Canakinumab for Lung Cancer Risk Reduction in Former-Smokers

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Peter Shields

Must not be taking: NSAIDs, Steroids, Immunosuppressants, others

Disqualifiers: Smoking, Obesity, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 11 weeks

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as daily aspirin, NSAIDs, immunosuppressants, and some steroids, before and during the study. If you are on medications that affect the immune system, you may need to stop them for at least 130 days after the study. It's best to discuss your specific medications with the study team.

How is the drug Canakinumab unique for reducing lung cancer risk in former smokers?

Canakinumab is unique because it is an anti-inflammatory drug that targets a specific protein called interleukin-1 beta (IL-1β), which is different from traditional lung cancer treatments like chemotherapy or immune checkpoint inhibitors that focus on attacking cancer cells directly. This approach may help reduce inflammation-related cancer risk in former smokers. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial tests the impact of canakinumab on biologic samples (buccal, nasal, and blood) from former smokers with increased risk of cancer. Canakinumab blocks the activity of a protein called interleukin-1 beta (IL-1b), an agent of the inflammatory system and is used for the treatment of different non-cancer diseases (like auto-inflammatory diseases). Giving canakinumab may block the inflammatory system and could have positive effects to reduce cancer growth.

Research Team

Peter G. Shields, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for former smokers aged 55-73 with a history of heavy smoking (30+ pack-years) and high inflammation markers (hsCRP >= 2 mg/L). Participants must not have smoked or used tobacco/vaping products in the last five years. Women should be post-menopausal, on contraception, or sterilized. People with unstable medical conditions, recent serious infections like COVID-19, or those taking certain medications are excluded.

Inclusion Criteria

I am between 55 and 73 years old.

I am a male sterilized at least 6 months ago, or my only partner is a vasectomized male.

I am post-menopausal or have a negative pregnancy test.

Exclusion Criteria

I am taking more than 15 mg of methotrexate weekly.

I am currently taking immunosuppressants.

I have not had COVID-19 or its symptoms in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive canakinumab subcutaneously and undergo bronchoscopy and sample collection

11 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in immune cell composition and inflammatory markers

4 weeks

Treatment Details

Interventions

• Canakinumab

Trial Overview The trial is testing canakinumab's effects on reducing cancer growth risk by examining its impact on inflammatory biomarkers in biologic samples from high-risk former smokers. Canakinumab targets interleukin-1 beta to potentially disrupt cancer-promoting inflammation.

Participant Groups

Group I: Prevention (canakinumab, bronchoscopy) Experimental Treatment 5 Interventions

Patients undergo bronchoscopy over 30-60 minutes and receive canakinumab SC 60 minutes and 2 weeks after the initial bronchoscopy. Patients undergo an additional bronchoscopy on day 77. Patients undergo buccal, nasal, and blood sample collection and CO testing on study.

Canakinumab is already approved in European Union, United States for the following indications:

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

Peter Shields

Lead Sponsor

Trials

1

Recruited

80+

Findings from Research

Patients with a history of tobacco use may experience greater benefits from immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC), with hazard ratios indicating improved outcomes compared to never smokers.

Ex-smokers show a more significant response to ICI therapy than current smokers, suggesting that smoking history could be an important factor in treatment decision-making for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer. Corke, LK., Li, JJN., Leighl, NB., et al.[2022]

Immune-checkpoint inhibitors (ICIs), especially those targeting the PD-1 axis, have significantly improved survival rates in non-small cell lung cancer (NSCLC) patients, particularly in those with high PD-L1 expression when used as first-line therapy.

Recent studies show that combining ICIs with chemotherapy enhances survival for NSCLC patients regardless of PD-L1 levels, although identifying the best candidates for ICI treatment remains complex due to the variability of biomarkers like PD-L1 and tumor mutational burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes. Doroshow, DB., Sanmamed, MF., Hastings, K., et al.[2023]

In a systematic review of 2,484 patients with advanced ALK-positive non-small cell lung cancer (NSCLC), smoking status did not significantly affect treatment efficacy overall, but specific analyses showed that smokers in the Asian population had better progression-free survival (PFS) with ALK inhibitors compared to never-smokers.

Among treatment options, lorlatinib was the most effective for never-smokers, while low-dose alectinib showed superior efficacy in smokers, suggesting tailored treatment strategies based on smoking status may be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis. Lin, K., Lin, J., Huang, Z., et al.[2022]

In a study of 189 patients with oncogene-driven non-small cell lung cancer (NSCLC), smoking status was identified as a significant predictor of response to PD-1/PD-L1 inhibitors, with smokers showing a 16.9% objective response rate compared to 0% in never-smokers.

The presence of KRAS mutations and PD-L1 positivity also influenced treatment outcomes, with smokers having better progression-free survival rates, highlighting the importance of these factors in predicting the efficacy of immunotherapy in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive value of oncogenic driver subtype, programmed death-1 ligand (PD-L1) score, and smoking status on the efficacy of PD-1/PD-L1 inhibitors in patients with oncogene-driven non-small cell lung cancer. Ng, TL., Liu, Y., Dimou, A., et al.[2019]

In a meta-analysis of 23 randomized clinical trials and 7 real-world studies involving 10,643 patients with non-small cell lung cancer (NSCLC), immunotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in smokers compared to chemotherapy, with hazard ratios of 0.76 and 0.65, respectively.

Smokers receiving immunotherapy also showed prolonged OS and PFS compared to non-smokers, indicating that patients with a smoking history may benefit more from immunotherapy in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Zhao, W., Jiang, W., Wang, H., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Smoking on Response to the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Predictive value of oncogenic driver subtype, programmed death-1 ligand (PD-L1) score, and smoking status on the efficacy of PD-1/PD-L1 inhibitors in patients with oncogene-driven non-small cell lung cancer. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2022]