A Study of XL184 (Cabozantinib) With or Without Erlotinib in Subjects With Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria-Phase 1:

• Subjects had pathologically confirmed NSCLC and currently have Stage IIIb or IV NSCLC
• Subjects had failed treatment with erlotinib at 150 mg qd
• Subjects had tolerated erlotinib at the dose of the cohort in which they were enrolled (or at a higher dose) for at least 6 weeks (or for the duration of treatment if disease progression had occurred during treatment with erlotinib for less than 6 weeks)
• The subject was at least 18 years old
• The subject had an ECOG performance status of 1.5 mg/dL calculated creatinine clearance ≥ 60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal, amylase and lipase 0.5 teaspoon of red blood or other signs indicative of pulmonary hemorrhage
• The subject had the presence of cavitation, endobronchial lesion or a lesion abutting a major blood vessel
• The subject had serious intercurrent illness, such as uncontrolled hypertension (sustained blood pressure [BP] readings of > 140 mmHg systolic or > 90 mmHg diastolic not controlled with anti-hypertensive medication), unhealed wounds from recent surgery or clinically significant cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris within 3 months or myocardial infarction within 6 months before the first dose of study drug
• The subject was pregnant or breastfeeding
• The subject had an active infection requiring systemic treatment
• The subject had an allergy or hypersensitivity to components of either the cabozantinib or erlotinib formulations
• The subject was incapable of understanding and complying with the protocol or unable to provide informed consent

Inclusion Criteria-Phase 2

• Subjects had pathologically confirmed NSCLC and currently have Stage IIIb or IV NSCLC
• Subjects had: Documented radiological PD, following a prior response, per investigator assessment, to monotherapy with erlotinib, OR; Documented radiological PD, per investigator assessment, following stable disease of at least 6 months on monotherapy with erlotinib
• Subjects who had received subsequent anti-cancer therapy after having progressed on erlotinib (as defined above) also had to have documented radiological PD per investigator assessment to their most recent anti-cancer therapy. If the most recent anti-cancer therapy was erlotinib after having previously progressed on erlotinib (as defined above) the subject also had to have documented radiological PD per investigator assessment to their most recent course of erlotinib
• Subjects had to have tolerated erlotinib at the maximal dose that would be administered in Phase 2 (or at a higher dose) for a minimum of 6 weeks
• Subjects had measurable disease per RECIST
• Subjects had to have 15 unstained consecutive slides of archival or fresh tumor tissue (from one tumor block, frozen tumor tissue, or a paraffin block) identified and designated for shipment to the sponsor if permitted by local regulations (including IRB [Institutional Review Board] policies). The eligibility of subjects with 1.5 mg/dL calculated creatinine clearance ≥ 60 mL/min, ALT and AST ≤ 2.5 times the upper limit of normal, amylase and lipase 0.5 teaspoon of red blood within 3 months before the first dose of study treatment, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• The subject had cavitating pulmonary lesion(s), known endobronchial disease or a pulmonary lesion abutting or encasing a major blood vessel
• The subject had serious intercurrent illness, such as uncontrolled hypertension (sustained BP readings of > 140 mmHg systolic or > 90 mmHg diastolic not controlled with anti hypertensive medication), unhealed wounds from recent surgery or clinically significant cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris withi