Nivolumab for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers

Exclusion Criteria

• •An individual who meets any of the following criteria will be excluded from participation in this study:
• •1. Participants may not be currently receiving immune checkpoint inhibitor treatment or have been treated with immune checkpoint inhibitors in the past (including anti-programmed cell death receptor \[PD\]-1, anti-programmed death ligand 1 \[PD-L1\], and anti-cytotoxic T-lymphocyte associated protein 4 \[CTLA4\] monoclonal antibodies)
• •2. Patients cannot receive any other investigational anti-cancer agents while participating in the study
• •3. Participants cannot have used any other investigational agents within the previous six months
• •4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
• •5. Clinically apparent bleeding diathesis (i.e., bleeding that is spontaneous, excessive, or delayed in onset following tissue injury results from a localized pathologic process or a disorder of the hemostatic process, involving a complex interplay among vascular integrity, platelet number and function, coagulation factors, and fibrinolysis)
• •6. Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or rare (\< 2 minute) premature ventricular contractions are not exclusionary
• •7. History of coronary artery disease, including myocardial infarction, congestive heart failure (LV ejection fraction \<50% or clinically significant diastolic dysfunction), or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the study
• •8. Individuals who are HIV-positive will be considered on a case-by-case basis, but will be required to meet criteria related to patient safety and data integrity, as assessed by the study investigators
• •9. History of hepatitis B or hepatitis C infection that is untreated and/or with a detectable viral load
• •10. Hypoxemia (less than 90% saturation with supplemental oxygen)
• •11. Severe obstructive lung disease (GOLD Stage III or IV, FEV1\<30% predicted)
• •12. Prior chemotherapy or thoracic radiation within the past 1 year
• •13. Participants with findings on CT chest suspicious for lung cancer (Lung-RADS category 4) will not be allowed to enroll until they have undergone additional evaluation for malignancy and an alternative (i.e., non-malignant) diagnosis has been established
• •14. Current malignancy, with the exception of non-melanoma (i.e., basal cell or squamous cell) skin cancer. Patients with lung carcinoma in situ found during the study biopsy are also excluded.
• •15. History of a malignancy except for adequately treated non-melanoma (i.e., basal cell or squamous cell) skin cancer or in situ cervical cancer for which the subject has not been disease-free for 5 years. Patients with a history of non-small cell lung cancer (stage I, II, or IIIA) or head and neck cancer (stage I, II, III, or IVA) must have no evidence of active disease at least 1 year after definitive treatment.
• •16. History of stage IIIA NSCLC for which the only treatment was chemoradiation without surgery
• •17. Known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism requiring hormone replacement, or skin disorders not requiring systemic treatment are permitted to enroll
• •18. Conditions requiring systemic corticosteroids equivalent to \> 10 mg prednisone per day or other immunosuppressive medications within 2 weeks of enrollment
• •19. Known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• •20. History of interstitial pneumonitis requiring treatment with systemic corticosteroids or other immunosuppressive agents (e.g., mycophenolate, azathioprine)
• •21. Life expectancy of \< 1 year
• •22. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 4 weeks prior to the start of nivolumab
• •23. Women must not be breastfeeding
• •24. Inability to give informed consent
• •25. Pneumonia or acute bronchitis for at least 2 weeks prior to enrollment