Inclusion Criteria:

- Known or suspected diagnosis of operable NSCLC that has not been previously treated

- Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or
bronchoscopic

- Able to understand and sign an informed consent discussing the risks and benefits of
obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy
available secondary to institutional tissue collection protocols may substitute such
a biopsy for the study-required pre-treatment biopsy

- Appropriate candidate for surgical management, in the opinion of the treating
thoracic surgeon

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at the time of
initiation of neoadjuvant epigenetic therapy

- Absolute neutrophil count > 1,000/mcL

- Platelets > 100,000/mcL

- Total bilirubin < 1.5 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
< 2.5 x institutional ULN

- Creatinine < 1.5 x institutional ULN

- Able to understand and sign an informed consent

- The effects of entinostat and 5-azacitidine on the developing human fetus at the
recommended therapeutic dose are unknown; for this reason, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Inclusion of women and minorities:

- Both men and women and members of all races and ethnic groups are eligible for
this trial; the coordinating center will be responsible for ensuring each
participating site is accruing a representative sample consistent with the
estimate of population representation in the site's geographical location for
race and ethnic groups as determined by the Census Bureau to assure overall
target goals are met

- Clinical stage IA-IIIA

Exclusion Criteria:

- Patients who have received prior chemotherapy or radiation for their diagnosis of
lung cancer

- Patients may not be receiving any other investigational agent

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to entinostat or 5-azacytidine

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because entinostat and 5-Azacitidine are
agents with the potential for teratogenic or abortifacient effects; because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with entinostat or 5-Azacytidine, breastfeeding should be
discontinued if the mother is treated on this protocol

- Any co-morbid condition that' in the view of the attending physician' renders the
patient at high risk from treatment complications

- Human immunodeficiency virus (HIV) positive patients on combination antiretroviral
therapy are ineligible due to the potential for pharmacokinetic interactions with
entinostat or 5-azacytidine

- Known or suspected hypersensitivity to azacitidine or mannitol

- Patients with advanced malignant hepatic tumors

- Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy,
including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer
therapy, is not permitted while participating in this study; Note: study participants
with stage II or III NSCLC, or stage I NSCLC with tumor size greater than 4 cm,
should be offered standard adjuvant platinum-based chemotherapy in accordance with
local practice (post-operatively)