Inclusion Criteria:

1. Age ≥18 years.

2. Histologically confirmed non-squamous NSCLC (squamous cell histology is ineligible).
Cytologic specimens obtained by brushings, washings or needle aspiration of the
defined lesion are acceptable. Sputum cytology alone is not acceptable. Mixed
tumors with small cell elements are not eligible.

3. Newly diagnosed unresectable stage IIIB or stage IV disease. Patients with stage
IIIB disease should be ineligible for combined modality therapy (i.e., pleural
effusions, pericardial effusions, etc.).

4. At least one unidimensionally measurable lesion definable by magnetic resonance
imaging (MRI) or computed tomography (CT) scan. Measurable disease is defined by the
Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

5. Demonstration of K-ras wild type in archived tumor tissue. Tissue must be available
for testing or results from previous K-ras testing must be available at the time of
registration.

6. No prior antineoplastic chemotherapy for metastatic lung cancer. Patients may have
received adjuvant treatment for stage I, II or III disease.

7. For patients who have had previous radiotherapy as definitive therapy for locally
advanced NSCLC, recurrence must be outside of the original radiation therapy port.
Radiation therapy must have been completed more than four weeks prior to study entry.
Previous radiation must have covered < 30% of marrow bearing area.

8. Full recovery from surgery for patients who have undergone thoracotomy. Patients
cannot start protocol treatment until at least three weeks after an operative
procedure.

9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

10. Life expectancy ≥ 12 weeks.

11. Normal bone marrow function within 7 days prior to initial treatment as defined by:

- absolute neutrophil count (ANC) ≥1500/µL

- platelets ≥100,000/µL

- hemoglobin ≥8.0 g/dL. Patients may receive transfusions or erythropoietin to
maintain or exceed this level.

12. Normal hepatic function as defined by:

- bilirubin ≤1.5 x institutional upper limit of normal (ULN).

- transaminases ≤2.5 x institutional ULN. In the presence of known hepatic
metastases, transaminases may be ≤5 x institutional ULN.

13. Normal renal function within 7 days prior to initial treatment as defined by:

- serum creatinine <2.0 mg/dL

- estimated creatinine clearance (CrCl) ≥ 45 mL/min calculated by the
Cockcroft-Gault method.

14. Normal metabolic function as follows:

• Magnesium ≥ institutional lower limit of normal (LLN)

15. The ability to take folic acid, vitamin B12, and dexamethasone according to the
protocol.

16. The ability to interrupt non-steroidal anti-inflammatory drugs (NSAIDs) 2 days before
(5 days for long-acting NSAIDs), the day of, and 2 days following administration of
pemetrexed.

17. Negative serum or urine pregnancy test within 7 days prior to initial study
treatment.

18. Agreement of women of child-bearing potential (WOCBP) and men to use adequate
contraception (hormonal or barrier method of birth control; abstinence) to prevent
contraception during treatment and for a minimum of 6 months after the last study
treatment.

19. Willingness and ability to comply with study and follow-up procedures.

20. Ability to understand the nature of this study and give written informed consent.

Exclusion Criteria:

1. NSCLC with squamous cell histology.

2. History of any invasive cancer treated within the previous 5 years with the exception
of the disease under study, curatively treated non melanoma skin cancer or carcinoma
in situ of the cervix.

3. Prior therapy which specifically and directly targets the EGFR pathway (e.g.,
cetuximab, gefitinib, erlotinib, lapatinib).

4. Active brain or meningeal metastases. Patients must have completed any previous
radiotherapy at least four weeks prior to study entry and recovered from any toxicity
associated with radiotherapy. Patients must have no on-going requirement for and
must have discontinued corticosteroids.

5. Pregnancy or breast-feeding.

6. A serious active infection at the time of treatment or other serious underlying
medical condition that would impair the ability of the patient to receive protocol
treatment.

7. Acute hepatitis or known human immunodeficiency virus (HIV) infection.

8. Presence of third space fluid which is clinically significant and cannot be
controlled by drainage.

9. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis or any
evidence of interstitial lung disease on baseline chest CT scan).

10. History of any medical or psychiatric condition or laboratory abnormality that in the
opinion of the investigator may increase the risks associated with the study
participation or investigational product(s) administration or may interfere with the
interpretation of the results.

11. Prior severe infusion reaction to a monoclonal antibody or history of allergic
reactions attributed to compounds of similar chemical or biologic composition to
agents used in study (e.g., carboplatin, pemetrexed).