Phase I study of OSI-906, dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) in combination with erlotinib (E) in patients with advanced solid tumors.

3016 Background: OSI-906 is an inhibitor of IGF-1R and IR, which are often upregulated in tumors. Compensatory cross-talk between IGF-1R and EGFR contributes to resistance to agents targeting either pathway, supporting evaluation of dual receptor inhibition. Methods: Patients (pts) with advanced solid tumors received escalating doses of OSI-906 plus continuous E (100/150 mg/d). Objectives included determination of MTD, safety, pharmacokinetics (PK), and tumor response (RECIST). Results: To date, 30 pts were enrolled (17M/13F, median age 59 yrs) and 26 treated. Two OSI-906 dosing schedules were investigated, combined with 100 mg/day E. Intermittent OSI-906 (S1) was administered QD 1-3 q7 d to dose cohorts (mg/pt) of 50 (3 pts), 75 (3); 150 (3), 300 (4); 450 (3) and 600 (3), and continuous OSI-906 (S2) QD to dose cohorts 50 (4) and 100 (3). Median number of weeks on trial was 6 (range 0-23+). DLTs of g4 elevated ALT/AST and g3 fasting hyperglycemia occurred in 2 pts at OSI-906 S1 600 mg + E 100 mg. Transien...