Ipilimumab and Nivolumab in Combination With Radiation Therapy in Treating Patients With Stage 2-3 Non-small Lung Cancer

Inclusion Criteria

• •Patients must have histologically or cytologically confirmed NSCLC (any histology)
• •Patients must have stage II or III local-regionally advanced NSCLC that is deemed to be best treated by systemic and concurrent radiotherapy. Eligible patients with stage II disease must be unresectable or refuse surgical resection
• •No prior therapy for the current stage II or stage III NSCLC disease
• •ECOG (Eastern Cooperative Oncology Group) performance status =\< 2 (Karnofsky \>= 60%)
• •Leukocytes \>= 2,000/mcL
• •Absolute neutrophil count \>= 1,000/mcL
• •Platelets \>= 75,000/mcL
• •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN
• •Creatinine =\< 1.5 x institutional ULN
• •Glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• •No prior history of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune vasculitis, or glomerulonephritis
• •* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
• •* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
• •* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• •* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
• •* Rash must cover less than 10% of body surface area (BSA)
• •* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
• •* No acute exacerbations of underlying condition within the last 12 months (not requiring PUVA \[psoralen plus ultraviolet A radiation\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
• •No prior history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computerized tomography (CT) scan
• •No active pregnancy. The effects of ipilimumab-nivolumab on the developing human fetus are unknown. For this reason and because radiation and possibly immunotherapies used in this trial are known or possibly known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of ipilimumab-nivolumab administration
• •Ability to understand and the willingness to sign a written informed consent document
• •Patients with known epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement are eligible