The purpose of this phase 1b/2 study is to estimate the treatment effect of study drug measuring progression free survival.

To evaluate the incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicity in subjects with metastatic non-squamous non-small cell lung cancer (NSCLC) treated with AMG 386 in combination with pemetrexed and carboplatin

Inclusion Criteria:

• Histologically confirmed, unresectable stage IV non-squamous non small cell lung cancer (NSCLC)
• Radiographically evaluable disease (measurable or non-measurable) per RECIST 1.1 with modifications
• Adequate hematological, renal, and hepatic function, normal coagulation profile, calculated CrCL ≥ 45 mL/min
• Other criteria may apply

Exclusion Criteria:

• Any prior chemotherapy or targeted therapy for non-squamous NSCLC
• Subjects with adenosquamous histology or any histology subtype containing greater than 10% squamous cells
• Subjects with an epidermal growth factor receptor (EGFR) mutation sensitive to treatment with a tyrosine kinase inhibitor (TKI)
• Subjects with known anaplastic lymphoma kinase (EML4-ALK) translocations
• History or presence of central nervous system metastases
• Central (chest) radiation therapy within 28 days prior to enrollment/randomization, radiation therapy to any other site(s) within 14 days prior to enrollment/randomization
• History of pulmonary hemorrhage or gross hemoptysis within 6 months
• History of arterial or venous thromboembolism within 12 months
• History of clinically significant bleeding within 6 months
• Clinically significant cardiovascular disease within 12 months
• Other criteria may apply