Pembrolizumab in Preventing Lung Cancer in Patients With Stage I-II Non-Small Cell Lung Cancer or High-Risk Pulmonary Nodules, the IMPRINT-Lung Study

Inclusion Criteria: 1. Participants with no history of lung cancer, who have IPNs detected by LDCT-guided lung cancer screening or imaging studies for other reasons (incidentalomas) with 10 - 30% cancer probability by Brock University cancer prediction equation as following47. This is one of the most frequently utilized cancer risk prediction equations and has been confirmed to be highly effective in catching the disease in its very early stages by large national studies. 2. Participants with no history of lung cancer, who have IPNs detected by LDCT-guided lung cancer screening or imaging studies for other reasons (incidentalomas) with \> 30% cancer probability by Brock University cancer prediction equation as following, but biopsy reveals no clear evidence of malignancy. 3. Participants with history of stage I-II non-small cell lung cancer (NSCLC), who have completed curative treatment (surgery and/or radiation) with or without chemotherapy, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) with 5-30% cancer probability by Brock University cancer prediction equation as following. 4. Participants with history of stage I-II NSCLC, who have completed curative treatment (surgery and/or radiation) with or without chemotherapy, who have persistent IPNs (on two CT scans at least 3 months apart with no evidence of shrinkage or regression) with \> 30% cancer probability by Brock University cancer prediction equation as following, but biopsy reveals no clear evidence of malignancy. 5. Persistent IPNs with estimated cancer probability ≥ 5% AND at least one of the following criteria i. Emergence of solid components within 12 months before the time of screening for patients with pure GGO nodules OR ii. Enlargement of solid components within 12 months before the time of screening for patients with partial solid nodules OR iii. Enlargement of the overall size of lung nodule leading to increase in predicted risk by 5% within 12 months before the time of screening 2. Male/female participants who are at least 18 years of age on the day of signing informed consent with diagnosis of high-risk IPNs as defined below will be enrolled in this study. 3\. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 12 weeks while receiving pembrolizumab plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period. 4\. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR 2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days for study treatments with risk of genotoxicity after the last dose of study treatment. 5\. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 6\. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of study enrollment. 7\. Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 10 days prior to the start of study treatment. Table 4 Adequate Organ Function Laboratory Values Hematological * Absolute neutrophil count (ANC) = ≥1500 per microliter (within 10 days prior to the start of study treatment). * Platelets = ≥100,000 per microliter (within 10 days prior to the start of study treatment). * Hemoglobin = ≥ 9.0 grams per microliter or = ≥ 5.6 millimoles/liter (within 10 days prior to the start of study treatment) (\*criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks). * Creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCL\]) =≤ 1.5 x ULN OR = ≥ 30 milliliters per minute (min) for participant with creatinine levels \> 1.5 x institutional upper limit of normal (ULN) (creatinine clearance (CrCl) should be calculated per institutional standard.) (within 10 days prior to the start of study treatment). * Total bilirubin = ≤ 1.5 x ULN OR direct bilirubin = ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN (within 10 days prior to the start of study treatment). * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) = ≤ 2.5 x ULN (within 10 days prior to the start of study treatment). * International normalized ratio (INR) OR prothrombin time (PT), activated partial thromboplastin time (aPTT) = ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of study treatment). * PT(INR), aPTT only required for patients having a biopsy and/or if clinically indicated Exclusion Criteria: * Participant has lung diseases currently requiring oxygen supplement. * Participants has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Participant has other lung diseases requiring steroids treatment (10mg of prednisone or equivalent) within 4 weeks at the time of screening. * A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to treatment. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. * Has received prior chest radiotherapy and the radiation field overlaps with IPNs. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has a known additional metastatic malignancy that is progressing or requiring active treatment. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ), or potentially curable early-stage malignancies including localized NSCLC, head and neck squamous carcinoma, breast cancer, bladder cancer etc., that have undergone potentially curative therapy (surgery and/or radiation with or without chemotherapy) are not excluded. * Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has an active infection requiring systemic therapy. * Has a known history of Human Immunodeficiency Virus (HIV). * Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. * Has a known history of active TB (Bacillus Tuberculosis). * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.