Bronchial DysplasiaPhase 2NCT03347838
Nivolumab for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers
A Phase 2 study testing Nivolumab in people with Bronchial Dysplasia and Tobacco Smoking, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
The goal of this clinical research study is to determine whether the PD-1 inhibitor (Programmed cell death protein 1) nivolumab improves premalignant bronchial dysplastic lesions in subjects that are at high risk for the development of lung cancer, including those with a prior smoking history, or history of lung… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Bronchial Dysplasia, Tobacco Smoking, History of Non-Small Cell Lung Cancer
- What is being tested?
- Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jan 2019to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following 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
- Male or female, aged > 18 years
- 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
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- 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
- Albumin > 2.5 mg/dL
- 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
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- 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)
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- 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 (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 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 (GOLD Stage III or IV, FEV1<30% predicted)
- Prior chemotherapy or thoracic radiation within the past 1 year
- 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
- 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 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 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Denver VA Hospital
Denver, Colorado, 80220
About this study
Official title: PD-1 Immune Checkpoint Inhibition for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers With or Without a History of Lung Cancer
The goal of this clinical research study is to determine whether the PD-1 inhibitor (Programmed cell death protein 1) nivolumab improves premalignant bronchial dysplastic lesions in subjects that are at high risk for the development of lung cancer, including those with a prior smoking history, or history of lung cancer or head and neck cancer. The safety and tolerability of nivolumab will also be studied.
Read the detailed description
This is a single-institution, open-label, single-arm, two-stage, phase II study of the PD-1 inhibitor nivolumab in patients at high risk for lung cancer. Simon's two-stage design will be used. In the first stage, 18 subjects will be enrolled. If at least 7 subjects respond to nivolumab, then an additional 24 subjects will be enrolled for a total of 42 subjects. The central hypothesis to be tested by this trial is that immune evasion contributes to malignant transformation of premalignant bronchial dysplastic lesions into invasive lung cancers, and that blocking PD-1 will allow the immune system to target and eradicate premalignant bronchial dysplastic lesions, thereby preventing the development of lung cancer.
Nivolumab 240 mg IV will be administered every two weeks for a total of four doses (8 weeks). Participants will undergo bronchoscopy with endobronchial biopsy at study entry, 2 months, and 6 months. The primary endpoint will be change in bronchial dysplasia between study entry and the 6 month timepoint. Secondary endpoints include safety and tolerability of nivolumab in patients with bronchial dysplastic lesions, and additional endobronchial histology endpoints. Exploratory endpoints will be used to identify predictive markers of response to nivolumab.
- Conditions
- Bronchial Dysplasia, Tobacco Smoking, History of Non-Small Cell Lung Cancer, History of Head and Neck Cancer
- Being tested
- Nivolumab
- Keywords
- PD-1, Precancerous Conditions, Nivolumab, Lung Cancer Immunoprevention
- Medical subject headings
- Tobacco Smoking, Head and Neck Neoplasms, Precancerous Conditions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo, BMS-936558, MDX1106, ONO-4538
Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab Injection [Opdivo] | Experimental | 240 mg IV every 2 weeks for 4 doses Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Endobronchial Histology
The primary endpoint is the dichotomous endpoint of whether a subject responds to PD-1 immune checkpoint inhibition using nivolumab. Response will be based on the 6-month change (difference between 6-month score and baseline score) in worst (i.e., maximum) histologic classification score, using the 2004 World Health Organization (WHO) classification scale for pre-invasive squamous lesions of the bronchus. The histologic classification consists of: normal (grade 1.0), reserve cell hyperplasia (grade 2.0), squamous metaplasia (grade 3.0), mild dysplasia (grade 4.0), moderate dysplasia (grade 5.0), severe dysplasia (grade 6.0), carcinoma in situ (grade 7.0) and invasive cancer (grade 8.0).
Measured: 6 months
Secondary outcomes (2)
Incidence of Immune-related Adverse Events (irAEs)
Patients will be evaluated every 2 weeks to determine whether they have any immune-related adverse events (irAEs) using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). In particular, patients will be monitored closely for evidence of dermatological, gastrointestinal, endocrine, renal, and pulmonary irAEs. Complete blood count, comprehensive metabolic profile, and thyroid function tests will be obtained at baseline and every 3 months for 1 year. A comprehensive metabolic profile will also be checked every 2 weeks. Subjects will be followed for a total of 1 year to monitor for development of irAEs after discontinuation of the study drug.
