Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with @entity1311 and XXXX .

@entity1 @entity43 @entity16394 @entity882 @entity5 @entity3003 @entity294 @entity1149 @entity1311 @entity1295 @entity442 @entity2301 @entity2856 @entity4854
INTRODUCTION: This phase 1 study was conducted to determine the recommended phase 2 dose of the selective insulin-like growth factor type 1 receptor ( @entity2856 ) inhibitor figitumumab (F, CP-751,871) given in combination with @entity1311 and @entity3003 in @entity1 with advanced solid @entity5 . METHODS: @entity1 received @entity1311 200 mg/m2, @entity3003 (area under the curve of 6), and F (0.05-20 mg/kg) q3 weeks for up to six cycles. @entity1 with objective response or stable disease were eligible to receive additional cycles of single agent F until disease progression. Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints were investigated. RESULTS: Forty-two @entity1 , including 35 with stages IIIB and IV @entity1149 ( @entity1149 ), were enrolled in eight dose escalation cohorts. A maximum tolerated dose was not identified. Severe adverse events possibly related to F included @entity1295 , @entity294 , @entity4854 , gamma @entity16394 transpeptidase elevation, and @entity882 (one case each). F plasma exposure parameters increased with dose. Fifteen objective responses (RECIST) were reported, including two complete responses in @entity43 . Notably, levels of bioactive @entity442 seemed to influence response to treatment with objective responses in @entity1 with a high baseline-free @entity442 to @entity2301 ratio seen only in the 10 and 20 mg/kg dosing cohorts. CONCLUSIONS: F was well tolerated in combination with @entity1311 and @entity3003 . Based on its favorable safety, pharmacokinetic, and pharmacodynamic properties, the maximal feasible dose of 20 mg/kg has been selected for further investigation.
