Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer

Diagnosis/Condition for Entry into the Trial

• Histologically or cytologically confirmed non-small cell lung cancer, performed on a biopsy that occurred within the last 60 days.
• Positron Emission Tomography (PET)-CT within the last 30 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required).
• Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery-certified surgeon.
• Measurable disease as defined by RECIST v1.1.
• Adequate tissue specimens for correlative biomarker analysis. The patient should be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Principal Investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE Version 4.0 grade 1.

Inclusion Criteria

• Be willing and able to provide written informed consent/assent for the trial.
• Be at least 18 years of age on day of signing informed consent.
• Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of treatment initiation.

System Laboratory Value Hematological Absolute neutrophil count (ANC) greater than or equal to 1,500 /microliter (mcL) Platelets greater than or equal to 100,000 / mcL Hemoglobin greater than or equal to 9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)

Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) less than or equal to 1.5 X upper limit of normal (ULN) OR

Greater than or equal to 60 mL/min for subject with creatinine levels greater than 1.5 X institutional ULN Hepatic Serum total bilirubin Less than or equal to 1.5 X ULN aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) Less than or equal to 2.5 X ULN

Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)

Activated Partial Thromboplastin Time (aPTT) Less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Creatinine clearance should be calculated per institutional standard.

• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria

• Is ineligible for an operation based on medical or oncologic contraindications to surgery.
• Has history of non-infectious pneumonitis/interstitial lung disease that req