Phase II Clinical Trial of NIVO-IPI-TAXANE in Untreated Metastatic NSCLC

Inclusion Criteria: * Histologically confirmed Stage IV or recurrent Non-small cell lung cancer squamous or non-squamous histology (Stage IV as diagnosed using the 7th edition of Lung Cancer Stage Classification), with no prior systemic anticancer therapy given as primary therapy for advanced or metastatic disease. Prior adjuvant chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy is permitted as long as the last administration of the prior regimen occurred at least 6 months prior to study enrollment. Patients with EGFR, ALK, or ROS1 alterations must have received one prior TKI. * A core needle biopsy or surgical specimen must be available for submission. * At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been previously irradiated; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. * Age ≥ 18 years with ability and willingness to provide informed consent. * ECOG performance status 0 or 1. * Negative pregnancy test done ≤72 hours (or per institutional policy) prior to treatment, for women of childbearing potential only. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: 1. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. 2. Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution 3. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation * Men and women of childbearing potential must agree to use medically accepted barrier methods of contraception (e.g. male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of study and for 90 days after the last dose of study drug. * A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy. * Provision of written informed consent including HIPAA according to institutional guidelines prior to any study-specific procedures * Patients must agree to research blood sampling to participate in study; * Adequate organ and marrow function as defined by the following: 1. Creatinine clearance ≥ 50 cc/min or serum Cr \< 1.5 x institutional ULN 2. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) 3. AST/ALT ≤ 2 x ULN without liver metastasis; ≤ 5 x ULN with liver metastasis 4. Absolute neutrophil count (ANC) ≥ 1500 µl 5. Hemoglobin (Hgb) ≥ 9 g/dL 6. Platelets ≥ 100,000/µl Exclusion Criteria: * Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy and must have received treatment with at least one prior tyrosine kinase inhibitor (TKI). * Subjects with known ALK or ROS1 translocations which are sensitive to available targeted inhibitor therapy must have received treatment with at least one prior TKI. * Radiation therapy within 14 days prior to day 1 of study drug. * Experimental agents within 28 days prior to day 1 of study drug. * Intolerance of nivolumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents. * Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone \< 10 mg daily (or equivalent). * History of interstitial pneumonitis from any cause. * Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease. * Pregnant or breast feeding. * Not willing to use an effective method of birth control medically accepted barrier methods of contraception (e.g. male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug. * Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to day 1 of study drug. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. * Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on day 1 of study drug. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible. * Known active CNS metastases which are symptomatic. Eligible if metastases have been locally treated 14 days prior to cycle 1 day 1, are clinically controlled, or asymptomatic on cycle 1 day * Steroid dose must be equivalent of \<10 mg prednisone daily or equivalent dose steroid. Untreated, asymptomatic brain metastases allowed if subject does not require corticosteroids or anticonvulsant therapy. * History of myocardial infarction, NYHA class III or IV congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment. * Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), hepatitis C virus (allowed if received curative therapy), acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment. * Inability to comply with protocol or study procedures.