Abstract B61: Multicenter phase I clinical trial of an insulin like growth factor (IGF-R) inhibitor (IMC-A12) in combination with a mammalian target of rapamycin (mTOR) inhibitor (CCI-779) to overcome resistance to mTOR inhibition

Mammalian target of rapamycin (mTOR) inhibitors mediate AKT activation through a type I insulin‐like growth factor receptor (IGF‐1R)‐dependent mechanism, resulting in resistance to mTOR inhibition. Combining an mTOR inhibitor with an IGF‐1R antibody/inhibitor is expected to enhance mTORtargeted anticancer therapy. This NCI‐CTEP sponsored multicenter phase I clinical trial funded by R‐21 mechanism was aimed to define the maximum tolerated dose (MTD), biologic effects, and metabolic activity, individually and in combination, of IMC‐A12, a fully humanized IgG1 monoclonal antibody directed at the IGF‐IR, and temsirolimus, an inhibitor of mTOR.Methods: A standard “3+3” design used a fixed dose of 25 mg IV weekly of temsirolimus with an escalating weekly dose of IV IMC‐A12 at 3, 4 and 6 mg/kg with no intrapatient dose escalation; 32 patients with advanced cancer (13 male, 19 female) were enrolled …