one cycle of treatment. At the time of data analysis, 13 patients were evaluable for safety and efficacy. Tumor response was assessed for an additional two patients subsequently treated at 12mg/m2. Two of seven patients treated at the 14mg/m2 dose level had protocol-defined DLTs of transient Grade 3 increases in the liver enzymes ALT and AST following cycle 1, day 15 dosing. As a result of these DLTs at 14mg/m2, the 12mg/m2 cohort was expanded to six patients, and no DLTs were observed at the latter dose level.

Because the 12mg/m2 dose level was thus demonstrated to be tolerable, and because the authors concluded that the DLTs of Grade 3 ALT/AST increases at 14mg/m2 dose level had a questionable temporal relationship to the administration of ispinesib, plans are underway to further evaluate the 14mg/m2 dose level.

The best responses observed to date in the Phase I portion of this ongoing Phase I/II clinical trial were investigator-reported reductions of 30% or greater in the sum of the target lesion diameters, reported in three patients. One of these patients had an investigator-reported partial response according to the response evaluation criteria in solid tumors (RECIST). Three patients had investigator-reported stable disease of four months or longer according to RECIST.

Henry Gomez, chief of medical oncology, Departamento de Investigacion, Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, said: “Ispinesib has been well-characterized in prior studies and has shown a favorable tolerability profile. These data support the safety and tolerability of this drug candidate on a more dose-dense schedule and suggest the potential for amplified clinical activity.”