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

• ECOG performance status of 0 or 1

• Life expectancy > 3 months

• Histologically confirmed adenocarcinoma of the stomach or GEJ with inoperable, metastatic

disease, not amenable to curative therapy

• Adequate archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tissue for central IHC assay of Met receptor and HER2 status (if unknown)

Local assessment of HER2 status is acceptable.

• Radiographic evidence of disease; measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

Patients with peritoneal disease would generally be regarded as having evaluable disease and allowed to enter the trial.

• For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use an adequate method of

contraception (a method with a failure rate of < 1% per year, such as hormonal implants, combined oral contraceptives, or a vasectomized partner) during the treatment period and

for at least 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin

• For men: agreement to use a barrier method of contraception during the treatment period and for at least 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin