Inclusion Criteria

Inclusion Criteria

1. Pathologic confirmation of stage IIIB/IV or relapsed NSCLC (squamous carcinoma,
adenocarcinoma, or large cell carcinoma). Patients with mixed tumors with small- cell
elements are ineligible.

2. At least one lesion that can be accurately measured in at least one dimension
(longest diameter to be recorded) as >20 mm with conventional techniques, or as >10
mm with spiral computerized tomography (CT) scan according to the Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009)

3. Failure of at least 1, and no more than 2, prior chemotherapy regimens for advanced
disease (either due to progressive disease or toxicity).

4. Recovery from any toxic effects of prior therapy to ≤grade 1 per the National Cancer
Institute Common Terminology Criteria for Adverse Events.

5. Completion of radiation therapy at least 28 days prior to the start of study
treatment (not including palliative local radiation). Previously irradiated lesions
in the advanced setting cannot be included as target lesions unless clear tumor
progression has been observed since the end of radiation.

6. An Eastern Cooperative Oncology Group Performance Status of 0-2.

7. Adequate organ system function as defined within the protocol.

8. A female is eligible to enter and participate in this study if she is of
non-childbearing potential or of childbearing potential.

9. Patients entering this study must be willing to provide tissue from previous tumor
biopsy (if available) for correlative tissue testing.

10. Patients ≤18 years of age.

11. Patients must be able to understand the nature of this study, give written informed
consent, and comply with study requirements.

Exclusion Criteria

1. Past or current history of neoplasm (other than the entry diagnosis), with the
exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or
other cancers cured by local therapy alone, and a disease-free survival ≤3 years.

2. Prior treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs) or vascular
endothelial factor receptor tyrosine kinase inhibitors (VEGFR TKIs) for NSCLC. [Note:
prior bevacizumab (Avastin®) use is permitted].

3. Prior use of an investigational agent within 28 days or 5 half-lives, whichever is
longer, prior to the first dose of study drug.

4. History of any one or more of the following cardiovascular conditions within the past
6 months:

• Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary
artery bypass graft surgery, Symptomatic peripheral vascular disease, Class III or IV
congestive heart failure, as defined by the New York Heart Association (NYHA)
classification.

5. History or clinical evidence of CNS metastases or leptomeningeal carcinomatosis,
except for individuals who have previously treated CNS metastases, are asymptomatic,
and have had no requirement for steroids or anti-seizure medication for 1 week prior
to first dose of study drug. Screening with CNS imaging (computerized tomography [CT]
or magnetic resonance imaging [MRI]) is required only if clinically indicated or if
the subject has a history of CNS metastases.

6. Women who are pregnant or lactating. All females of childbearing potential must have
negative serum or urine pregnancy tests within 7 days prior to study treatment.

7. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg
or diastolic blood pressure (DBP) of ≥90mmHg]. [Note: Initiation or adjustment of
antihypertensive medication(s) is permitted prior to study entry. BP must be
re-assessed on two occasions that are separated by a minimum of 1 hour; on each of
these occasions, the mean (of 3 readings) SBP/DBP values from each BP assessment must
be <140/90 mmHg in order for a subject to be eligible for the study.

8. Presence of uncontrolled infection.

9. Prolongation of heart rate-corrected QT interval (QTc) >480 msecs using Bazett's
formula.

10. Use of any of the medications on the prohibited medication list within 14 days of
study treatment (with the exception of Amiodarone, which is prohibited from 6 months
prior to screening through discontinuation from the study).

11. A serious underlying medical condition that would impair the ability of the patient
to receive protocol treatment.

12. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
placement not considered to be major).

13. Minor surgical procedures (with the exception of the placement of portacath or other
central venous access) performed less than 7 days prior to beginning protocol
treatment.

14. History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
months.

15. Patients who have previously received treatment with cetuximab.

16. Patients with hemoptysis or tumor cavitation at baseline.

17. Any prior history of hypertensive crisis or hypertensive encephalopathy.

18. Pulmonary hemorrhage/bleeding event within 6 weeks prior to beginning study
treatment.

19. Any other non-pulmonary hemorrhage/bleeding event ≥grade 3 within 28 days of study
treatment.

20. Evidence or history of bleeding diathesis.

21. Serious non-healing wound, ulcer, or bone fracture.

22. Known or suspected allergy/hypersensitivity to any agent given in the course of this
trial.

23. Clinically significant gastrointestinal abnormalities.

24. Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product.

25. Any condition that impairs the patient's ability to swallow whole pills.

26. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
(Note: tumor abutting the vessels is acceptable, but contiguous tumor and vessels is
not; CT with contrast is strongly recommended to evaluate such lesions).

27. Cavitary lesions deemed to be at increased risk of bleeding.

28. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib and/or erlotinib.