Ambit Begins Dosing Patients in Trial of Lead Kinase Inhibitor

Ambit Biosciences announced that the first patients have been dosed in its Phase I clinical trial to evaluate AC220 in the treatment of acute myeloid leukemia (AML).

The Phase I trial is a multicenter, open-label, sequential-dose-escalation study that will enroll 20 to 40 patients with relapsed or refractory AML. AC220 will be administered daily via oral solution, beginning at 12 mg for 14 days and then increasing until the maximum-tolerated dose is established. In addition to evaluating the safety, tolerability and pharmacokinetics of AC220, the study will measure pharmacodynamics of the drug by monitoring FLT3 receptor phosphorylation and peripheral blood blast counts.

AC220 potently inhibits FLT3, a kinase that is mutated in approximately one-third of AML cases. Patients with FLT3 mutations are less responsive to traditional therapies, according to Ambit.

The FLT3 kinase is inhibited by several kinase inhibitors currently in development as well as by approved drugs such as Sutent, the company added. All of these first-generation, multi-kinase inhibitors are limited in their use by undesirable side effects resulting from off-target activity. Ambit said it has engineered AC220 using KinomeScan to potently target FLT3, KIT, CSF1R/FMS, RET and PDGFRa/b kinases, all of which are validated drug targets.