A Randomized Phase 2 Study of Erlotinib + ARQ 197 Versus Erlotinib + Placebo in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

Provide signed and dated informed consent prior to study-specific screening procedures
≥ 18 years old
Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC
≥ one prior chemotherapy regimen (including adjuvant chemotherapy)(not to have included erlotinib or other EGFR inhibiting agent)
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Male or female patients of child-producing potential must agree to use double barrier contraception, oral contraceptives or avoidance of pregnancy measures during the study and for 90 days after the last day of treatment
Females of childbearing potential must have a negative serum pregnancy test
Good organ function
Confirmed availability of archival pathology samples (10 unstained paraffin-embedded slides) or tissue block suitable for subsequent analysis of KRAS, EGFR, and c-Met

Exclusion Criteria:

Previous receipt of erlotinib or other EGFR inhibiting therapy
Receipt of any anti-tumor treatment for NSCLC within 4 weeks (2 weeks for radiotherapy) prior to the start of designated treatment
Documented major surgical procedure within 4 weeks prior to randomization.
Symptomatic central nervous system metastases either considered in the opinion of investigator to be clinically unstable or which require steroids, anti-epileptics, or other symptom-relieving medications
Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures
Significant gastrointestinal disorder that, in opinion of Investigator, could interfere with the absorption of ARQ 197 and/or erlotinib (e.g. Crohn's disease, small or large bowel resection, malabsorbtion syndrome)
Unable or unwilling to swallow the complete dose of erlotinib or ARQ 197
Any known contraindication to treatment with ARQ 197 or erlotinib
Any known hypersensitivity to any of component of ARQ 197 or erlotinib
Other malignancy within 5 years of randomization, with the exception of adequately treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a PSA value < 0.2 ng/ml or basal or squamous cell carcinoma of the skin
Previously diagnosed grade 3 or 4 (CTCAE) bradycardia or other heart arrhythmia
Any other significant co-mormid condition that, in opinion of the Investigator, would impair study participation or cooperation
Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection