Inclusion Criteria

Inclusion criteria

1. Subjects must have histologically confirmed unresectable, locally advanced,
recurrent, or metastatic non-squamous NSCLC. Subjects may not have received prior
therapy for their unresectable, locally advanced, recurrent, or metastatic
non-squamous NSCLC. Subjects may have received prior surgery, prior radiotherapy,
and/or prior neoadjuvant or adjuvant chemotherapy (they must have discontinued prior
neoadjuvant or adjuvant chemotherapy at least 12 weeks prior to study entry).

2. Age >21 years

3. ECOG performance status <2 (see Appendix B)

4. Life expectancy of more than 3 months

5. Subjects must have normal organ and marrow function as defined below:

- Leukocytes >3.5 x 109/L

- Absolute neutrophil count >1.25 x 109/L Hemoglobin >100 g/L

- Platelets >125 X 109/L

- Total bilirubin <2 X institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <5
X institutional ULN

- Alkaline phosphatase <5 X institutional ULN

- International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) within institutional ULN

- Calculated creatinine clearance >60 mL/min using the Cockcroft and Gault formula
as follows:

Creatinine clearance (mL/min) = (140 - age) x ideal body weight [kg] 0.814 x serum
creatinine [μmol/L] For women multiply the value from the equation above by 0.85.
Where age is in years, weight is in kg, and serum creatinine is in μmol/L.

6. Women of childbearing potential must have had a prior hysterectomy or have a negative
serum pregnancy test and be using adequate contraception prior to study entry and
must agree to use adequate contraception from study entry through at least 6 months
after discontinuation of study drugs. Men must also agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and from study entry through at least 6 months after discontinuation of
study drugs. Should a woman enrolled in the study or a female partner of a man
enrolled in the study become pregnant or suspect she is pregnant while participating
in this study or within 6 months after discontinuation of the study drugs, the
Investigator should be informed immediately.

7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Subjects who meet any of the following criteria will not be eligible for participation in
the study:

1. Subjects receiving any other investigational agents or anti-cancer therapy.

2. Subjects with brain metastases (subjects must have a CT scan or MRI of the head
within 28 days prior to enrollment to rule out brain metastases), uncontrolled
seizure disorder, or active neurologic disease

3. History of a significant allergic reaction attributed to humanized or human
monoclonal antibody therapy

4. Significant intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia,
or psychiatric illness/social situations that would limit compliance with study
requirements

5. Pregnant women or nursing women

6. Subjects with known HIV infection

7. Known bleeding disorder or coagulopathy

8. Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects
may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.

9. Subjects with known clinically significant gastrointestinal disease including, but
not limited to, inflammatory bowel disease

10. New York Heart Association Classification II, III, or IV (See Appendix D)

11. Subjects with a blood pressure of >140/90 mmHg. The BP should be taken using the
method described in Section 9.3. Subjects taking antihypertensive medications must be
taking ≤ 2 medications to obtain this level of BP control.

12. Subjects with metastases that are currently involving the lumen of the
gastrointestinal tract

13. Subjects with squamous cell carcinoma of the lung

14. Subjects with recent (within the last 8 weeks) hemoptysis >2.5 mL and subjects with
serious bleeding from another site within this timeframe

15. Subjects with current evidence of cardiac ischemia or heart failure within the last 6
months, subjects who are receiving any medications for cardiac ischemia, subjects
with a B-type natriuretic peptide (BNP) value of >100 pg/mL, subjects with a LVEF
<50%, subjects with pulmonary hypertension defined as a peak tricuspid velocity >3.4
m/s on doppler echocardiogram or subjects that have received a total cumulative dose
of ≥400 mg/m2 doxorubicin.

16. Subjects with ECG evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects
who have a history of acute myocardial infarction within 6 months, or subjects with
unstable angina.