Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

- Over 18 years of age

- Participants must have signed and dated a written informed consent form.

- Participants must be willing and able to comply with proposed visit and treatment
schedule.

- Patients with NSCLC documented by histology or cytology from brushing, washing, or
needle aspiration of a defined lesion, but not from sputum cytology alone.

- Patients must have presented at initial diagnosis with Stage III disease according to
American Joint Committee on Cancer (AJCC) Staging Manual, 8th Edition;

- Patients must be deemed by the treating investigator to be surgically unresectable. I

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1

- Patients must initiate study treatment 60 days from the date of pathologic diagnosis.

- Tumor biopsy specimen including at least formalin-fixed, paraffin-embedded (FFPE)
tumor tissue block or 10 unstained slides of tumor sample (archival or recent) for
biomarker evaluation must be available for submission to the central lab for
correlative studies.

- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test within 14 days prior to the start of thoracic radiation therapy.

- Male participants must be willing to refrain from sperm donation during the entire
study and for 5 half-lives of study drug plus 90 days (duration of sperm turnover).

- Investigators shall counsel WOCBP and male participants who are sexually active with
WOCBP on the importance of pregnancy prevention and the implications of an unexpected
pregnancy. Investigators shall advise on the use of highly effective methods of
contraception which have a failure rate of correctly. Azoospermic males are exempt from contraceptive requirements.

- WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with study drug(s) plus 5 half-lives of study drug (half-life up
to 25 days) plus 30 days (duration of ovulatory cycle) for a total of 5 months
post-treatment completion.

- WOCBP who are continuously not heterosexually active are exempt from contraception
requirements. However, they must still undergo pregnancy testing as described in this
section.

- Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with study drug (s) plus 5
half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm
turnover) for a total of 7 months post-treatment completion

Exclusion Criteria:

- All toxicities attributed to prior anti-cancer therapy must have been resolved to
Grade 1 (NCI CTCAE Version 4) or baseline before administration of study drug(s).
Exceptions may apply.

- Women who are pregnant or breastfeeding

- Active, known, or suspected autoimmune disease. Patients with an autoimmune
paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded.
Patients with type I diabetes mellitus, hypothyroidism only requiring hormone
replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring
systemic treatment, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll

- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days of study
initiation. Corticosteroids with minimal systemic absorption (inhaled or topical
steroids) and adrenal replacement steroid doses > 10 mg daily prednisone equivalent
are permitted in the absence of active autoimmune disease

- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody

- Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected drug-related pulmonary toxicity.

- Any patient requiring supplemental oxygen therapy.

- Previous malignancies (except non-melanoma skin cancers, and some in situ cancers)
unless a complete remission was achieved at least 2 years prior to study entry AND no
additional therapy is required during the study period.

- Known medical condition that, in the investigator's opinion, would increase the risk
associated with study participation or study drug(s) administration or interfere with
the interpretation of safety results

- Major surgery or significant traumatic injury that is not recovered at least 14 days
before the initiation of thoracic radiation therapy.

- Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or
positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
antibody test indicating acute or chronic infection. Individuals with a positive test
for HCV antibody but no detection of HCV RNA indicating no current infection are
eligible.

- Known medical history of testing positive for human immunodeficiency virus (HIV) or
known medical history of acquired immunodeficiency syndrome (AIDS)

- Inadequate hematologic function.

- Inadequate hepatic function.

- Inadequate pancreatic function.

- History of allergy or hypersensitivity to any of the study drugs or study drug
components