Inclusion Criteria:

• Written informed consent provided prior to any screening procedure
• Male or female,> 18 years of age
• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer
• Demonstrated progressive disease on or after first-line chemotherapy for stage IIIB/IV disease. The first-line therapy must consist of platinum-based regimens in combination with taxanes,gemcitabine or vinorelbine.. Stage IIIB/IV patients must have measurable disease (tumor) without clinically significant pleural unless the pleural effusion can be effectively drained prior to admission into the study.
• A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment
• At least 1 measurable lesion according to the modified WHO criteria
• Archived tissue or cytologic sample available for the determination of EGFR expression
• ECOG performance status 0-1
• Life expectancy >12 weeks
• Adequate baseline organ functions, defined as follows: *Serum creatinine ≤1.5 × upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be ≥45 mL/min; *Total bilirubin <1.5 × ULN; *Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 × ULN (Subjects with liver metastases should have ALT/AST <5 × ULN.); *Absolute neutrophil count ≥1500/mm3; *Platelet count ≥100,000/mm3; *Hemoglobin level ≥10 g/dL11
• If procreative potential (male or female), willingness to use effective contraceptive methods for the duration of treatment and continuing for 2 months after the last dose. Subjects of procreative potential are defined as any fertile male, or any female who has experienced menarche and who is not postmenopausal (defined as age-related amenorrhea ≥12 months) or who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy)

Exclusion Criteria:

• Radiotherapy or major surgery within 30 days prior to the start of study treatment
• Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors
• Prior treatment with pemetrexed
• Pregnant (confirmed by β-HCG) or lactating female
• Weight loss >10% within 12 weeks prior to the start of study treatment
• Documented or symptomatic brain metastases or leptomeningeal disease
• Myocardial infarction within 6 months prior to the start of study treatment, uncontrolled congestive heart failure, or any current New York Heart Association Grade III or IV cardiovascular disorder despite treatment
• Presence of a ≥Grade 2 preexisting skin disorder (except for alopecia)
• Previous diagnosis of autoimmune disease with significant organ involvement
• Concurrent malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
• Any significant disease that, in the Investigator's opinion, should exclude the subject from the study
• History of significant neurologic or psychiatric disorder (e.g., dementia, seizures, or bipolar disorder)
• History of drug abuse within 6 months prior to the start of study treatment
• Known conditions that require concurrent treatment with a nonpermitted drug
• Presence of a contraindication to the study treatment(s) according to the current Investigator's Brochure (IB) for matuzumab and the labeling for pemetrexed
• Known hypersensitivity to the study treatment or any of its components
• Participation in another clinical study within 30 days prior to the start of study treatment