MK-3475 and Stereotactic Body Radiation Therapy (SBRT) in Patients With Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

1. Pathologically confirmed non-small lung cancer.

2. Stage IV metastatic disease (only during the phase II)

3. At least one thoracic or liver lesion amenable to radiation, for group 5 we need one
area that can safely receive SBRT or WFRT, not restricted to lung or liver sites.

4. At least one additional non-contiguous lesion to the irradiated lesion amenable to
radiographic evaluation

5. Be willing and able to provide written informed consent/assent for the trial

6. Be >/= 18 years of age on day of signing informed consent

7. Have measurable disease based on immune related response criteria (irRC) criteria

8. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale

9. Demonstrate adequate organ function described in inclusion #12 and #13, all screening
labs should be performed within 28 days prior to study registration up to the first
dose of study drug.

10. Patients with brain metastasis will be included as long as they are free of neurologic
symptoms related to metastatic brain lesions and who do not require or receive
systemic corticosteroid therapy in the 14 days prior to beginning MK-3475 therapy

11. Adequate Organ Function Laboratory Values: *Hematological; Absolute neutrophil count
(ANC) >/=1,500 /mcL, Platelets >/=100,000 / mcL, Hemoglobin >/=9 g/dL or >/=5.6 mmol/L
* Renal; Serum creatinine or Measured or calculated creatinine clearance (glomerular
filtration rate [GFR] can also be used in place of creatinine or CrCl) limit of normal (ULN) or >/=60 mL/min for subject with creatinine levels >1.5 X
institutional ULN [Creatinine clearance should be calculated per institutional
standard] *Hepatic; Serum total bilirubin subjects with total bilirubin levels >1.5 ULN, aspartate aminotransferase (AST) serum
glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum
glutamic-pyruvic transaminase (SGPT) liver metastases

12. Inclusion #12 continued: *Coagulation; International Normalized Ratio (INR) or
Prothrombin Time (PT) as long as PT or PTT is within therapeutic range of intended use of anticoagulants,
Activated Partial Thromboplastin Time (aPTT) anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants

13. Female subject of childbearing potential should have a negative urine or serum
pregnancy 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.

14. Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year.

15. Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study therapy.

16. We will allow XRT prior to study entry to other sites, with no washout period, prior
to study entry as long as at least one measurable sites of disease is kept
unirradiated.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational
agent (except glutamine) or using an investigational device within 4 weeks of the
first dose of treatment or 5 half-lives, whichever is shorter.

2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. Unless the steroid therapy is for physiological replacement.

3. Has a diagnosis of active scleroderma, lupus, or other autoimmune disease which by the
opinion of the treating radiation oncologist precludes safe radiation therapy.

4. Has had prior radiation therapy to all available thoracic and liver lesions such that
additional radiation therapy is unsafe by the opinion of the treating radiation
oncologist.

5. Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, which ever is
shorter, prior to study Day 1 or who has not recovered (i.e., baseline) from adverse events due to agents administered more than 4 weeks earlier.

6. Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to
study Day 1 or who has not recovered (i.e., events due to a previously administered agent. *Note: Subjects with neuropathy are an exception to this criterion and may qualify for the study. **Note:
If subject received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.

7. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.

8. Has 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 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.

9. Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
resolved childhood asthma/atopy would be an exception to this rule. Subjects that
require intermittent use of bronchodilators or local steroid injections would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
Sjorgen's syndrome will not be excluded from the study.

10. Has evidence of interstitial lung disease or active, non-infectious pneumonitis

11. Has an active infection requiring systemic therapy or hospital admission

12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.

13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

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

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

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

17. Has received a live vaccine within 30 days prior to the first dose of trial treatment

18. Symptomatic brain metastasis

19. Has experienced a dose limiting toxicity on treatment with either prior radiation or
anti PD-1 or PD-L1 inhibitor therapy