A first-in-patient phase I study of BGB324, a selective Axl kinase inhibitor in patients with refractory/relapsed AML and high-risk MDS.

Abstract

2561Background: The RTK Axl represents an independent prognostic factor and therapeutic target in AML. BGB324 is an orally available selective potent Axl inhibitor, which has antileukemic activity in preclinical models of AML. Methods: A standard 3 + 3 dose escalation study was performed to identify the maximum tolerated dose of BGB324 in patients with previously treated AML or high risk MDS. BGB324 was administered as an oral loading dose on days one and two followed by a reduced daily maintenance. Three dose levels were explored 400/100mg, 600/200mg and 900/300mg Results: To date, 13 patients with AML and 3 patients with MDS were treated in the first three dose levels. 6 patients remain on treatment and 11 are evaluable. Therapy has been well-tolerated and the MTD has not yet been reached. The majority of adverse events reported have been Grade 1 and 2. The most common related adverse events are diarrhea and fatigue. One patient with pre-existing cardiac conduction abnormalities discontinued study treat...