Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Exclusion Criteria

• •1. Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR) inhibitors
• •2. Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib
• •4. Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine, and/or pemetrexed including contraindications, hypersensitivity, or prior administration
• •5. Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for radiotherapy) prior to randomization
• •6. Pregnant or breastfeeding
• •7. Significant gastrointestinal disorder that could, in the opinion of the Investigator, interfere with the absorption of ARQ 197 and/or erlotinib
• •8. Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
• •9. Other malignancies within the last three years, with the exception of adequately treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a prostate-specific antigen (PSA) value \< 0.2 ng/mL or basal or squamous cell carcinoma of the skin
• •10. Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• •11. Major surgical procedure within 4 weeks prior to randomization
• •12. History of cardiac disease: Congestive heart failure defined as Class II to IV per New York Heart Association classification; Active coronary artery disease; Previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; Myocardial infarction that occurred within 6 months prior to study entry (myocardial infarction that occurred \> 6 months prior to study entry is permitted)
• •13. Clinically unstable central nervous system metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by MRI or CT scan within 4 weeks of randomization and have central nervous system \[CNS\] metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)
• •14. Known EGFR-mutation positive status