This is a double-blind, randomized, placebo-controlled phase 3 non-inferiority study in subjects with chemotherapy induced anemia receiving multi-cycle chemotherapy for the treatment of metastatic (stage IV) or advanced stage IIIB with malignant pleural effusion NSCLC. Approximately 3000 subjects with metastatic (stage IV) or advanced stage IIIB with malignant pleural effusion NSCLC receiving or about to receive first line chemotherapy will be enrolled into the study. Subjects will be randomized in a 2:1 allocation (Group A: darbepoetin alfa 500 µg Q3W, Group B: placebo Q3W)

• Non-small Cell Lung Cancer
• Anemia
• Cancer
• Lung Cancer

• Drug: darbepoetin alfa 500 mcg Q3W
  darbepoetin alfa 500 mcg (Q3W)
• Drug: placebo
  Placebo

• A: Active Comparator
  darbepoetin alfa 500 µg (Q3W)
  Intervention: Drug: darbepoetin alfa 500 mcg Q3W
• B: Placebo Comparator
  Placebo Q3W
  Intervention: Drug: placebo

Inclusion Criteria:

• Subjects with metastatic (stage IV) or advanced stage IIIB with malignant pleural effusion NSCLC
• Receiving or about to receive first line cyclic chemotherapy for NSCLC and expected to receive at least 2 additional cycles of cyclic chemotherapy
• Eastern Cooperative Oncology Group performance status of 0 or 1 as assessed at screening
• 18 years of age or older at screening
• Life expectancy > 6 months based on the judgment of the investigator and documented at screening
• Subjects with chemotherapy-induced anemia as defined as having a hemoglobin level less than or equal to 11.0 g/dL at screening

Exclusion Criteria:

• Known primary benign or malignant hematologic disorder which can cause anemia
• History of, or current active cancer other than NSCLC, with the exception of curatively resected non-melanomatous skin cancer, curatively treated cervical carcinoma in situ, or other primary solid tumors curatively treated with no known active disease present and no curative treatment administered for the last 3 years
• Subjects with a history of brain metastasis
• Uncontrolled hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg), or as determined by the investigator at screening
• History of neutralizing antibody activity to rHuEPO or darbepoetin alfa
• Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial infarction within 6 months prior to screening
• Subjects with a history of seizure disorder taking anti-seizure medication within 30 days of screening
• Clinically significant systemic infection or uncontrolled chronic inflammatory disease (eg, rheumatoid arthritis, inflammatory bowel disease) at the time of screening as determined by the investigator
• Known seropositivity for HIV or diagnosis of AIDS, positive for hepatitis B surface antigen, or seropositive for hepatitis C virus
• History of pure red cell aplasia
• History of deep venous thrombosis or embolic event (eg, pulmonary embolism) within 6 months prior to screening
• Received any RBC transfusion within 28 days prior to randomization.
• Plan to receive any RBC transfusion between randomization and study day 1
• Known previous treatment failure to ESAs (ie, rHuEPO, darbepoetin alfa)
• ESA therapy within the 28 days prior to screening
• Known hypersensitivity to recombinant ESAs or the excipients contained within the investigational product