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

Inclusion Criteria

1. Age 18 years or older (20 years or older for subjects in the Japanese cohort) at the time of screening
2. Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
3. 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 subjects with squamous cell carcinoma will be enrolled)
4. ECOG PS of 0 or 1 (see, Appendix 2)
5. Life expectancy of ≥ 3 months
6. Prothrombin time elevation ≤ Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for subjects on anticoagulant therapy
7. Adequate hematologic function defined as:
8. Hemoglobin ≥ 9 g/dL
9. Absolute neutrophil count (ANC) ≥ 1500/mm3
10. Platelet count ≥ 100,000/mm3
11. Adequate organ function defined as follows:

12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

    ≤ 5 × institutional upper limit of normal (ULN) for cases involving liver metastasis and ≤ 2 × institutional ULN for all other cases

13. Bilirubin ≤ 1.5 × ULN except in the case of subjects with documented or suspected Gilbert's disease ≤ 5 × ULN
14. Calculated creatinine clearance (CrCl) ≥ 50 mL/min as determined by the Cockroft-Gault equation (Cockroft and Gault, 1976)
15. Suitable candidates for therapy with carboplatin/paclitaxel
16. Subjects must have at least 1 lesion that is measurable using RECIST (v1.1). Other nonmeasurable lesions are allowed.
17. Subjects must be willing to consent to allow collection of archived NSCLC tumor samples
18. Negative serum beta-human chorionic gonadotropin (β-hCG) test (women of childbearing potential only)
19. Females of childbearing potential, unless surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), 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
20. 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
21. Normal potassium at baseline
22. Normal magnesium at baseline

Exclusion Critieria

Any of the following would exclude the subject from participation in the study:

1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the treatment or interpretation of subject safety or study results
2. Concurrent enrollment in another clinical study
3. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
4. Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
5. Previous mAb treatment specifically directed against PDGF or PDGF receptors
6. History of serious allergy or reaction to any component of the MEDI-575 formulation
7. Receipt of any previous systemic anticancer therapies for advanced or metastatic disease including chemotherapy regimens, hormonal therapy, TKIs, radiotherapy, investigational agents, or any biological or immunological based therapies (including, but not limited to mAb therapy such as bevacizumab)
8. 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.
9. New York Heart Association ≥ Class II congestive heart failure (see Appendix 3) MedImmune Protocol CD-ON-MEDI-575-1031
10. History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
11. History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), nonmelanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
12. Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
13. Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
14. Systemic immunosuppressive steroid therapy. Subjects may take replacement doses of steroids (defined as ≤ 30 mg day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to enrollment
15. History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
16. Pregnancy or lactation
17. Previous medical history or evidence of an intercurrent illness that may, in the opinion of the investigator, compromise the safety of the subject in the study
18. Clinically significant abnormality on ECG
19. Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study