Low-Dose Interleukin-2 and Pembrolizumab for the Treatment of Stage IV Non-Small Cell Lung Cancer

Inclusion Criteria: 1. Patients must have Stage IV non-small cell lung cancer (NSCLC), based on the 8th edition of the American Joint Committee on Cancer (AJCC) NSCLC Staging System. This includes adenocarcinoma and squamous cell carcinoma. 2. Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. 3. No prior therapy for advanced NSCLC. 4. Patients with brain metastasis are eligible if they are asymptomatic or treated and stable. 5. Age greater than or equal to 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 7. Life expectancy of greater than 12 weeks. 8. Patients must have adequate organ and marrow function, including: 1. Absolute neutrophil count (ANC) ≥ 1,500/mcL 2. Platelet count ≥ 100,000/mcL 3. Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this) 4. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal (ULN) 5. Serum bilirubin l≤ 1.5 x ULN 6. Creatinine Clearance \> 60 mL/min 9. Patients must have tumor PD-L1 expression of ≥1% (by 22c3 PD-L1 companion testing); patients whose PD-L1 status could not be determined are also eligible. Patients with known PD-L1 of 0% will be excluded. 10. For women of childbearing potential or men with sexual partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 5 months after the last dose of study treatment. 1. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). 2. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 11. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: 12. Any prior chemotherapy or immunotherapy for advanced lung cancer. 13. Prior treatment with anti-PD-1 or anti-PD-L1 therapies or pathway-targeting agents. 14. Any targetable driver mutation (e.g. ALK, EGFR exon 19 del, etc). 15. Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation. 16. Major surgical procedure within 28 days prior to cycle 1, day 1. 17. Evidence of visceral crisis (severe organ dysfunction as assessed by signs, symptoms, and laboratory values, resulting from rapid progression of neoplastic disease). 18. Active concomitant malignancy that requires therapy. 19. Treatment with systemic immunosuppressive medications (e.g., prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Cycle 1, Day 1. 1. Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or premedication for contrast dye allergy) are eligible. 2. The use of inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. 20. History or risk 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, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis 1. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible. 2. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible. 3. Patients with eczema, psoriasis, or lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible provided they meet the following conditions: * Rash must cover \< 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 (requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids) 21. 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 CT scan. 22. QTc of \>470 msec by EKG. 23. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease. 24. Known HIV infection. 25. Active tuberculosis. 26. Administration of a live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks before Cycle 1, Day 1 or at any time during the study. 27. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. 28. Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer). 29. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 30. Patients who are pregnant or lactating, or who are intending to become pregnant during the study. 1. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.