A Therapeutic Trial of Afatinib in the Neoadjuvant Setting. Molecular Effects of Afatinib: A Window of Opportunity Trial In Early Stage NSCLC

Inclusion Criteria:

- Histologically confirmed NSCLC, who are deemed to be surgical candidates by standard
criteria. Patients with all histologies will be allowed to enroll.

Patients with Stage IA to IIIA disease

- ECOG Performance Status 0-1

- Measurable disease by RECIST 1.1 criteria

- Mediastinoscopy and/or Endoscopic Bronchial Ultrasound (EBUS) and/or Endoscopic
Ultrasound (EUS) for complete surgical staging when clinically indicated

- Total bilirubin ≤1.5 mg/dl, SGOT (AST) and SGPT (ALT)≥ 3 x ULN

- Serum creatinine ≤ 1.5 mg/dl

- Serious, active infections must be controlled. Patients may be enrolled while still
on antibiotics as long as clinical signs of active infection have resolved.

- A signed informed consent document (ICD)

- Patients 18 years or older

- Able and willing to take oral medications

Exclusion Criteria:

- Known preexisting lung disease.

- History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure NYHA classification of 3,
unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6
months prior to randomization.

- Significant or recent acute gastrointestinal disorders with diarrhea as a major
symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhea of any etiology.

- Baseline (<1 month before treatment) cardiac left ventricular function with resting
ejection fraction of less than 50% measured by multigated blood pool imaging of the
heart (MUGA scan) or echocardiogram

- Patients may not be receiving any other investigational agents.

- History of allergic reactions to anilinoquinazolins like gefitinib, erlotinib or BIBW
2992

- Uncontrolled intercurrent illness that would preclude a patient from undergoing
surgery

- Psychiatric illness/social situations that would limit compliance with study
requirements.

- Pregnant (positive pregnancy test) or lactating

- Inability to comply with study and/or follow-up procedures

- Patients who are not surgical candidates or refuse surgery