Nivolumab for Lung Cancer Prevention in Smokers

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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Nivolumab for lung cancer prevention in smokers?

Nivolumab has shown promise in treating advanced non-small-cell lung cancer (NSCLC) by improving overall survival and progression-free survival in patients, as seen in several studies. It works by enhancing the immune system's ability to fight cancer, and has been found to be more effective than some traditional chemotherapy drugs like docetaxel. ^{1 2 3 4 5}

Is Nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been shown to have a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and melanoma, although it can be associated with immune-related side effects. When combined with another drug, ipilimumab, the risk of side effects may increase, but it is generally considered safe for use in humans. ^{3 6 7 8 9}

How is the drug Nivolumab unique for lung cancer prevention in smokers?

Nivolumab is unique because it is an immune checkpoint inhibitor that enhances the body's immune response against cancer cells by blocking the PD-1 pathway, which is different from traditional chemotherapy that directly targets cancer cells. This approach can potentially lead to longer-lasting effects and fewer side effects compared to conventional treatments. ^{1 5 10 11 12}

Research Team

Robert Keith, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

I have never been treated with immune checkpoint inhibitors.

Timeline

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Does nivolumab for progressed metastatic lung cancer fulfill its promises? An efficacy and safety analysis in 20 general hospitals. [2021]

3. England 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. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarker. [2022]

5. United States 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. [2019]

6. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

7. United States 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. [2023]

8. Germany 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. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Nivolumab monotherapy or combination therapy with ipilimumab for lung cancer: a systemic review and meta-analysis. [2021]

11. Hungary pubmed.ncbi.nlm.nih.gov

[Immunotherapy for lung cancer]. [2019]

12. England 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. [2022]