A Study of Carboplatin and Paclitaxel With or Without MEDI-575 in Untreated, Advanced Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the dose, antitumor activity, safety and pharmacology of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer (NSCLC).

This is a Phase 1b/2, multicenter, open-label study of MEDI-575 to evaluate the dose, anti-tumor activity, safety, and pharmacology (pharmacokinetics, immunogenicity, and biomarkers) of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer. This study has two phases: dose determination (Phase 1b) and randomization (Phase 2).

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer according to the Seventh Edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system (only participants with squamous cell carcinoma will be enrolled)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of greater than or equal to (\>=) 3 months
* Prothrombin time elevation less than or equal to (\<=) Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for participants on anticoagulant therapy
* Adequate hematologic function
* Adequate organ function
* Suitable candidates for therapy with carboplatin/paclitaxel
* Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria for Solid Tumors
* Participants must be willing to consent to allow collection of archived NSCLC tumor samples
* Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
* Females of childbearing potential, unless surgically sterile has a sterile male partner, is premenarchal or at least 2 years postmenopausal, or practices abstinence, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) from screening, and must agree to continue using such precautions for 90 days after the final dose of treatment; cessation of birth control after this point should be discussed with a responsible physician
* Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from screening through 90 days after the final dose of treatment

Exclusion Criteria:

* At discretion of the investigator regarding safety of the participants
* Concurrent enrollment in another clinical study
* Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
* Previous monoclonal antibody (mAb) treatment specifically directed against platelet-derived growth factor (PDGF) or PDGF receptors
* History of serious allergy or reaction to any component of the MEDI-575 formulation
* Receipt of any previous systemic anticancer therapies for advanced or metastatic disease
* Previous adjuvant/neoadjuvant radiotherapy or chemotherapy for treatment of previous nonmetastatic disease is allowed provided that 6 months have elapsed from the end of such therapies to the time of enrollment
* New York Heart Association \>= Class II congestive heart failure
* History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
* History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
* Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
* Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
* Systemic immunosuppressive steroid therapy
* Participants may take replacement doses of steroids if on a stable dose for at least 2 weeks prior to enrollment
* History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* Pregnancy or lactation
* Previous medical history or evidence of an inter-current illness
* Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study