Measured: Every 2 weeks through 3 months, then every 3 months through 1 year
Additional Endobronchial Histology Endpoints Using the 2004 WHO Classification Scale for Pre-invasive Squamous Lesions of the Bronchus
- Two-month change (difference between 2-month score and baseline score) in worst (i.e., maximum) histologic classification score
- Using all dysplastic (i.e., histology score ≥ 4.0) baseline biopsy pairs, the change in average histology and dysplasia index
- Using all matched biopsies, the change in worst histology, average histology, and dysplasia index
- Using all matched biopsies from reference sites, the change in worst histology, average histology, and dysplasia index
- Response to treatment of completers, based on worst histology
Measured: 2 months and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2017
- Study start30 Jan 2019
- Primary completion18 Jun 2025
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bronchial DysplasiaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The goal of this clinical research study is to determine whether the Programmed cell death protein 1 (PD-1) inhibitor nivolumab improves premalignant bronchial dysplastic lesions in subjects that are at high risk for the development of lung cancer, including those with a prior smoking history, or history of lung cancer or head and neck cancer. The safety and tolerability of nivolumab will also be studied.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Robert Keith, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03347838
- Sponsor's protocol ID
- 17-1492.cc
- Status last verified
- Dec 2025
- First submitted
- 24 Oct 2017
- Last updated
- 12 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PD-1 Immune Checkpoint Inhibition for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers With or Without a History of Lung Cancer
- ClinicalTrials.gov ID
- NCT03347838
- Acronym / sponsor ID
- 17-1492.cc
- Conditions
- Bronchial Dysplasia, Tobacco Smoking, History of Non-Small Cell Lung Cancer, History of Head and Neck Cancer
- Keywords
- PD-1, Precancerous Conditions, Nivolumab, Lung Cancer Immunoprevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 30 Jan 2019 (actual)
- Primary completion
- 18 Jun 2025 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 20 Nov 2017 (actual)
- Results
- Posted 12 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to determine whether the PD-1 inhibitor (Programmed cell death protein 1) nivolumab improves premalignant bronchial dysplastic lesions in subjects that are at high risk for the development of lung cancer, including those with a prior smoking history, or history of lung cancer or head and neck cancer. The safety and tolerability of nivolumab will also be studied.
Detailed description
This is a single-institution, open-label, single-arm, two-stage, phase II study of the PD-1 inhibitor nivolumab in patients at high risk for lung cancer. Simon's two-stage design will be used. In the first stage, 18 subjects will be enrolled. If at least 7 subjects respond to nivolumab, then an additional 24 subjects will be enrolled for a total of 42 subjects. The central hypothesis to be tested by this trial is that immune evasion contributes to malignant transformation of premalignant bronchial dysplastic lesions into invasive lung cancers, and that blocking PD-1 will allow the immune system to target and eradicate premalignant bronchial dysplastic lesions, thereby preventing the development of lung cancer.
Nivolumab 240 mg IV will be administered every two weeks for a total of four doses (8 weeks). Participants will undergo bronchoscopy with endobronchial biopsy at study entry, 2 months, and 6 months. The primary endpoint will be change in bronchial dysplasia between study entry and the 6 month timepoint. Secondary endpoints include safety and tolerability of nivolumab in patients with bronchial dysplastic lesions, and additional endobronchial histology endpoints. Exploratory endpoints will be used to identify predictive markers of response to nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The goal of this clinical research study is to determine whether the Programmed cell death protein 1 (PD-1) inhibitor nivolumab improves premalignant bronchial dysplastic lesions in subjects that are at high risk for the development of lung cancer, including those with a prior smoking history, or history of lung cancer or head and neck cancer. The safety and tolerability of nivolumab will also be studied.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab Injection [Opdivo] | Experimental | Drug: Nivolumab240 mg IV every 2 weeks for 4 doses |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following 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
- Male or female, aged > 18 years
- 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
Key exclusion criteria (26 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: Opdivo, BMS-936558, MDX1106, ONO-4538Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. | Drug | Nivolumab Injection [Opdivo] |
Primary outcome
Improvement in Endobronchial Histology
Time frame: 6 months
The primary endpoint is the dichotomous endpoint of whether a subject responds to PD-1 immune checkpoint inhibition using nivolumab. Response will be based on the 6-month change (difference between 6-month score and baseline score) in worst (i.e., maximum) histologic classification score, using the 2004 World Health Organization (WHO) classification scale for pre-invasive squamous lesions of the bronchus. The histologic classification consists of: normal (grade 1.0), reserve cell hyperplasia (grade 2.0), squamous metaplasia (grade 3.0), mild dysplasia (grade 4.0), moderate dysplasia (grade 5.0), severe dysplasia (grade 6.0), carcinoma in situ (grade 7.0) and invasive cancer (grade 8.0).
2 secondary outcomes
Incidence of Immune-related Adverse Events (irAEs)
Time frame: Every 2 weeks through 3 months, then every 3 months through 1 year
Additional Endobronchial Histology Endpoints Using the 2004 WHO Classification Scale for Pre-invasive Squamous Lesions of the Bronchus
Time frame: 2 months and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Bronchial Dysplasia
RecruitingObservational study
Biomarkers in Patients With Respiratory Tract Dysplasia or Lung Cancer, Head and Neck Cancer, or Aerodigestive Tract Cancer and in Normal Volunteers
Esophageal Cancer, Head and Neck Cancer
Not yet recruiting
PremaBiom: Metatranscriptomics of the Respiratory Microbiome to Predict the Occurrence of Bronchopulmonary Dysplasia in Preterm Infants
Bronchopulmonary Dysplasia, Preterm Infant Development
Not yet recruitingPhase 3
Enhancing Lung Health in Kids With Structural Lung Damage and Malformations: Azithromycin (AZI) for Airway Infection Prevention
Tracheomalacia, Bronchopulmonary Dysplasia (BPD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Keith, MD principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab in people with Bronchial Dysplasia and Tobacco Smoking, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Endobronchial Histology (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.