What side effects are associated with this type of intervention?

PD-1 inhibitors, such as nivolumab, are being studied for the treatment of bronchial dysplasia. Common side effects of PD-1 inhibitors include fatigue, rash, diarrhea, and pruritus. More severe adverse effects can include immune-related reactions such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. These immune-related adverse events require careful monitoring and management.

What prior FDA approvals exist?

There are no specific FDA approvals for the treatment of bronchial dysplasia. However, nivolumab, a PD-1 inhibitor, is being studied for its potential in improving premalignant bronchial dysplastic lesions. Similar immunotherapy drugs, such as pembrolizumab and atezolizumab, have been approved for various types of non-small cell lung cancer (NSCLC), indicating a broader acceptance of PD-1 and PD-L1 inhibitors in treating lung-related conditions.

What other types of research exist?

Promising alternatives to Nivolumab for bronchial dysplasia patients include Pembrolizumab and Atezolizumab, both of which are PD-1/PD-L1 inhibitors. Additionally, emerging therapies such as Cemiplimab and Durvalumab, which target similar pathways, may also be considered.

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PD-1 Inhibitor

Nivolumab for Lung Cancer Prevention in Smokers

Phase 2

Waitlist Available

Led By Robert Keith, MD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG performance status ≤ 1 (Appendix 1)

Participants must be able and willing to undergo three bronchoscopies: before, after four doses of nivolumab (8 weeks), and after 6 months

Must not have

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)

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)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 2 weeks through 3 months, then every 3 months through 1 year

Awards & highlights

Summary

This trial tests if nivolumab can help prevent lung cancer in high-risk individuals by enabling their immune system to attack pre-cancerous cells. The study will also check if nivolumab is safe and well-tolerated.

Who is the study for?

This trial is for adults over 18 who have a history of heavy smoking or past non-small cell lung cancer/head and neck cancer with no active disease for at least a year. They must be able to undergo multiple bronchoscopies, not currently on immune checkpoint inhibitors, without severe heart issues, bleeding disorders, untreated hepatitis B/C, other cancers within the last 5 years (except certain skin/cervical cancers), or life-threatening arrhythmias.

What is being tested?

The study tests if Nivolumab can improve premalignant bronchial lesions in high-risk individuals due to smoking or previous lung/head and neck cancers. It also assesses the drug's safety. Participants will receive Nivolumab and undergo evaluations including bronchoscopies before treatment, after four doses (8 weeks), and after six months.

What are the potential side effects?

Nivolumab may cause immune-related side effects such as inflammation in organs like lungs or intestines, skin reactions, hormone gland problems (like thyroid dysfunction), liver issues, kidney problems including nephritis and renal failure; infusion reactions; fatigue; weakness.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active and can carry on all my pre-disease activities without restriction.

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I am willing to undergo three bronchoscopies as part of the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have a condition that causes unusual bleeding.

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I have never been treated with immune checkpoint inhibitors.

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I have untreated hepatitis B or C with a detectable viral load.

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I have severe lung disease with very low lung function.

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I haven't taken high doses of steroids or other immune-weakening drugs in the last 2 weeks.

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I am unable to understand and agree to the study's details.

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I have been treated for lung inflammation with strong medications.

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I have lung disease that could affect my treatment.

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I had stage IIIA lung cancer treated only with chemoradiation, no surgery.

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My CT scan shows possible lung cancer, but I've been cleared of cancer after further tests.

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I have not had chemotherapy or chest radiation in the last year.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every 2 weeks through 3 months, then every 3 months through 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every 2 weeks through 3 months, then every 3 months through 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and every 2 weeks through 3 months, then every 3 months through 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Improvement in endobronchial histology

Secondary study objectives

Additional endobronchial histology endpoints using the 2004 WHO classification scale for pre-invasive squamous lesions of the bronchus

Incidence of immune-related adverse events (irAEs)

Other study objectives

Number of non-synonymous mutations in bronchial dysplastic lesions

Proportion of T lymphocytes in bronchial dysplastic lesions that express PD-1

Proportion of macrophages in bronchial dysplastic lesions that express PD-L1

+2 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Cushingoid

10%

Tinnitus

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Trial Design

1Treatment groups

Experimental Treatment

Group I: Nivolumab Injection [Opdivo]Experimental Treatment1 Intervention

240 mg IV every 2 weeks for 4 doses

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Nivolumab is a PD-1 inhibitor that works by blocking the programmed death-1 (PD-1) pathway, which cancer cells often exploit to evade the immune system. By inhibiting this pathway, Nivolumab enhances the body's immune response against abnormal cells, including premalignant bronchial dysplastic lesions. This is particularly important for patients with bronchial dysplasia, as it can potentially prevent the progression to invasive lung cancer by allowing the immune system to target and eliminate dysplastic cells more effectively.

[Chemotherapy of non-small cell bronchial cancers. Meta-analysis of the literature as a function of the extent of the disease].Small cell carcinoma of the lung.Algorithm for the treatment of advanced or metastatic squamous non-small-cell lung cancer: an evidence-based overview.