Phase I trial of ARRY-520 in relapsed/refractory multiple myeloma (RR MM).

8132 Background: Kinesin Spindle Protein (KSP) is required for cell cycle progression through mitosis. ARRY-520 is a potent, selective inhibitor of KSP, arresting cells in mitosis with subsequent onset of apoptosis. Malignancies, such as MM, depending on the survival protein MCL-1 rapidly undergo apoptosis following treatment with ARRY-520. ARRY-520 shows potent activity in preclinical MM models, providing a strong rationale for its clinical investigation in this disease Methods: This phase I study was designed to evaluate the safety, pharmacokinetics and pharmacodynamics of ARRY-520 administered intravenous (IV) on D1 and D2 q 14 days without/with granulocyte colony stimulating factor (G-CSF). Patients (pts) with RR MM or plasma cell leukemia with ≥ 2 prior lines of therapy (including a bortezomib and IMiD-based regimen, unless refusing or ineligible for this therapy) were eligible. Cohorts of at least 3 pts are being enrolled in a classical 3+3 dose escalation design. Pts are treated for 2 cycles for sa...