A Study of Carboplatin and Pemetrexed Plus Demcizumab (OMP-21M18) in Subjects With Non-Squamous Non-Small Cell Lung Cancer

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.