Canakinumab for Lung Cancer Risk Reduction in Former-Smokers
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Peter Shields
Must not be taking: NSAIDs, Steroids, Immunosuppressants, others
Disqualifiers: Smoking, Obesity, Lung disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
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.
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.12345
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.
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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.
See 25 more
Trial 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 (Monoclonal Antibodies)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Prevention (canakinumab, bronchoscopy)Experimental Treatment5 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who Is Running the Clinical Trial?
Peter ShieldsLead Sponsor
References
Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer. [2022]Tobacco is a known risk factor for lung cancer, and continued tobacco use is associated with poorer outcomes across multiple lung cancer treatment modalities including surgery, chemotherapy and radiation therapy. Less is known about the association of tobacco use and outcomes with immune checkpoint inhibitors (ICIs), which are becoming an important part of the treatment landscape in lung cancer, both in metastatic and curative settings. We reviewed the literature on the association of tobacco and tumor biology as it relates to immunotherapy. We also reviewed the association of tobacco use on outcomes among phase III randomized clinical trials involving ICIs in non-small cell lung cancer (NSCLC). We identified that patients with a smoking history may have a greater benefit with ICI treatment compared to never smokers in both treatment-naïve (HR 0.82, 95% CI 0.69-0.97, vs. HR 1.06, 95% CI 0.81-1.38) and pre-treated (HR 0.79, 95% CI 0.70-0.90 vs. 1.03, 95% CI 0.74-1.43) settings. In trials where smoking status was further defined, ex-smokers appear to demonstrate greater benefit with ICI therapy compared to current smokers (HR 0.78, 95% CI 0.59-1.01 vs. 0.91, 95% CI 0.72-1.14). We conclude by offering our perspective on future directions in this area of research, including implementation of standardized collection and analysis of tobacco use in clinical trials involving ICI therapy in lung cancer and other disease sites, and also evaluating how tobacco may affect toxicities related to ICI therapy. Based on our review, we believe that a patient's history of tobacco smoking does have a role to play in guiding treatment decision making in patients with lung cancer.
Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes. [2023]Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non-small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.
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]Background: The impact of smoking on the efficacy of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treatment is controversial and has not been systematically explored in the first-line setting. We performed a systematic review based on a pairwise meta-analysis and a Bayesian network meta-analysis (NMA) to address this issue. Methods: PubMed, Embase, Web of Science, Cochrane Library, Clinical-Trials.gov, and other resources were searched until 5 January 2022. Progression-free survival (PFS) was considered the main outcome of interest. Randomized controlled trials with smoking status analysis were included. Cochrane Risk of Bias Tool was performed to assess the risk of bias. Random effects models were adopted conservatively in meta-analysis. The NMA was performed in a Bayesian framework using the "gemtc" version 1.0-1 package of R-4.1.2 software. Results: A total of 2,484 patients from nine studies were eligible for this study, with 1,547 never-smokers (62.3%) and 937 smokers (37.7%). In a pairwise meta-analysis, in the overall population, no significant difference was found between never-smokers and smokers. However, in the subgroup analyses based on crizotinib-controlled studies, anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) derived better PFS in the smoking group over the never-smoking group in the Asian population (HR = 0.17, 95%CI = 0.09-0.31 in the smoking group, HR = 0.39, 95%CI = 0.24-0.65 in the never-smoking group, p = 0.04, low quality of evidence). In NMA, among never-smokers, lorlatinib ranked the highest for PFS (SUCRA = 96.2%), but no significant superiority was found among the new-generation ALK-TKIs except for ceritinib. In smokers, low-dose alectinib performed best (SUCRA = 95.5%) and also demonstrated a significant superiority over ensartinib (HR = 0.23, 95%CI = 0.08-0.68, very low quality of evidence), brigatinib (HR = 0.38, 95%CI = 0.14-0.99, low quality of evidence), ceritinib (HR = 0.24, 95%CI = 0.09-0.66, low quality of evidence), crizotinib (HR = 0.18, 95%CI = 0.08-0.41, moderate quality of evidence), and chemotherapy (HR = 0.11, 95%CI = 0.05-0.28, low quality of evidence). Conclusion: In general, smoking may not affect the treatment efficacy of advanced ALK-positive NSCLC in the first-line setting. However, alectinib may perform better in the smoking Asian population. Moreover, lorlatinib in never-smokers and low-dose alectinib in smokers could be considered optimal first-line therapy for advanced ALK-positive NSCLC. Acceptable limitations of evidence, such as study risk of bias, inconsistency, and imprecision, were present in this NMA.
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]This multicenter, retrospective study explored the value of oncogene driver subtype, programmed death-1 ligand (PD-L1) status, and smoking status for predicting which patients with oncogene-driven non-small cell lung cancer (NSCLC) would benefit from treatment with programmed death-1 (PD-1)/PD-L1 inhibitors.
Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2022]To evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).