Inclusion Criteria:

• Histologically confirmed NSCLC and Stage 3b or 4 NSCLC (Phase 1 only), Stage 3b or 4 NSCLC (Phase 2 only)
• Documented progressive disease following a prior RECIST response to monotherapy with erlotinib OR documented progressive disease following stable disease of at least 6 months on monotherapy with erlotinib (Phase 2 only)
• Must have tolerated erlotinib at the maximal dose that will be administered in Phase 2 only (or at a higher dose) for a minimum of 6 weeks
• Measurable disease per RECIST (Phase 2 only)
• At least 18 years old
• ECOG performance status of 0 or 1
• Adequate organ and marrow function
• Sexually active subjects must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study treatment (excluding women who are not of child bearing potential and men who have been sterilized).
• Female subjects of childbearing potential must have a negative pregnancy test at enrollment
• No other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix or malignancy diagnosed ≥ 2 years previously, and currently with no evidence of disease).
• Capable of understanding and complying with the protocol, and written informed consent

Exclusion Criteria:

• Received anti-cancer treatment within 4 weeks, except erlotinib, prior to first dose (Phase 1 only)

• In Phase 2 only: the subject has received:

  • Small molecule inhibitors of VEGFR2/KDR OR
  • An investigational anti-cancer agent within 4 weeks of the first dose of study drug OR
  • An investigational agent that targets EGF or EGFR at any time OR
  • An approved agent that targets EGF or EGFR (with the exception of erlotinib and gefitinib) at any time unless approved by Exelixis OR
  • Anti-cancer therapy within 4 weeks (with the exception of gefitinib and erlotinib) of the first dose of study drug OR
  • Prior therapy with a c-Met inhibitor
• Not recovered to NCI CTCAE v.3 Grade ≤1 from clinically significant adverse events due to antineoplastic agents, investigational drugs, or other medications administered prior to study enrollment
• Symptomatic or uncontrolled brain metastases requiring current treatment, including steroids and anticonvulsants
• History of significant hematemesis or recent history of hemoptysis
• Presence of cavitation, central lesion, or lesion abutting a major blood vessel
• Intercurrent illness such as hypertension or cardiac arrhythmias or recent history of significant disease such as congestive heart failure
• Pregnant or breastfeeding
• Active bacterial or viral infection requiring systemic treatment
• Allergy or hypersensitivity to components of either the XL184 or erlotinib formulations
• Incapable of understanding and complying with the protocol or unable to provide informed consent
• History of idiopathic pulmonary fibrosis or interstitial lung disease