Canakinumab for Lung Cancer Prevention

Overseen By Jianjun Zhang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-IL1beta, Immunotherapy

Disqualifiers: Active infection, Psychiatric disorders, 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: 11

Duration: 24 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if canakinumab, a monoclonal antibody, can prevent lung cancer in individuals with high-risk lung nodules. Canakinumab may help by blocking the growth and spread of cancer cells. It suits individuals with certain lung nodules identified on CT scans that remain unchanged over time, particularly those who have received treatment for early-stage lung cancer and show no clear signs of cancer from a biopsy. This trial may be worth considering for those in this situation. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain cancer treatments or investigational drugs other than canakinumab. It's best to discuss your specific medications with the trial team.

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

Research shows that canakinumab is generally safe for people with high-risk lung nodules. Studies have found that most people tolerate it well, and it may help prevent lung cancer. Some side effects, mainly infections and injection site reactions, have been reported, but these align with known effects of canakinumab. Overall, current research suggests that canakinumab is safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lung cancer, such as chemotherapy and radiation, Canakinumab is unique because it targets inflammation by inhibiting a specific protein called interleukin-1 beta (IL-1β). This approach is different from typical cancer therapies that directly attack cancer cells. By reducing inflammation, Canakinumab may help prevent cancer development in high-risk individuals. Researchers are excited about this treatment because it represents a novel way to potentially stop lung cancer before it starts, offering a preventative strategy rather than just a treatment for existing cancer.

What evidence suggests that canakinumab might be an effective treatment for preventing lung cancer?

Research has shown that canakinumab might help prevent lung cancer. In the CANTOS trial, canakinumab significantly reduced lung cancer cases and deaths, with about a 70% drop in cases among those who received the treatment. Canakinumab targets a specific inflammation pathway, believed to be involved in cancer growth and spread. Although some studies did not show improved outcomes for certain lung cancer types, the decrease in cases from the CANTOS trial suggests promise, especially for high-risk individuals. Participants in this trial will receive canakinumab as part of the prevention strategy. ^{1 2 3 6 7}

Who Is on the Research Team?

Jianjun Zhang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-risk lung nodules who may develop lung cancer. They must have certain blood and organ function levels, agree to use contraception, and not be pregnant or breastfeeding. Those with active cancers, recent live vaccines, or psychiatric/substance issues can't join.

Inclusion Criteria

I agree to use birth control and not donate sperm during the study.

My kidney function is stable without needing blood transfusions or erythropoietin in the last 2 weeks.

Your bilirubin levels in your blood need to be within a certain range.

Exclusion Criteria

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have another cancer that is getting worse or was treated in the last year.

I am currently taking specific medications as part of this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive canakinumab subcutaneously on day 1, with treatment repeating every 21 days for up to 8 cycles

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab

Trial Overview The Can-Prevent-Lung Trial is testing if the drug Canakinumab can prevent lung cancer in patients with risky pulmonary nodules. It's a phase II study where participants receive this monoclonal antibody that might stop tumor growth.

How Is the Trial Designed?

Group I: Prevention (canakinumab) Experimental Treatment 2 Interventions

Patients receive canakinumab SC on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a phase III study involving 643 patients with advanced non-small-cell lung cancer, the addition of canakinumab to standard treatment did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to placebo.

Despite the lack of survival benefit, canakinumab was found to delay the deterioration of lung cancer symptoms, indicating potential quality of life improvements for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab Versus Placebo in Combination With First-Line Pembrolizumab Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Results From the CANOPY-1 Trial. Tan, DSW., Felip, E., de Castro, G., et al.[2023]

Canakinumab, an IL-1β inhibitory antibody, shows potential in reducing lung cancer incidence based on previous trials, prompting further investigation into its mechanism in lung cancer treatment.

In co-cultures of lung cancer cells and macrophages, IL-1β levels were significantly higher compared to monocultures, suggesting that interactions between these cells may enhance IL-1β expression and activate the NF-κB pathway, highlighting its role as a potential therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the NF-κB Pathway Agonist IL-1β on Non-Small Cell Lung Cancer Cell Lines. Liu, D., Liu, XQ., Kiefl, R., et al.[2021]

Canakinumab, an anti-IL-1β antibody, has shown promise in reducing lung cancer incidence, suggesting that targeting inflammation in the tumor microenvironment can enhance cancer treatment outcomes.

The CANOPY program is investigating the combination of canakinumab with PD-1 inhibition as a potential chemotherapy-free immunotherapy strategy, particularly for patients with non-small-cell lung cancer who typically have low PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming immunosuppression and pro-tumor inflammation in lung cancer with combined IL-1β and PD-1 inhibition. Lee, JM., Tsuboi, M., Kim, ES., et al.[2022]

Canakinumab is an effective treatment for inflammatory diseases like familial cold auto-inflammatory syndrome and Muckle-Wells syndrome, as it neutralizes IL-1beta signaling to reduce inflammation.

The drug is generally well-tolerated with no serious adverse effects reported, and it offers benefits such as bimonthly administration and approval for use in children, making it a promising option for various autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab. Dhimolea, E.[2021]

The CANOPY-N trial is a Phase II study designed to evaluate the effectiveness of canakinumab, an IL-1β inhibitor, in treating non-small-cell lung cancer, potentially reducing lung cancer incidence based on previous findings from the CANTOS trial.

Patients with stage IB to IIIA non-small-cell lung cancer will receive either canakinumab or pembrolizumab, alone or in combination, with the primary goal of assessing major pathological response, which will help determine the treatment's efficacy before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab with and without pembrolizumab in patients with resectable non-small-cell lung cancer: CANOPY-N study design. Garrido, P., Pujol, JL., Kim, ES., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04789681

Canakinumab for the Prevention of Lung Cancer, the Can- ... This phase II trial studies the effects of canakinumab in preventing lung cancer in patients who have high-risk pulmonary nodules.

2. novartis.com novartis.com/news/media-releases/novartis-provides-update-phase-iii-canopy-study-evaluating-canakinumab-adjuvant-treatment-non-small-cell-lung-cancer

Novartis provides update on Phase III CANOPY-A study ... Phase III CANOPY-A trial did not meet primary endpoint of disease-free survival in patients with stages II-IIIA and IIIB completely resected ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33023946/

An Exploratory Analysis of the CANTOS Trial Inhibition of the IL1β inflammatory pathway by canakinumab has been shown to significantly reduce lung cancer incidence and mortality.

4. nature.com nature.com/articles/s41416-022-01893-5

Repositioning canakinumab for non-small cell lung cancer ... On October 25, 2021, Novartis announced the anti-interleukin-1β (IL-1β) drug, canakinumab in non-small cell lung cancer (NSCLC) did not improve ...

5. jto.org jto.org/article/S1556-0864(23)00936-X/fulltext

MA03.10 The Interim Analysis of Can-Prevent-Lung Trial Canakinumab, a humanized anti-ILB antibody has been demonstrated to decrease lung cancer incidence by ∼70% in CANTOS trial. This single arm Phase II trial aims ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12075943/

Post-marketing safety of anakinra and canakinumab: a real ... At the PT level, both anakinra and canakinumab exhibited significant signals of AEs related to infections and ISRs. These AEs generally aligned ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1556086424011225

P1.01A.03 Can-Prevent-Lung Trial-Canakinumab for the ... Conclusions. Canakinumab has exhibited a favorable safety profile and promising efficacy in the treatment of patients with high-risk lung nodules. Methylation ...