Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer

Inclusion Criteria:

* Written informed consent provided prior to any screening procedure
* Male or female, greater than (\>) 18 years of age
* Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
* Demonstrated PD 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 participants must have measurable disease (tumor) without clinically significant pleural effusion 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 World Health Organization (WHO) criteria
* Archived tissue or cytologic sample available for the determination of epidermal growth factor receptor (EGFR) expression
* Eastern cooperative oncology group (ECOG) performance status 0-1
* Life expectancy \>12 weeks
* Adequate baseline organ functions, defined as: Serum creatinine less than or equal to (≤)1.5\*upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be greater than or equal to (≥) 45 millimeters per minute (mL/min); Total bilirubin \<1.5\*ULN; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5\*ULN (participants with liver metastases should have ALT/AST \<5\*ULN.); Absolute neutrophil count ≥1500per cubic millimeter(mm\^3); Platelet count ≥100000/mm\^3; Hemoglobin level ≥10 grams per deciliter
* 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. Participants 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 beta-human chorionic gonadotropin \[β-HCG\]) 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 participant from the study
* History of significant neurologic or psychiatric disorder (for example, 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