Co-Primary Objectives

The co-primary objectives for this study are as follows:

• To evaluate the efficacy of onartuzumab + mFOLFOX6 compared with

placebo + mFOLFOX6 in patients with HER2-negative metastatic gastroesophageal cancer

(GEC) in the first-line setting as measured by progression-free survival (PFS) in all patients

• To evaluate the efficacy of onartuzumab + mFOLFOX6 compared with

placebo + mFOLFOX6 in patients with HER2-negative metastatic GEC in the first-line

setting as measured by PFS in the subgroup of patients with Met-positive tumors

Secondary Objectives

The secondary objectives for this study are as follows:

• To evaluate the safety of onartuzumab + mFOLFOX6 compared with

placebo + mFOLFOX6 in patients with HER2-negative metastatic GEC, focusing on all

adverse events, National Cancer Institute Common Terminology Criteria for Adverse Events

(NCI CTCAE) Grade ≥ 3 adverse events, and Grade ≥ 3 laboratory toxicities

• To evaluate the efficacy of onartuzumab + mFOLFOX6 relative to placebo + mFOLFOX6 as

measured by overall survival (OS) in all patients and in Met-positive populations

• To evaluate the efficacy of onartuzumab + mFOLFOX6 relative to placebo + mFOLFOX6 as

measured by overall response rate (ORR) and duration of response (DOR) in all patients

and in Met-positive populations

• To characterize the pharmacokinetics of onartuzumab when given with mFOLFOX6

• To evaluate the possible effect of onartuzumab on the pharmacokinetics of oxaliplatin and

5-FU by comparison of the respective onartuzumab and placebo combination treatments

• To evaluate serum levels and incidence of anti-therapeutic antibodies (ATAs) against onartuzumab

Exploratory Objectives

The exploratory objectives for this study are as follows:

• To study the correlation between Met expression levels, as measured by

immunohistochemistry (IHC), and clinical outcomes

• To evaluate the potential association of exploratory tissue, serum and plasma biomarkers,

circulating tumor cells in blood, and inflammatory markers with study drug response,

including efficacy and/or adverse events, and to increase knowledge and understanding of

gastric cancer biology

• To explore potential relationships between pharmacokinetics, safety, and activity