Pembrolizumab and Itacitinib (INCB039110) for Non-Small Cell Lung Cancer

Inclusion Criteria: * 1\. Stage IV or metastatic non-small cell lung cancer (NSCLC) * 2\. Provide written informed consent for the trial. * 3\. Patients ≥ 18 years of age * 4\. Tumor PD-L1≥ 50% as assessed by the PD-L1 IHC 22C3 pharmDx assay (Dako North America). * 5\. Subject must have adequate tumor burden at a safely accessible site for biopsy. NOTE: If sites chosen for biopsy were previously irradiated, there must be evidence of tumor growth/viable tumor as assessed by the investigator. * 6\. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * 7\. ECOG performance status 0 or 1 * 8\. Adequate Organ Function Laboratory Values: Absolute neutrophil count (ANC) ≥1,250/mcL; Platelets ≥100,000/mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L; Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥50 mL/min for subject with creatinine levels \> 1.5 X institutional ULN; Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases * 9\. Subjects of reproductive potential must agree to use acceptable birth control methods. Exclusion Criteria: * 1\. Sensitizing mutations in Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) or ROS1 proto-oncogene receptor tyrosine kinase (ROS1) translocations * 2\. Currently participating in or has participated in a study of an investigational agent or anticipated use of an investigational device within 4 weeks of the first dose of study treatment. * 3\. Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. * 4\. Received prior systemic cytotoxic chemotherapy, biologic therapy, targeted therapy or immunotherapy for incurable (metastatic) NSCLC. * 5\. Diagnosis of immunodeficiencywithin 7 days prior to eligibility confirmation by the physician-investigator. * 6\. Prior monoclonal antibodies used for the treatment of NSCLC within 4 weeks prior to eligibility confirmation by the physician-investigator, or individuals who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. * 7\. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-invasive bladder tumors, or in situ cervical cancer * 8\. 8. Active autoimmune disease requiring systemic immunosuppressive treatment within the past 3 months prior to eligibility confirmation by the physician-investigator. Subjects that require intermittent use of steroid-containing bronchodilators or local steroid injections or topical steroid medications are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome are not excluded from the study. * 9\. Interstitial lung disease or history of pneumonitis that has required oral or IV steroids * 10\. Active infection requiring systemic therapy with IV antibiotics * 11\. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * 12\. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * 13\. Pregnant or breastfeeding women * 14\. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). * 15\. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * 16\. Known active Hepatitis B (e.g., HBsAg positive or HBV DNA detectable) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * 17\. Anticipated receipt of any live vaccine within 30 days prior to the first dose of trial treatment. Note: For the purposes of determining eligibility above, enrollment is defined as the date of subject consent.