A Personal Cancer Vaccine (NEO-PV-01) With Pembrolizumab and Chemotherapy for Patients With Lung Cancer

This clinical trial will enroll patients with advanced or metastatic nonsquamous non-small
cell lung carcinoma not having received treatment for metastatic disease. The five agents
being used in this study are:

- A new, investigational, personalized cancer vaccine called "NEO-PV-01"

- Poly-ICLC (Hiltonol), an investigational adjuvant that is used to help stimulate the
immune system

- A cancer drug called pembrolizumab (KEYTRUDA®)

- A chemotherapy called pemetrexed (ALIMPTA®)

- A chemotherapy called carboplatin

Both NEO-PV-01 and pembrolizumab are considered immunotherapies and work using the immune
system to fight cancer. NEO-PV-01 is a custom made vaccine for you that is based on the
specific targets on your cancer. Poly-ICLC is an adjuvant that helps stimulate the immune
system and make the vaccine, NEO-PV-01, more effective.

Pembrolizumab helps T-cells, a certain type of immune cell, that recognize these targets to
reach and attack your cancer. Pembrolizumab, which is approved in the USA and some other
countries, is available by prescription to treat several different cancers, including the
type of cancer that you have. Recently, the FDA also approved the combination of
Pembrolizumab with chemotherapy for the treatment of your type of lung cancer. This
combination works better than each of the drugs on their own.

The purpose of this study is to find out if treatment with NEO-PV-01 in combination with
pembrolizumab and chemotherapy is safe and useful for patients with lung cancer. The study
also will assess if the NEO-PV-01 vaccine, when given together with pembrolizumab and
chemotherapy, can improve your immune response compared with pembrolizumab and chemotherapy
treatment alone. The side effects of NEO-PV-01, pembrolizumab, and chemotherapy will be
monitored and additional research tests will be done to assess your immune response to your
cancer.

Inclusion Criteria:

- Willing and able to give written informed consent.

- Have histologically confirmed unresectable or metastatic nonsquamous NSCLC and having
received no prior systemic therapy for metastatic disease.

- Have at least 1 site of disease measurable by RECIST v1.1 that has not been treated
with local therapy within 6 months of study treatment. Tumor lesions situated in a
previously irradiated area are considered measurable if progression has been
demonstrated in such lesions.

- At least 1 site of disease must be accessible to provide repeat biopsies for tumor
tissue for sequence and immunological analysis. This site may be a target lesion as
long as it will not be made unmeasurable by the biopsy procedure.

- Have ECOG PS of 0 or 1 with an anticipated life expectancy of > 6 months.

- Recovered from all toxicities associated with prior treatment to acceptable baseline
status (for laboratory toxicities see below limits for inclusion) or a National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03,
Grade of 0 or 1, except for toxicities not considered a safety risk (eg, alopecia or
vitiligo).

- Screening laboratory values must meet the following criteria and should be obtained
within 30 days (or 45 days if a biopsy is repeated) prior to study treatment:

1. White blood cell (WBC) count ≥ 3 × 10e3/µL

2. Absolute neutrophil count (ANC) ≥ 1.5 × 10e3/µL

3. Platelet count ≥ 100 × 10e3/µL

4. Hemoglobin > 9 g/dL

5. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance
(CrCl) ≥ 40 mL/min/1.73 m2

6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
or ≤ 5 × ULN for patients with liver metastases

7. Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome who can
have total bilirubin < 3.0 mg/dL). Direct bilirubin ≤ ULN for patients with total
bilirubin levels >1.5 × ULN.

8. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN unless
patient is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants

9. Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN unless patient is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants

- Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required.

- Female patients of childbearing potential must be willing to use an adequate method of
contraception as outlined in Section 6.4.5.3, for the course of the study through 120
days after the last dose of study medication. Abstinence is acceptable if this is the
usual lifestyle and preferred contraception for the patient.

- Male patients of childbearing potential must agree to use an adequate method of
contraception as outlined in Section 6.4.5.3, starting with the first dose of study
therapy through 120 days after the last dose of study therapy. Abstinence is
acceptable if this is the usual lifestyle and preferred contraception for the patient.

Exclusion Criteria:

- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of first dose of treatment.

- Received any systemic therapy for cancer treatment including immunotherapeutic agents
such as anti-PD1 or anti-PD-L1 antibody therapy.

- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (ie, ≤ 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 30 days 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.

1. Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception
to this criterion and may qualify for the study.

2. Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy

- Patients may not receive or have received any radiation therapy at the biopsy sites.

- Received radiation therapy to the lung > 30 Gy within 6 months of first dose of study
treatment.

- Received prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days
of first dose of study treatment.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging (using the identical
imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks
prior to the first dose of trial treatment 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.

- Patients may not receive any non-oncology vaccine therapy during the period of NEO
PV-01 or pembrolizumab administration and until at least 8 weeks after the last dose
of the booster vaccine. Seasonal influenza vaccines are allowed but may not be
administered between the first dose of pembrolizumab and the last booster dose of
NEO-PV-01

- Has received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant
erythropoietin) within 4 weeks prior to study Day 1.

- Has active autoimmune disease that has required systemic treatment in past 2 years
(ie, with use of disease modifying agents, corticosteroids or immunosuppressive
drugs).

- Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic
treatment.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
The use of physiologic doses of corticosteroids may be approved after consultation
with the Sponsor.

- Received a live-virus vaccination within 30 days of planned treatment start.

- Have symptomatic ascites or pleural effusion.

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

- Has a history of interstitial lung disease.

- Has an active infection requiring systemic therapy.

- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

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

- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection requiring treatment, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia.

- Have any underlying medical condition, psychiatric condition, or social situation
that, in the opinion of the Investigator, would compromise study administration as per
protocol or compromise the assessment of AEs.

- Have a planned major surgery.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.

- Nursing women are excluded from this study because there is an unknown but potential
risk of AEs in nursing infants secondary to treatment of the mother with
pembrolizumab, personalized neoantigen peptides, and adjuvant.

- Have a history of an invasive metastatic disease, except for the following:

1. Individuals with a history of invasive metastatic disease are eligible if they
have been disease free for at least 2 years and are deemed by the Investigator to
be at low risk for recurrence of that metastatic disease;

2. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical
cancer.

- Patients with nonsquamous NSCLC having functionally significant anaplastic lymphoma
kinase (ALK) translocations or epidermal growth factor receptor (EGFR) mutations who
have not received prior treatment with ALK or EGFR inhibitor.

- Have severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its
excipients.