Canakinumab for Lung Cancer Risk Reduction in Former-Smokers
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Peter Shields
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.
Is the drug Canakinumab a promising treatment for reducing lung cancer risk in former smokers?The information provided does not directly address Canakinumab's effectiveness for reducing lung cancer risk in former smokers. The articles focus on immune checkpoint inhibitors and other treatments for lung cancer, but do not mention Canakinumab. Therefore, we cannot determine if Canakinumab is a promising treatment based on this information.2371012
What safety data is available for Canakinumab in lung cancer treatment?The provided research does not contain safety data specifically for Canakinumab (Ilaris, ACZ-885, ACZ885) in lung cancer treatment. The studies focus on immune checkpoint inhibitors, which are different from Canakinumab. For safety data on Canakinumab, other sources or studies specifically evaluating Canakinumab would need to be consulted.1591112
What data supports the idea that Canakinumab for Lung Cancer Risk Reduction in Former-Smokers is an effective drug?The available research shows that immune checkpoint inhibitors (ICIs) have been effective in improving outcomes for lung cancer patients, particularly those with non-small cell lung cancer (NSCLC). These drugs have been shown to improve survival rates when used alone or in combination with chemotherapy. However, there is no specific data provided about Canakinumab's effectiveness for lung cancer risk reduction in former smokers. The research focuses on other ICIs, which have been successful in treating lung cancer, but does not mention Canakinumab directly.346813
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications, but certain medications are prohibited. You cannot take daily NSAIDs, immunosuppressants, or certain immune-modulating agents during the study. If you are on medications like warfarin, your dose may need adjustment. Check with the trial team for specific guidance on your medications.
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 quit smoking more than 5 years ago.
Exclusion Criteria
I am taking more than 15 mg of methotrexate weekly.
I do not have any life-threatening diseases like cancer or severe liver, kidney, or immune system disorders.
I have not taken antibiotics in the last 30 days.
I am not taking any medications that are not allowed in the study.
I am currently taking immunosuppressants.
I am not currently taking any medication that affects my immune system.
I have been taking more than 20 mg of prednisone (or equivalent) daily for over 14 days.
I have been taking a steroid medication daily for more than 30 days.
I have not received any live vaccines in the last 90 days and won't during the study.
I haven't had any lung procedures in the last 6 months.
Treatment Details
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.
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
Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors. [2019]Checkpoint inhibitor pneumonitis (CIP) is an immune-related adverse event that can occur after initiation of anti-programmed death 1/programmed death ligand 1 immune checkpoint inhibitor (ICI) therapy for the treatment of multiple malignancies, including NSCLC. However, the incidence of CIP has not been previously examined in a population that included both trial-enrolled and non-trial-enrolled patients with advanced NSCLC. Furthermore, risk factors and other clinical characteristics associated with CIP severity are not known. In this study, we retrospectively examined clinical characteristics, incidence, and risk factors for CIP in a cohort of 205 patients with NSCLC, all of whom received anti-programmed death 1/programmed death ligand 1 ICIs. Our results demonstrate a higher incidence of CIP (19%) than previously reported in clinical trials (3%-5%). Our data also suggest that tumor histologic type may be a risk factor for CIP development. We observed a wide range of time to onset of CIP (median 82 days), with high morbidity and mortality associated with higher-grade CIP regardless of degree of immunosuppression. Our data provide new insight into the epidemiology and clinical characteristics of CIP. Further studies are needed to increase CIP pharmacovigilance, improve risk stratification, and refine diagnostic algorithms for the diagnosis and management of this potential life-threatening complication of ICI therapy.
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.
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.
First-line immune checkpoint inhibitors for advanced non-small cell lung cancer with wild-type epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK): a systematic review and network meta-analysis. [2022]To assess the comparative efficacy and safety of first-line immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK).
The incidence and relative risk of PD-1/PD-L1 inhibitors-related colitis in non-small cell lung cancer: A meta-analysis of randomized controlled trials. [2020]The programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors have shown encouraging merits in non-small cell lung cancer (NSCLC) patients, however, they are often related to potentially fatal immune-related adverse events (irAEs) including colitis. Considering the incidence and characteristics of immune-related colitis may have significant implications for the appropriate utilization of PD-1/PD-L1 inhibitors in clinical practice, we conduct this meta to systematically analyze the correlation between PD-1/PD-L1 inhibitors for the treatment of NSCLC and the incidence of immune-associated colitis.
Restricted mean survival time in advanced non-small cell lung cancer treated with immune checkpoint inhibitors. [2022]The purpose of this study was to review the effectiveness of immune checkpoint inhibitors (ICIs) in the first-line treatment of advanced non-small cell lung carcinoma with wild-type epidermal grow factor receptor (EGFR) or anaplastic lymphoma kinase.
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).
Immunotherapy in Lung Cancer: Are the Promises of Long-Term Benefit Finally Met? [2022]Over the last few years, agents targeting immune checkpoints have shown potential to improve therapeutic outcomes in patients with lung cancer in multiple clinical settings. Inhibitors of PD-1/PD-L1 have been approved for the treatment of different types of lung cancer by the FDA either alone or in combination with chemotherapy or other immune checkpoint inhibitors, such as anti-CTLA-4 agents. The introduction of these agents in clinical practice has revolutionized the therapeutic approach to lung cancer, keeping the promises of long-term benefit in selected patient populations. The therapeutic indications of immunotherapy in lung cancer are rapidly growing, and multiple combinations entered clinical practice or are under active development. Furthermore, the quest for a reliable predictive biomarker is still ongoing to overcome the limits of currently approved tests for patients' selection. In this review, we summarized the current status and progress of anti-PD-1/PD-L1 agents in lung cancer treatment.
Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis. [2022]We aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature.
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.
Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. [2022]With the increased use of immune checkpoint inhibitors (ICIs) in advanced lung cancer, adverse events (AEs), particularly immune-related AEs (irAEs), have garnered considerable interest. We conducted a comprehensive assessment of the toxicity profile in advanced lung cancer using multi-source medical data.
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.
The landscape of immune therapy in vulnerable patients with advanced non-small cell lung cancer: a narrative review. [2023]The clinical development of immune checkpoint inhibitors (ICIs) has led to substantial advances in the treatment of lung cancer. In particular, the contribution of ICIs to the long-term survival of certain patients with non-small cell lung cancer (NSCLC) has been reported. With the accumulated experience in the use of ICIs, numerous studies have documented the efficacy and safety of ICIs in patients with diverse backgrounds, including those with problematic indications for drug therapy. In the current review, we summarize the most recent literature-based findings on ICI administration in vulnerable patients with NSCLC and provide an overview of the current status and prospects of ICIs.