A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer

Inclusion Criteria

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