Combination of a Personalized Therapeutic Anti-tumor Vaccine With Pembrolizumab in Non-Small Cell Lung Cancer

Inclusion Criteria:

- Histologically confirmed stage IV NSCLC (squamous, adenocarcinoma, or large cell
carcinoma) that is stable after four cycles of a platinum doublet. Maintenance
chemotherapy is not allowed.

- Sufficient tumor tissue must be available for histologic assessment of PD-L1
expression and whole exome sequencing.

- Measurable disease by RECIST 1.1.

- At least 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) OR

- Direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN

- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver
metastases)

- Albumin ≥ 2.5 mg/dL

- Serum creatinine ≤ 1.5 x IULN OR

- Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min/1.73 m2 for patients with
creatinine levels > 1.5 x IULN

- INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long
as PT or *PTT is within therapeutic range of intended use of anticoagulants

- aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT
or PTT is within therapeutic range of intended use of anticoagulants

- Sexually active women of childbearing potential and men must agree to use 2 methods of
contraception (hormonal or barrier method of birth control, abstinence) prior to study
entry, for the duration of study participation, and for 120 days after last dose of
pembrolizumab. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- Treatment with an anti-cancer monoclonal antibody within 4 weeks prior to Day 1 or has
not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier.

- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ grade 1 or at
baseline) from adverse events due to a previously administered agent. Note: subjects
with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the
study. Note: if subject received major surgery, s/he must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to Day 1.

- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

- Prior treatment with a cancer vaccine.

- Prior treatment with an anti-CTLA-4 agent

- Received a live vaccine within 30 days prior to Day 1.

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Subjects with previously treated brain metastases may participate provided they are
stable (without evidence of progression by imaging for at least four weeks prior to
Day 1 and any neurologic symptoms have returned to baseline), have no evidence of new
or enlarging brain metastases, and are not using steroids for at least 7 days prior to
trial treatment. This exception does not include carcinomatous meningitis, which is
excluded regardless of clinical stability.

- Currently receiving any other investigational agents or has participated in a study of
an investigational agent or using an investigational device within 4 weeks prior to
Day 1.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to pembrolizumab or other agents used in the study.

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

- Has an active autoimmune disease requiring systemic treatment within the past 2 years
(i.e. with use of disease modifying agents, corticosteroids (prednisone dose of 5 mg
or less per day is allowed), or immunosuppressive drugs). Replacement therapy (e.g.,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc.) is not considered a form of systemic treatment.

- Known history of, or any evidence of active, non-infectious pneumonitis.

- Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy
test within 72 hours of study entry.

- Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA
[qualitative] is detected).

- Known history of active tuberculosis (TB)

- Known history of HIV (HIV 1/2 antibodies).