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

Status: Active


This phase II trial studies how well nivolumab works in preventing lung cancer in participants who are high risk current and former smokers with or without a history of lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Eligibility Criteria

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 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.

Locations & Contacts


Rocky Mountain Regional VA Medical Center
Status: Active
Contact: Robert Leonard Keith
Phone: 720-857-5120
University of Colorado Hospital
Status: Active
Contact: Robert Leonard Keith
Phone: 720-857-5120

Trial Objectives and Outline


I. To determine whether immune checkpoint blockade using nivolumab can reverse premalignant histological changes in the bronchial epithelium of subjects at high risk for developing lung cancer as defined by bronchial dysplasia; and either 30 pack-years of tobacco exposure with sputum cytologic atypia, or history of early-stage lung or head and neck cancer at least 1 year after definitive treatment.


I. To assess the safety and tolerability of nivolumab in patients with bronchial dysplastic lesions.


I. To identify novel prognostic and predictive markers present at the time of diagnosis.


Participants receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants undergo a bronchoscopy at 8 weeks and 6 months.

After completion of study treatment, participants are followed up annually for 5 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
University of Colorado Hospital

Principal Investigator
Robert Leonard Keith

Trial IDs

Primary ID 17-1492
Secondary IDs NCI-2018-01723 ID NCT03347838