Randomized, Phase II,Open-Label Controlled Study of Two Different Doses and Schedules of EMD 72000 (Matuzumab) in Combination With Pemetrexed, or Pemetrexed Alone, as Second-Line Treatment for Stage IIIB/IV Non-Small Cell Lung Cancer and Progressive Disease on or After First-Line Treatment With a Platinum in Combination With Taxanes, Gemcitabine and Vinorelbine

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