Nivolumab in Preventing Lung Cancer in High Risk Current and Former Smokers with or without a History of Lung Cancer

Inclusion Criteria

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• A current or ex-smoker with a >= 30 pack-year history of smoking and mild or worse sputum cytologic atypia or known bronchial dysplasia, OR history of non-small cell lung cancer (stage I, II, or IIIA) with >= 10 pack-year history of smoking and no evidence of active disease at least 1 year after definitive treatment, OR history of head and neck cancer (stage I, II, III, or IVA) with >= 10 pack-year history of smoking and no evidence of active disease at least 1 year after definitive treatment. An ex-smoker is defined as no tobacco use in the prior 12 months.
• Endobronchial dysplasia (score >= 4) on screening bronchoscopy.
• Total granulocyte count > 1500.
• Platelet count > 100,000.
• Serum creatinine =< 1.5 mg/dL.
• Total bilirubin =< 2.0 mg/dL.
• Transaminases and alkaline phosphatase =< 2.5x upper limit of normal (ULN).
• Albumin >= 2.5 mg/dL.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1.
• Participants must be able and willing to undergo three bronchoscopies: before, after four doses of nivolumab (8 weeks), and after 6 months.

Exclusion Criteria

• 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).
• Patients cannot receive any other investigational anti-cancer agents while participating in the study.
• Participants cannot have used any other investigational agents within the previous six months.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• 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).
• 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.
• History of coronary artery disease, including myocardial infarction, congestive heart failure (left ventricle [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.
• Individuals who are human immunodeficiency virus (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.
• History of hepatitis B or hepatitis C infection that is untreated and/or with a detectable viral load.
• Hypoxemia (less than 90% saturation with supplemental oxygen).
• Severe obstructive lung disease (Global Initiative for Obstructive Lung Disease [GOLD] Stage III or IV, forced expiratory volume in one second [FEV1] < 30% predicted).
• Prior chemotherapy or thoracic radiation within the past 1 year.
• Participants with findings on computed tomography (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.
• 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.
• 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.
• History of stage IIIA non-small cell lung cancer (NSCLC) for which the only treatment was chemoradiation without surgery.
• 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.
• Conditions requiring systemic corticosteroids equivalent to > 10 mg prednisone per day or other immunosuppressive medications within 2 weeks of enrollment.
• Known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• History of interstitial pneumonitis requiring treatment with systemic corticosteroids or other immunosuppressive agents (e.g., mycophenolate, azathioprine).
• Life expectancy of < 1 year.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 4 weeks prior to the start of nivolumab.
• Women must not be breastfeeding.
• Inability to give informed consent.
• Pneumonia or acute bronchitis for at least 2 weeks prior to enrollment.