MPDL3280A and Stereotactic Ablative Radiotherapy in Patients With Non-small Cell Lung Cancer

Inclusion Criteria:

* Signed informed consent
* Ability to comply with the protocol
* Adults with histologically proven stage IV non-small cell lung cancer
* At least two sites of measurable disease as defined by RECIST 1.1; one of which must be amenable to treatment with SAR and accessible for optional pre- and post- treatment biopsy; if a pulmonary nodule is being considered for SAR it must range in size from 1-3 cm
* Have provided written consent for mandatory pre- and post-treatment biopsy (expansion cohort only)
* Patients with treated supratentorial metastases are allowed if stable, the patient is off steroids and no evidence of intracranial hemorrhage
* Archival tumor sample available; a minimum of 10 unstained slides; no fine needle aspiration (FNAs) allowed or tumor tissue from bone
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Life expectancy \>= 3 months
* Absolute neutrophil count (ANC) \>= 1500 cells/ul
* White blood cell (WBC) count \> 2500/uL
* Lymphocyte count \>= 500/uL
* Platelet count \>= 100,000/uL
* Hemoglobin \>= 9 g/dL
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN) with alkaline phosphatase =\< 2.5 x ULN OR AST and ALT =\< 1.5 x ULN, with alkaline phosphatase \> 2.5 x ULN
* Serum bilirubin =\< 1.0 x ULN
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to randomization)
* Creatinine clearance \>= 30 mL/min by Cockcroft-Gault formula
* No history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
* No other active malignancy
* No active autoimmune disease or a history of known or suspected autoimmune disease
* No chemotherapy or radiotherapy within the past 28 days and patients must have recovered any acute toxicity associated with their most recent previous treatment
* Any number of prior treatments is allowed; must have failed at least 1 treatment regimen for metastatic disease
* Female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception

Exclusion Criteria:

* Patients whose tumors contain activating epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement should be excluded from this study, unless disease has progressed on all available, approved therapies targeting the EGFR mutation or ALK rearrangement
* Active or untreated central nervous system (CNS) metastases
* Leptomeningeal disease
* Uncontrolled pleural or pericardial effusion or ascites that would require recurrent drainage
* Uncontrolled tumor related pain
* Uncontrolled hypercalcemia
* Pregnant and lactating women
* Uncontrolled concomitant disease
* Significant cardiovascular disease (New York Heart Association class II or greater); myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina or a patient with a known left ventricular ejection fraction (LVEF) \< 40%
* Severe infection within 4 weeks prior to enrollment
* Oral or IV antibiotics within 2 weeks prior to enrollment
* History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the MDPL3280A formulation
* History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis

  * Patients with a history of autoimmune-related 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 a prior allogeneic bone marrow transplantation or prior solid organ transplantation
* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan

  * A history of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Positive test for human immunodeficiency virus (HIV)
* Patients with active hepatitis B (defined as a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C

  * Patients with past hepatitis B virus infection or resolved hepatitis B virus (HBV) infection (defined as a negative HBSAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible
  * Patients with a hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
* Active tuberculosis
* Administration of a live, attenuated vaccine within 4 weeks prior to enrollment or anticipation that such a live attenuated vaccine will be required during the study
* Prior treatment with a cluster of differentiation (CD)137 agonists, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-programmed cell death 1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway targeting agents
* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrollment
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 2 weeks prior to enrollment or anticipated requirement for systemic immunosuppressive medications during the trial

  * Patients who have received acute, low dose, systemic immunosuppressant medication (e.g., a one-time dose of dexamethasone for nausea) may be enrolled after a discussion and approval by the principal investigator
  * The use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) is allowed