Publication Date:
2008-11-16
Description:
ABT-869 is an orally bioavailable, potent and specific inhibitor of multiple receptor tyrosine kinases (RTKs) including vascular endothelial and platelet growth factor, FLT3, STAT5, and ERK receptors. Since multiple RTKs, particularly FLT3, are commonly expressed and activated in AML/MDS, ABT-869 may prove to be an attractive therapeutic option. The current multi-center, two arm, dose-escalation study was designed to assess the safety, pharmacodynamics, pharmacokinetics (PK) and preliminary anti-tumor activity of ABT-869 as monotherapy in arm A, and to determine the PK, safety profile and potential of a PK or PD mediated drug interaction in patients with AML or MDS treated with ABT-869 plus Cytosine arabinoside (Ara-C) in arm B. No dose was administered on D7 (arm A) and D12 (arm B). In single-agent Arm A enrollment is complete (N=29) with 9, 4, 12 and 4 patients enrolled in each of the 10, 12.5, 15, and 20 mg cohorts, respectively. Dosing began with the 10 mg/day cohort and escalated to the 20 mg/day cohort to define a recommended phase 2 dose (RP2D) of 15 mg. During dose escalation, in the 10 mg cohort, 2 patients experienced DLTs of fatigue while in the 20 mg cohort, 3 patients experienced DLTs of fatigue and 1 patient experienced a DLT of proteinuria. In currently enrolling arm B (N=17), ABT-869 was administered in combination with Ara-C. ABT-869 was initiated on day 6 following administration of Ara-C at 1.5 mg/m2 on days 1–3 (patients ≥64 years old) or days 1–4 (patients
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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