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

PRIMARY OBJECTIVES:

I. To compare the Overall Survival (OS) for patients with Stage III unresectable non-small
cell lung cancer treated with or without nivolumab following concurrent chemoradiation.

II. To compare Progression-Free Survival (PFS) according to RECIST 1.1 criteria for patients
with Stage III unresectable non-small cell lung cancer treated with or without nivolumab
following concurrent chemoradiation.

Inclusion Criteria:

- Pathologically (histologically or cytologically) proven diagnosis of 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

- 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)

- 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 FDG-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
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-PD1, anti-PD-L1, anti-PD-L2, anti-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.