This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RO5490258 (MetMab) in combination with either of two backbone chemotherapy regimens in the first-line setting in patients with incurable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, patients will be randomized to receive 4 cycles of bevacizumab (Avastin) 15 mg/kg iv, paclitaxel 200 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMab 15 mg/kg iv or placebo on Day 1 of each 21-day cycle. In Cohort 2, patients will be randomized to receive pemetrexed 500 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or placebo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically or cytologically confirmed Stage IIIB or Stage IV non-squamous non-small cell lung cancer (NSCLC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• For patients who received prior adjuvant chemotherapy or chemoradiotherapy: a treatment-free interval of at least 12 months since last chemotherapy or chemoradiotherapy cycle
• Adequate tissue for central immunohistochemical (IHC) assay of Met receptor, and epidermal growth factor receptor (EGFR) testing if EGFR status is unknown
• Radiographic evidence of disease

Exclusion Criteria:

• Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC
• Evidence of mixed NSCLC with a predominance of the squamous cell type
• Prior exposure to experimental treatment targeting either the hepatocyte growth factor (HGF) or Met pathway
• Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator, unless that treatment is unavailable or refused by the patient
• Known central nervous system (CNS) disease, other than stable, treated brain metastases
• History of another malignancy in the previous 3 years, except for history of in situ cancer that was treated surgically with curative intent, localized prostate cancer that has been treated surgically with curative intent, or basal or squamous cell skin cancer
• Uncontrolled diabetes
• Pregnant or lactating women
• Impaired bone marrow, liver or renal function (as defined by protocol)
• Significant history of cardiovascular disease
• Positive for HIV infection