Nivolumab for Lung Cancer Prevention in Smokers

Not currently recruiting at 1 trial location

Overseen By Brandi Kubala

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Immune checkpoint inhibitors, Corticosteroids

Disqualifiers: Bleeding diathesis, Cardiac dysrhythmia, Coronary artery disease, Severe lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nivolumab, a medication that aids the immune system in fighting cancer, can improve lung conditions in individuals at high risk for lung cancer. The focus is on those with lung changes that could lead to cancer, particularly those with a history of heavy smoking or previous lung or head and neck cancer. The study will also evaluate the safety and tolerability of nivolumab for these individuals. Current or former heavy smokers with specific lung health issues might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immune checkpoint inhibitors or investigational anti-cancer agents while participating.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that nivolumab is already used to treat some types of lung cancer. Prospective trial participants should understand its safety profile. Studies involving individuals with non-small cell lung cancer, a common type, have found that nivolumab is usually well-tolerated. However, serious side effects, such as pneumonia (a lung infection) and breathing problems, occurred in about 2% of patients. While not very common, these side effects remain possible.

Nivolumab has also been linked to pneumonitis (lung inflammation). This side effect was more common in patients with a history of lung issues (31%) compared to those without (12%). Therefore, individuals with previous lung problems might face a higher risk.

Since the FDA has already approved nivolumab for other conditions, extensive safety information is available. While side effects can occur, they are known and monitored. Prospective participants should discuss any concerns with the trial team to understand how these findings might relate to their situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer prevention?

Most treatments for lung cancer focus on attacking cancer cells directly or stopping their growth. However, nivolumab, also known as Opdivo, works differently by enhancing the body’s immune system to recognize and fight cancer cells. Researchers are excited about nivolumab because it blocks a protein called PD-1, which can help cancer cells hide from the immune system. By targeting this pathway, nivolumab helps the immune system detect and destroy cancer cells more effectively. This approach could offer a new way to prevent lung cancer in smokers, potentially improving outcomes where traditional treatments might fall short.

What evidence suggests that nivolumab might be an effective treatment for lung cancer prevention in smokers?

Research has shown that nivolumab, a type of medication, effectively treats non-small cell lung cancer (NSCLC). Studies found that 18% of patients with advanced NSCLC responded positively to the treatment, and 45% survived for at least one year. This trial will investigate whether nivolumab might prevent lung cancer from worsening, especially in high-risk individuals like smokers or those with a history of lung cancer. Importantly, smoking status does not seem to affect nivolumab's effectiveness, which is encouraging for smokers considering this trial. Overall, these findings strongly support its potential to help with early lung conditions that could lead to cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Robert Keith, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

You have significant abnormal changes in your airways found during a special lung exam.

Your total granulocyte count is higher than 1500.

Your blood platelet count is higher than 100,000.

Exclusion Criteria

I do not have a condition that causes unusual bleeding.

Women must not be breastfeeding

You have had allergic reactions to drugs that are similar to nivolumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab 240 mg IV every two weeks for a total of four doses

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bronchoscopy with endobronchial biopsy at 2 months and 6 months

6 months

2 visits (in-person)

Long-term follow-up

Participants are monitored for immune-related adverse events every 3 months through 1 year

1 year

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Nivolumab Injection [Opdivo] Experimental Treatment 1 Intervention

240 mg IV every 2 weeks for 4 doses

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a phase III trial, nivolumab significantly improved health-related quality of life (HRQoL) and disease-related symptoms compared to docetaxel in patients with advanced non-squamous non-small cell lung cancer, with improvements noted at multiple time points (weeks 12, 24, 30, and 42).

Patients receiving nivolumab experienced a longer time to first deterioration in HRQoL compared to those treated with docetaxel, indicating a more favorable safety profile and sustained symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Reck, M., Brahmer, J., Bennett, B., et al.[2019]

Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell lung cancer, based on a meta-analysis of 20 studies involving 3404 patients.

The presence of PD-L1 expression in patients is associated with a better response to nivolumab, indicating that PD-L1 status can help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. Zhao, B., Zhang, W., Yu, D., et al.[2019]

Citations

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Effect of smoking status on immunotherapy for lung cancer Our findings suggest that smoking status does not affect the effectiveness of immunotherapy for lung cancer treatment.

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Tobacco smoking and cessation and PD-L1 inhibitors in ... Programmed death ligand 1 (PD-L1) targeting immunotherapies, as pembrolizumab and nivolumab, have significantly improved outcome in patients with non-small ...

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Nivolumab for Lung Cancer Prevention in Smokers Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell ...

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Efficacy Data for Non-Small Cell Lung Cancer (NSCLC) - Opdivo Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or ...

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Safety Profile for Non-Small Cell Lung Cancer (NSCLC) The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract ...

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Real-world safety of nivolumab in patients with non-small ... All NSCLC patients treated with nivolumab between 17 December 2015 and 31 March 2016 were registered and monitored for one year. Safety data were accumulated ...

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PO-412 Effectiveness and safety of anti-PD1 (Nivolumab ... Anti-PD1 therapy (Nivolumab) has shown tumoral activity in the treatment of advanced NSCLC pts. Nivolumab is a fully human IgG4 PD-1 immune-checkpoint ...

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Clinical trial results for stage 1B, 2, or 3A early-stage non- ... An FDA-approved combination of immunotherapy and chemotherapy that helped reduce the risk of cancer spreading or returning compared to platinum-based ...