Final results of a phase I study evaluating the combination of linsitinib, a dual inhibitor of insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor (IR) with weekly paclitaxel (PAC) in patients (Pts) with advanced solid tumors.

e13502 Background: Linsitinib (OSI-906) is an oral inhibitor of IGF-1R and IR. Increased IGF-1R and IR activity is observed in human cancers and implicated in resistance to chemotherapy. In preclinical studies, linsitinib blocked IGF-1R/IR-AKT pathway activity evoked by PAC treatment. This study combines linsitinib + a cytotoxic agent. Methods: Pts with advanced solid tumors received weekly IV PAC (80mg/m2) in 21-day cycles with intermittent linsitinib (Arm A, d1-3q7d) or continuous linsitinib (Arm B, B2 and B3, twice daily (BID) d1-21). The primary objective was to determine the maximum tolerated dose (MTD) of linsitinib + PAC using a standard 3+3 phase I design. Results: 58 pts were treated (49F:9M, median age 58 yrs). Linsitinib doses of 300mg to 600mg daily (QD) d1-3q7d in Arm A and 75mg to 150 mg BID in Arm B were evaluated. Dose limiting toxicities in Arm A (n=27) were grade G3 neutropenia, G2 neuropathy and G3 deep vein thrombosis (DVT), and in Arm B (n=31) were G3 hyperglycemia, G3 fatigue (n=2) a...