Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy

Inclusion Criteria:

• Subjects with stage IV NSCLC (not recurrent or re-staged).
• Expected to receive at least 2 additional cycles (at least 6 total weeks) of firstline myelosuppressive cyclic chemotherapy after randomization. Subjects should not beexpected to receive only maintenance chemotherapy.
• Eastern Cooperative Oncology Group performance status of 0 or 1 as assessed within 21days prior to randomization.
• 18 years of age or older at screening.
• Life expectancy greater than 6 months based on the judgment of the investigator anddocumented during screening.
• Hemoglobin level less than or equal to 11.0 g/dL as assessed by the local laboratory;sample obtained within 7 days prior to randomization (retest in screening isacceptable).
• Adequate serum folate (greater than or equal to 2 ng/mL) and vitamin B12 (greater thanor equal to 200 pg/mL) levels assessed by central laboratory (supplementation andretest acceptable) during screening.
• Subjects must have had a baseline scan (computed tomography [CT], magnetic resonanceimaging [MRI], or positron emission tomography-computer tomography [PET/CT]) of thechest to assess disease burden before starting on first line chemotherapy for NSCLCand those images must have been reviewed by the investigator prior to randomization.If the scan was performed more than 28 days prior to randomization, an additional scanmust be performed and reviewed by the investigator to confirm that the patient has notprogressed before randomization.
• Before any study-specific procedure, the appropriate written informed consent must beobtained from the subject or a legally accepted representative.

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 ofcuratively resected non-melanomatous skin cancer, curatively treated cervicalcarcinoma in situ, or other primary solid tumors curatively treated with no knownactive disease present and no curative treatment administered for the last 3 years.
• Received any prior adjuvant or neoadjuvant therapy for NSCLC.
• Subjects with a history of brain metastasis.
• Uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg or diastolic BP > 100 mmHg), or as determined by the investigator during screening.
• History of neutralizing antibody activity to recombinant human erythropoietin (rHuEPO)or darbepoetin alfa.
• Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia asdetermined by the investigator at screening. Subjects with known myocardial infarctionwithin 6 months prior to randomization.
• Subjects with a history of seizure disorder taking anti-seizure medication within 30days prior to randomization.
• Clinically significant systemic infection or uncontrolled chronic inflammatory disease (eg, rheumatoid arthritis, inflammatory bowel disease) as determined by theinvestigator during screening.
• Known seropositivity for human immunodeficiency virus (HIV) or diagnosis of acquiredimmunodeficiency syndrome (AIDS), positive for hepatitis B surface antigen, orseropositive for hepatitis C virus
• History of pure red cell aplasia
• History of deep venous thrombosis or embolic event (eg, pulmonary embolism) within 6months prior to randomization.
• Transferrin saturation < 20% and ferritin < 50 ng/mL as assessed by the centrallaboratory during screening. Subjects must have both to be excluded (supplementationand retest acceptable).
• Abnormal renal function (serum creatinine level > 2X upper limit of normal [ULN]) asassessed by the central laboratory during screening.
• Abnormal liver function (total bilirubin > 2X ULN or liver enzymes alanineaminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5X ULN for subjectswithout liver metastasis or ≥ 5X ULN for subjects with liver metastasis) as assessedby the central laboratory during screening. Subjects with documented Gilbert's Diseasemay be eligible.
• Received any red blood cell (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 erythropoiesis stimulating agents (ESAs) (eg,rHuEPO, darbepoetin alfa).
• ESA therapy within the 28 days prior to randomization.
• Known hypersensitivity to recombinant ESAs or the excipients contained within theinvestigational product.
• Less than 30 days since receipt of any investigational product or device.Investigational use/receipt of a medicinal product or device that has been approved bythe country's local regulatory authority for any indication is permitted.
• Subjects of reproductive potential who are pregnant, breast feeding or not willing touse effective contraceptive precautions during the study and for at least one monthafter the last dose of investigational product in the judgment of the investigator (including females of childbearing potential who are partners of male subjects).
• Previously randomized to this study.
• Investigator has concerns regarding the ability of the subject to give writteninformed consent and/or to comply with study procedures (including availability forfollow up visits).