8051 Background: R is an oral inhibitor of the mammalian target of rapamycin (mTOR) in clinical development as an anticancer agent. Clinical benefit including objective tumor responses were observed in pts with NSCLC receiving R. E is an oral epidermal growth factor receptor inhibitor (EGFRI) approved for the treatment of NSCLC pts failing C. Preclinical evidence suggests that R may enhance EGFRI anti-tumor activity and reduce resistance to EGFRI. Methods: Patients with advanced NSCLC, failing ≤ 2 prior C regimens, ECOG PS ≤2, adequate bone marrow and liver function were eligible. Phase 1 part assessed the combination of R and E using a standard “6+6” dose-escalation design based on the rate of dose-limiting toxicity (DLT) and pharmacokinetic (PK) drug- drug interaction (DDI) during the first 28 days of combined treatment. A range of R doses administered in either a daily (qd) or a weekly (qw) schedule were evaluated in combination with different daily doses of E. Results: 61 pts treated in 7 cohorts: Male/Female 32/29, ever smoker/never smoker 49/12, prior therapies 1/2 31/30. Doses and schedules evaluated: R 2.5mg qd, 5mg qd, 30mg qw, 50mg qw in combination with qd doses of E 75mg, 100mg, and 150mg. R 2.5mg qd + E 150mg qd, R 5mg qd + E 75mg qd, and R 50mg qw + E 150 mg qd, were established as feasible dose regimens. DLTs observed were: mucositis (5), rash (4), diarrhea (4), vomiting (1) and neutropenia (1). Available duration of exposure of the combination was 0.2–25.8 months in daily cohorts and 0.1–2.9 months in weekly cohorts. Preliminary best overall response based on RECIST as per Investigator lesion assessment was: CR (1), PR (3), SD (17), PD (18). Conclusions: Phase 1 part of the study established feasible doses of R in combination with E with promising early indication of clinical efficacy. Phase 2 of the study will evaluate the efficacy of dose regimens established in the phase 1 part. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Genzyme Novartis Novartis