The purpose of this study is to determine the best confirmed response rate of daily administration of the multiple receptor tyrosine kinase (RTK) inhibitor (including EGFR and VEGFR2) XL647 in subjects with NSCLC who have progressed after responding to treatment with either erlotinib or gefitinib.

Inclusion Criteria:

• Histologically confirmed diagnosis of unresectable Stage IIIB or Stage IV relapsed or recurrent NSCLC.

• Subjects must have:

  1. documented (radiological or clinical) progressive disease (PD) following a prior response (including stable disease) to monotherapy with erlotinib or gefitinib that was administered for at least 12 weeks prior to progression OR
  2. a documented T790M EGFR mutation

• Measurable disease defined according to RECIST

• ECOG performance status of 0 or 1.

• Sexually active subjects must use an accepted method of contraception during the course of the study.

• Female subjects of childbearing potential must have a negative pregnancy test at enrollment.

Exclusion Criteria:

• Received radiation to ≥25% of his or her bone marrow within 30 days of XL647 treatment.
• Received erlotinib or gefitinib, or other anticancer therapy within 14 days of the first dose of study drug.
• Received an investigational drug (excluding erlotinib or gefitinib) within 30 days of the first dose of study drug.
• Receiving anticoagulation therapy with warfarin.
• Not recovered to Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study enrollment.
• Corrected QT interval (QTc) of >0.45 seconds.
• Progressive, symptomatic, or hemorrhagic brain or leptomeningeal metastases.
• Requires steroid or anticonvulsant therapy for the treatment of brain metastases.