Trial Outcomes & Findings for Nivolumab for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers (NCT NCT03347838)
NCT ID: NCT03347838
Last Updated: 2025-12-12
Results Overview
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).
ACTIVE_NOT_RECRUITING
PHASE2
19 participants
6 months
2025-12-12
Participant Flow
Participants for this trial were recruited from pulmonary, oncology and nodule clinics from the Rocky Mountain Regional Veterans Affairs Medical Center (RMR VAMC) and the University of Colorado Hospital (UCHealth). The recruitment period for this study was January 2019 through January 2023. The trial included a sputum cytology pre-screening arm to screen for mild or worse sputum atypia, and an option for direct enrollment to full-study with a history of bronchial dysplasia.
All participants who enrolled onto the full-study underwent a baseline bronchoscopy; if biopsy results showed either mild, moderate or severe bronchial dysplasia at least one biopsy site, participants were eligible to move forward to full-study registration. If all biopsy sites did not reveal at least mild dysplasia, or if at least one site showed persistent carcinoma in situ or invasive carcinoma, this rendered participants ineligible for full-study registration.
Participant milestones
| Measure |
Nivolumab Injection [Opdivo]
240 mg IV every 2 weeks for 4 doses
|
|---|---|
|
Overall Study
STARTED
|
19
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nivolumab for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers
Baseline characteristics by cohort
| Measure |
Nivolumab Injection [Opdivo]
n=19 Participants
240 mg IV every 2 weeks for 4 doses
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=26 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=26 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=26 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=26 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=26 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=26 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=26 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=26 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=26 Participants
|
PRIMARY outcome
Timeframe: 6 monthsThe 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).
Outcome measures
| Measure |
Nivolumab Injection [Opdivo]
n=19 Participants
240 mg IV every 2 weeks for 4 doses
|
|---|---|
|
Improvement in Endobronchial Histology
|
10 Participants
|
SECONDARY outcome
Timeframe: Every 2 weeks through 3 months, then every 3 months through 1 yearPatients 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 months and 6 months1. Two-month change (difference between 2-month score and baseline score) in worst (i.e., maximum) histologic classification score 2. Using all dysplastic (i.e., histology score ≥ 4.0) baseline biopsy pairs, the change in average histology and dysplasia index 3. Using all matched biopsies, the change in worst histology, average histology, and dysplasia index 4. Using all matched biopsies from reference sites, the change in worst histology, average histology, and dysplasia index 5. Response to treatment of completers, based on worst histology
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 2 months, and 6 monthsThe proportion of T lymphocytes that express programmed death receptor 1 (PD-1) in pre- and post-treatment biopsies will be compared by immunofluorescence staining of formalin-fixed, paraffin-embedded tissue sections
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 2 months, and 6 monthsThe proportion of macrophages that express programmed death ligand 1 (PD-L1) in pre- and post-treatment biopsies will be compared by immunofluorescence staining of formalin-fixed, paraffin-embedded tissue sections
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 2 months, and 6 monthsPre- and post-treatment biopsies will be stained by immunofluorescence for Th1, Th2, and Treg CD4+ T lymphocytes
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 2 months, and 6 monthsPre- and post-treatment biopsies will be stained by immunofluorescence for CD68, HLA-DRA, and CD206. The ratio of M1 (CD68/HLA-DRA) to M2 (CD68/CD206) macrophages will be determined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineThe number of non-synonymous mutations in bronchial dysplastic lesions will be determined by whole exome sequencing
Outcome measures
Outcome data not reported
Adverse Events
Nivolumab Injection [Opdivo]
Serious adverse events
| Measure |
Nivolumab Injection [Opdivo]
n=19 participants at risk
240 mg IV every 2 weeks for 4 doses
|
|---|---|
|
Gastrointestinal disorders
Colitis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Bronchial infection
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Hepatobiliary disorders
Cholecystitis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Investigations
Weight Loss
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Investigations
Weight Loss/Severe Protein Calorie Malnutrition
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Renal and urinary disorders
Acute Kidney Injury
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Encephalopathy
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Sepsis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous disorders - other
|
5.3%
1/19 • Number of events 1 • 6 years
|
Other adverse events
| Measure |
Nivolumab Injection [Opdivo]
n=19 participants at risk
240 mg IV every 2 weeks for 4 doses
|
|---|---|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Dyspepsia
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Dysphagia
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.8%
3/19 • Number of events 3 • 6 years
|
|
General disorders
Edema limbs
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Encephalopathy
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
General disorders
Fatigue
|
63.2%
12/19 • Number of events 12 • 6 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - other, specify; Early satiety
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Headache
|
47.4%
9/19 • Number of events 9 • 6 years
|
|
Endocrine disorders
Hyperthyroidism
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Endocrine disorders
Hypothyroidism
|
26.3%
5/19 • Number of events 5 • 6 years
|
|
Infections and infestations
Infections and infestations - other, specify; COVID-19+
|
26.3%
5/19 • Number of events 5 • 6 years
|
|
Psychiatric disorders
Insomnia
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Intracranial hemorrhage
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
21.1%
4/19 • Number of events 4 • 6 years
|
|
Gastrointestinal disorders
Nausea
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
General disorders
Non-cardiac chest pain
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Infections and infestations
Otitis externa
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Otitis media
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Pancreatitis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Renal and urinary disorders
Renal and urinary disorders - other, specify: Overactive bladder
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - other, specify: uteral muscle spasm
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - other, specify: COPD Excacerbation
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Shingles
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Sinusitis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - other, specify: skin patch
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnea
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Nervous system disorders
Tremor
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Upper respiratory infection
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Infections and infestations
Urinary tract infection
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Ear and labyrinth disorders
Vertigo
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Abdominal pain
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Investigations
Alanine aminotransferase increased
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.8%
3/19 • Number of events 3 • 6 years
|
|
Investigations
Aspartate aminotransferase increased
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Immune system disorders
Autoimmune disorder (thyroiditis)
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Eye disorders
Blurred vision
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Colitis
|
10.5%
2/19 • Number of events 2 • 6 years
|
|
Infections and infestations
Conjunctivitis
|
5.3%
1/19 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.8%
3/19 • Number of events 3 • 6 years
|
|
Gastrointestinal disorders
Diarrhea
|
36.8%
7/19 • Number of events 7 • 6 years
|
|
Gastrointestinal disorders
Dry mouth
|
10.5%
2/19 • Number of events 2 • 6 years
|
Additional Information
Robert Keith, MD
Rocky Mountain Regional VA Medical Center / University of Colorado School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place