Cisplatin and Etoposide Plus Radiation Followed By Nivolumab/Placebo For Locally Advanced NSCLC

Inclusion Criteria:

   - Pathologically (histologically or cytologically) proven diagnosis of non-small cell
   lung cancer (NSCLC) with unresectable, medically inoperable disease, or patients who
   refuse resection stage IIIA or stage IIIB disease (AJCC 7th edition)

   - History/physical examination within 30 days prior to registration

   - Computed tomography (CT) scan with IV contrast (CT scan without contrast acceptable if
   IV contrast is medically contraindicated) of the lung and upper abdomen through the
   adrenal glands within 60 days prior to registration (recommended within 30 days prior
   to registration)

   - Magnetic resonance imaging (MRI) of the brain with contrast (or CT with contrast if
   MRI is medically contraindicated) within 60 days prior to registration; note: the use
   of intravenous contrast is required for the MRI or CT (unless medically
   contra-indicated).

   - Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT within 60
   days prior to registration; Note: patients do not need to have a separate CT of chest
   and upper abdomen with contrast if PET/CT imaging includes a high quality CT chest
   with contrast.

   - Age ≥ 18 years

   - The trial is open to both genders

   - Zubrod Performance status of 0-1

   - Forced Expiratory Volume at one second (FEV1) > 1.2 liters; Diffusion Capacity of Lung
   for Carbon Monoxide (DLCO) ≥ 50% predicted

   - Patients must be at least 3 weeks from prior thoracotomy (if performed); if prior
   thoracotomy then measurable disease on imaging must be present

   - Negative serum pregnancy test within three days prior to registration for women of
   childbearing potential

   - An archived tumor block or punches instead block must be available for submission for
   programmed death-ligand 1 (PD-L1) analysis. If an archived tumor block sample cannot
   be shipped for this study, then two 3mm punches from the core needle biopsy blocks may
   be provided for analysis. Note: core or excisional biopsy is required for this study.
   Fine needle aspirates (FNA) and cytology specimens are not adequate for PD-L1
   analysis.

   - Agreement of women of childbearing potential to use highly effective contraception
   during receipt of study drug and up to 161 days (23 weeks) from the last dose of
   nivolumab/placebo and men receiving nivolumab/placebo who are sexually active with
   women of childbearing potential to use highly effective contraception during receipt
   of study drug for 31 weeks from the last dose of nivolumab/placebo.

Exclusion Criteria:

   - Definitive clinical or radiological evidence of metastatic disease

   - Prior or current invasive malignancy (except non-melanomatous skin cancer, localized
   bladder and prostate cancer) unless disease free for a minimum of 2 years (for
   example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)

   - Prior radiotherapy to the region of the study cancer that would result in overlap of
   radiation therapy fields. For example, patients with prior breast radiotherapy
   treatments would likely be excluded.

   - Prior systemic treatment with and anti-programmed cell death protein 1 (PD1),
   anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
   (antibody, or any other antibody or drug specifically targeting T-cell costimulation
   or immune checkpoint pathways

   - Known immunosuppressive disease, for example HIV infection or history of bone marrow
   transplant or chronic lymphocytic leukemia (CLL)

   - Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness
   requiring hospitalization or precluding study therapy at the time of registration.
   COPD requiring chronic oral steroid therapy

   - Unstable angina and/or congestive heart failure requiring hospitalization within the
   last 6 months

   - Transmural myocardial infarction within the last 6 months

   - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
   registration

   - History of symptomatic or p previously established interstitial lung disease

   - Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
   ribonucleic acid (HCV antibody) indicating acute or chronic infection;

   - History of severe hypersensitivity reaction to any monoclonal antibody or allergy to
   study drug components

   - As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition
   to hepatotoxicity should be used with caution in patients treated with
   nivolumab-containing regimen

   - Pregnancy, nursing females or women of childbearing potential and men who are sexually
   active and not willing/able to use medically acceptable forms of contraception; this
   exclusion is necessary because the treatment involved in this study may be
   significantly teratogenic.