Inclusion Criteria:

- Patients must have histologically or cytologically proven non-small cell lung cancer.
Tumor tissue must be available from all patients prior to initiation of protocol
therapy, either from original diagnostic biopsy, or biopsy performed prior to
initiation of protocol therapy.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional
techniques or as >10 mm with spiral CT scan, MRI, or calipers by clinical exam. See
Section 11 for the evaluation of measurable disease.

- Patients must have received one prior therapy, and no more than one prior therapy.

- Patients with EGFR mutations in exon 19 or 21 and patients with detected ALK
translocation may have had two prior therapies if one was a tyrosine kinase inhibitor
specific to their mutation.

- Age >18 years.

- ECOG performance status 0-1.

- Life expectancy of greater than 12 weeks.

- Patients must have normal organ and marrow function.

The effects of entinostat and azacitidine on the developing human fetus 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 she or her partner is participating in this study, she
should inform her treating physician immediately.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients who are receiving any other investigational agents.

- Patients with uncontrolled brain metastases. Patients with brain metastases must have
stable neurologic status following local therapy (surgery or radiation) for at least
4 weeks, and must be without neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events. Patients may be treated with
steroids as clinically indicated.

- Patients with liver metastases that replace greater than 30% of the liver parenchyma.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to entinostat, azacitidine, mannitol, irinotecan, docetaxel, Pemetrexed,
or gemcitabine, or other agents used in the study.

- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, NYHA class 3-4 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, azacitidine, and
irinotecan, docetaxel, Pemetrexed, or gemcitabine 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, azacitidine, or irinotecan, docetaxel, Pemetrexed, or gemcitabine
breastfeeding should be discontinued if the mother is treated on this protocol. These
potential risks may also apply to other agents used in this study.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with entinostat, azacitidine, or
irinotecan, docetaxel, Pemetrexed, or gemcitabine. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with entinostat, azacitidine, or
irinotecan, docetaxel, Pemetrexed, or gemcitabine. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.