To find the optimal dose of afatinib and nimotuzumab in patients who acquired resistance to gefitinib or erlotinib.

Inclusion Criteria:

• Histologically confirmed diagnosis of stage IIIB or IV NSCLC
• Presence of EGFR sensitizing mutations (L858R mutation in exon 21 or exon 19 deletion) or response by RECIST on prior gefitinib or erlotinib or stable disease on prior gefitinib or erlotinib for at least 6 months
• Disease progression on treatemtn with gefitinib or erlotinib within 30 days
• Biopsy on disease progression
• Age ≥20 years
• ECOG performance status of 0, 1, or 2
• Measurable disease by the criteria of RECIST 1.1
• Adequate organ function as evidenced by the following; Absolute neutrophil count > 1.5 x 109/L; platelets > 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT < 5 UNL; creatinine clearance ≥ 45 mL/min

Exclusion Criteria:

• Known interstitial lung disease
• Prior treatment with EGFR targeting antibodies or BIBW 2992
• Prior three or more lines of chemotherapy for advanced NSCLC
• Significant bowel disease impairing drug absorption
• Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
• Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and corticosteroid use has been discontinued for at least 2 weeks prior to the first dose of study drug. Screening of asymptomatic patients without history of CNS metastases is not required.