7104 Background: The mechanisms of resistance to EGFR tyrosine kinase inhibitors remain poorly understood but may be related, in part, to dysregulation of downstream apoptotic pathways, such as the PI3K/Akt/PTEN axis. In preclinical models, inhibition of the PI3K/Akt pathway restores gefitinib (Iressa™) sensitivity in resistant cell lines. mTOR is a serine/threonine kinase located downstream of Akt that regulates cellular growth and G1/S cell cycle progression. RAD001 is an orally available mTOR inhibitor that inhibits growth of cancer cell lines, including A549. We undertook this phase I/II study to characterize the safety, pharmacokinetics (PK), and antitumor activity of the combination of gefitinib and RAD001 in pts with advanced NSCLC with no prior history of EGFR-directed therapy. Methods: Phase I: 3-pt cohorts with no intrapatient escalation, at RAD001 dose levels of 5 and 10 mg daily. All pts received gefitinib 250 mg daily. PK studies were performed over a 3-week period during which pts received a...