A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed mCRC not amenable to potentially curative
resection with at least one measurable metastatic lesion, as defined by RECIST v1.1

- Eastern Cooperative Oncology Group (World Health Organization) performance status of 0
or 1

- Adequate hematologic, liver, coagulation, renal, and cardiovascular function

- Recovery from all reversible AEs of previous medical therapies to baseline or National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1,
except for alopecia (any grade)

- Negative serum pregnancy test within 7 days prior to starting study treatment in
premenopausal women and women less than (< 2) years after the onset of menopause

Exclusion Criteria:

- Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase
inhibitors, immunotherapy, hormonal therapy) before Day 1 of Cycle 1 for treatment of
mCRC

- Malignancies other than CRC within 5 years prior to randomization, except for those
with a minimal risk of metastasis or death, such as adequately treated carcinoma in
situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer,
ductal carcinoma in situ treated surgically with curative intent

- Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to
Day 1 of Cycle 1, except palliative radiotherapy to bone lesions within 7 days prior
to Day 1 of Cycle 1

- Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 28 days prior to Day 1 of Cycle

- Pregnant or lactating women

- Symptomatic central nervous system (CNS) metastases or carcinomatous meningitis.
Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal
metastatic involvement, have completed previous therapy (including radiation and/ or
surgery) at least 4 weeks prior to study drug administration, are not receiving
steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS
involvement

- Active infection requiring IV antibiotics

- Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory
drugs (NSAIDs), inhaled corticosteroids, or the equivalent of less than or equal to
(
- Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2

- Significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1
of Cycle 1

- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation

- Current use of anticoagulants at therapeutic doses within 7 days prior to study drug
administration. Prophylactic use of unfractioned heparin or low molecular weight
heparin is permitted

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 of Cycle 1 or abdominal surgery, abdominal interventions or significant
abdominal traumatic injury within 60 days prior to Day 1 of Cycle 1

- History of intra-abdominal inflammatory process within 6 months prior to Day 1 of
Cycle 1 including but not limited to peptic ulcer disease, diverticulitis, or colitis

- Colonic prosthesis (stent) implant in place

- History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI)
perforation or intra abdominal abscess within 6 months prior to Day 1 of Cycle 1

- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction
including sub-occlusive disease related to the underlying disease or a requirement for
routine parenteral hydration, parenteral nutrition, or tube feeding within 6 months
prior to Day 1 of Cycle 1

- Chronic daily treatment with NSAID (occasional use for the symptomatic relief of
medical conditions, for example headache or fever is allowed)

- Chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisolone
equivalent) excluding inhaled steroids

- Evidence of abdominal free air not explained by paracentesis or recent surgical
procedure

- Metastatic disease that involve major airways or blood vessels, or centrally located
mediastinal tumor masses (< 30 millimeter from the carina) of large volume

- History of bronchopulmonary hemorrhage NCI CTCAE >/= Grade 2 within 2 months prior to
randomization

- Severe, nonhealing or open wound, active ulcer, or untreated bone fracture

- Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene
polymorphism predisposing the patient for 5-FU toxicity

- Any other condition, diseases, metabolic dysfunction, active or uncontrolled
infections/inflammation, physical examination finding, mental status or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates participation in the clinical study due to safety concerns, compliance
with clinical study procedures or that may affect the interpretation of the results