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

NCT03347838 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-1492.cc
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief 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 cancer or head and neck cancer. The safety and tolerability of nivolumab will also be studied.

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

Outcome Measures

Primary Outcomes (1)

• 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).

  6 months

Secondary Outcomes (2)

• Incidence of Immune-related Adverse Events (irAEs)

  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

  2 months and 6 months

Other Outcomes (5)

• Proportion of T Lymphocytes in Bronchial Dysplastic Lesions That Express PD-1

  Baseline, 2 months, and 6 months

• Proportion of Macrophages in Bronchial Dysplastic Lesions That Express PD-L1

  Baseline, 2 months, and 6 months

• Quantification of CD4+ T Lymphocyte Subsets in Bronchial Dysplastic Lesions

  Baseline, 2 months, and 6 months

Study Arms (1)

Nivolumab Injection [Opdivo]

EXPERIMENTAL

240 mg IV every 2 weeks for 4 doses

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Also known as: Opdivo, BMS-936558, MDX1106, ONO-4538

Nivolumab Injection [Opdivo]

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Denver VA Hospital

Denver, Colorado, 80220, United States

Location

MeSH Terms

Conditions

Tobacco Smoking; Head and Neck Neoplasms; Precancerous Conditions

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Smoking; Behavior; Tobacco Use; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Single-arm study.

Results Point of Contact

• Title: Robert Keith, MD
• Organization: Rocky Mountain Regional VA Medical Center / University of Colorado School of Medicine

robert.keith@cuanschutz.edu

720-857-5120

Study Officials

• Robert Keith, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: November 20, 2017
• Study Start: January 30, 2019
• Primary Completion: June 18, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 12, 2025
• Results First Posted: December 12, 2025

Record last verified: 2025-12

Locations

US (2)