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)

This is a randomized, placebo-controlled, double blind phase 2 study designed to compare treatment with ARQ 197 plus erlotinib to erlotinib plus placebo in patients with non-small cell lung cancer. The study will enroll patients who have had one prior chemotherapy regimen (other than erlotinib) for NSCLC. The study will evaluate progression-free survival between the two arms.

A total of 154 patients will be enrolled.

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