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. Transient g1-2 hyperglycemia (12 pts, 46%) and elevation of insulin levels (9 pts, 35%) were consistent with IR inhibition. E-related skin rash occurred in 22 (85%) pts (g1/2/3: 27/54/4%). Other adverse events related to OSI-906 and E in ≥2 pts were of g1-2 severity: fatigue (31%), diarrhea (31%), anorexia (12%), nausea (15%), dyspepsia, dysgeusia and vomiting (8% each). Preliminary PK data indicate that exposure of OSI-906 was not altered significantly after co-administration with E. Exposure of E and its main metabolite OSI-420 appears similar to previous studies, suggesting lack of PK interaction between OSI-906 and E. Stable disease of 12-23+ weeks was seen in 4/7 pts on S2 including cases of adrenocortical carcinoma, Ewings sarcoma, chordoma and adenocarcinoma of unknown primary. Conclusions: Intermittent OSI-906 with 100mg E had minor toxicity up to 450 mg, with DLTs at 600 mg. Preliminary data indicate that continuous OSI-906 with E is also well-tolerated, and is capable of inducing disease stabilization. Dose escalation continues including a continuous BID dosing schedule, aiming to define MTDs using E at 150 mg QD. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI Pharmaceuticals OSI Pharmaceuticals OSI Pharmaceuticals OSI Pharmaceuticals OSI Pharmaceuticals