Inclusion Criteria: Subjects must satisfy the following criteria to be randomized in the
1. Age 18 years the time of signing the Informed Consent Form (ICF).
2. Understand and voluntarily provide written informed consent prior to the conduct of
any study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements
4. Histologically or cytologically confirmed advanced nonsquamous NSCLC.
5. No other current active malignancy requiring anticancer therapy.
6. Radiographically documented measurable disease (defined by the presence of 1
radiographically documented measurable lesion).
7. One prior platinum-containing chemotherapy for the treatment of advanced disease.
8. Absolute neutrophil count (ANC) 1500 cells/mm3.
9. Platelets 100,000 cells/mm3.
10. Hemoglobin (Hgb) 9 g/dL.
11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and
alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) 2.5 upper
limit of normal range (ULN) or 5.0 ULN if liver metastases.
12. Total bilirubin 1.5 ULN (unless there is a known history of Gilberts Syndrome).
13. Serum creatinine 1.5 x ULN, or calculated creatinine clearance 60 mL/min (if
renal impairment is suspected 24-hour urine collection for measurement is required).
14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15. Females of childbearing potential [defined as a sexually mature woman who (1) have
not undergone hysterectomy (the surgical removal of the uterus) or bilateral
oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally
postmenopausal for at least 24 consecutive months (ie, has had menses at any time
during the preceding 24 consecutive months)] must:
1. Have a negative pregnancy test (-hCG) as verified by the study doctor within 72
hours prior to starting study therapy. She must agree to ongoing pregnancy
testing during the course of the study, and after end of study therapy. This
applies even if the subject practices true abstinence* from heterosexual
2. Either commit to true abstinence* from heterosexual contact (which must be
reviewed on a monthly basis) or agree to use, and be able to comply with,
effective contraception without interruption, 28 days prior to starting
investigational product (IP), during the study therapy (including dose
interruptions), and for 3 months after discontinuation of study therapy.
Male subjects must:
a. Practice true abstinence* or agree to use a condom during sexual contact with a
pregnant female or a female of childbearing potential while participating in the
study, during dose interruptions and for at least 6 months following IP
discontinuation, even if he has undergone a successful vasectomy.
16. Females must abstain from breastfeeding during study participation and 3 months after
- The presence of any of the following will exclude a subject from enrollment:
1. Squamous cell NSCLC.
2. Prior taxane therapy.
3. Evidence of active brain metastases, including leptomeningeal involvement (prior
evidence of brain metastasis are permitted only if asymptomatic and clinically
stable for at least 8 weeks following completion of therapy). MRI of the brain
(or CT scan w/contrast) is preferred.
4. Only evidence of disease is non-measurable.
5. Known EGFR mutation.
6. Known EML4-ALK mutation.
7. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9. Current congestive heart failure (New York Heart Association Class II-IV).
10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial
infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass
graft, New York Heart Association (NYHA) Class III-IV heart failure,
uncontrolled hypertension, clinically significant cardiac dysrhythmia or
clinically significant electrocardiogram (ECG) abnormality, cerebrovascular
accident, transient ischemic attack, or seizure disorder.
11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human
immunodeficiency virus (HIV) infection, or receiving immunosuppressive or
myelosuppressive medications that would in the opinion of the investigator,
increase the risk of serious neutropenic complications.
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
therapy, defined as ongoing signs/symptoms related to the infection without
improvement despite appropriate antibiotics, antiviral therapy, and/or other
13. History of interstitial lung disease, sarcoidosis, silicosis, idiopathic
pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis.
14. Subject has a clinically significant malabsorption syndrome, persistent
diarrhea, or known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite
15. Treatment with any investigational product within 28 days prior to signing the
16. History of or suspected allergy to nab-paclitaxel, azacitidine, human albumin or
17. Currently enrolled in any other clinical protocol or investigational trial that
involves administration of experimental therapy and/or therapeutic devices.
18. Any other clinically significant medical condition, psychiatric illness, and/or
organ dysfunction that will interfere with the administration of the therapy
according to this protocol or which, in the views of investigator, preclude
19. Any other malignancy within 5 years prior to randomization, or advanced
malignant hepatic tumors, with the exception of adequately treated squamous cell
carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous
skin cancer, carcinoma in situ of the breast, or incidental histological finding
of prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a
or T1b). (All treatment of which should have been completed 6 months prior to
20. Any condition including the presence of laboratory abnormalities, which places
the subject at unacceptable risk if he/she were to participate in the study.
21. Any medical condition that confounds the ability to interpret data from the
22. Pregnant or breastfeeding females.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both