AMG706 active vs. solid tumors

Dr. Lee Rosen of the John Wayne Cancer Institute in Santa Monica, Calif., presented abstract no. 3013, “Safety and pharmacokinetics of AMG706 in patients with advanced solid tumors.”

This phase I trial was open to patients with many different types of solid tumors. AMG706 was generally well tolerated up to 125 mg. per day, every day. A total of 71 patients were entered into the trial. Forty-nine received the dose eventually chosen for further study — 125 mg./day.

In all, 56 patients are evaluable. Three patients have been on the study for more than one year. Four percent of patients had partial responses, and 61 percent had stable disease. The duration of stable disease was not identified in the study.

Dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) was used to evaluate the permeability of the blood vessels supplying blood to the tumors (tumor vascular permeability).

DCE-MRI showed reductions up to 37 percent in initial “area under the curve” on the third day and up to 61 percent on day 21 of treatment.

Fatigue and high blood pressure were the most common side effects. The high blood pressure was generally fairly easy to manage, with 23 percent of patients requiring some type of blood pressure medication.

The pharmacokinetic profile appeared desirable. Once per day dosing of AMG706 achieved the desired blood concentrations.

There was no evidence of drug accumulation (levels at day 28 were similar to those of the first day). AMG706 was found to be a weak inhibitor of CYP3A enzymes and clinically significant drug interactions are not predicted.