Canakinumab for Non-Small Cell Lung Cancer: A Comprehensive Review of Five Clinical Trials

Table of Contents

• Key Points
• Background: Why Researchers Studied Canakinumab for Lung Cancer
• How the Research Was Conducted
• Quality Assessment of the Included Studies
• Study and Patient Characteristics
• Key Findings: Efficacy Outcomes
• Key Findings: Safety Outcomes
• Clinical Implications: What This Means for Patients
• Limitations: What the Study Could Not Prove
• Recommendations and Future Directions
• Frequently Asked Questions
• Source Information

Key Points

• Across five trials in adjuvant, first-line, second-line, and neoadjuvant settings, canakinumab did not significantly improve response rates, progression-free survival, overall survival, or major pathologic response.
• In the 643-participant CANOPY-1 first-line trial, median progression-free survival was 6.8 months in both the canakinumab and placebo groups.
• Side effect rates were similar between canakinumab and control groups, and the drug was generally well tolerated across the five trials.
• All five trials excluded patients with EGFR or ALK alterations, so the findings may not apply to people with those genetic changes.
• Canakinumab is not currently recommended as a standard treatment for non-small cell lung cancer; standard care remains checkpoint inhibitors, targeted therapies, and chemotherapy.

Background: Why Researchers Studied Canakinumab for Lung Cancer

Lung cancer remains the leading cause of cancer-related death worldwide. It accounts for an estimated 1.8 million deaths every year. Non-small cell lung cancer (NSCLC) makes up approximately 85% of all lung cancer cases. NSCLC is further divided into subtypes: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Each subtype has distinct molecular features, clinical behavior, and treatment options.

The past decade has brought major advances in treating advanced NSCLC. These advances include immune checkpoint inhibitors that target the PD-1/PD-L1 axis (proteins that cancer cells use to hide from the immune system). They also include molecularly targeted therapies against specific genetic changes. These genetic changes include EGFR mutations, ALK rearrangements, ROS1 fusions, BRAF V600E mutations, and KRAS G12C mutations.

Despite these innovations, the five-year survival rate for metastatic NSCLC remains below 10%. This low survival rate underscores the urgent need for new treatment strategies. Researchers are looking for approaches that target different mechanisms of tumor growth and immune escape.

Interleukin-1 beta (IL-1β) is a pro-inflammatory cytokine (a signaling protein that promotes inflammation). It has emerged as an important factor in the development and progression of lung cancer. IL-1β contributes to tumor growth and spread through several mechanisms, which makes it a potential therapeutic target.

One of its primary roles is promoting angiogenesis (the growth of new blood vessels that feed tumors). IL-1β induces the production of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. This helps cancer cells grow and survive. IL-1β also enhances tumor invasiveness by stimulating the secretion of matrix metalloproteinases. These are enzymes that degrade the extracellular matrix and allow cancer cells to invade surrounding tissues.

Beyond its direct effects on tumor cells, IL-1β shapes the tumor microenvironment. It recruits immunosuppressive cells such as myeloid-derived suppressor cells and tumor-associated macrophages. These cells suppress anti-tumor immune responses and create an environment that favors tumor progression.

IL-1β also activates the NF-κB pathway. This leads to the transcription of genes involved in cell survival, proliferation, and inflammation, further contributing to tumor growth. It also plays a role in inducing epithelial-to-mesenchymal transition, a process that changes the metastatic potential of cancer cells.

Recent studies have highlighted an interaction between IL-1β and immune checkpoints. This research suggests that IL-1β may upregulate the expression of programmed death-ligand 1 (PD-L1) on tumor cells. This upregulation contributes to immune evasion by inhibiting T-cell activity, enabling tumors to escape immune surveillance.

Canakinumab is a human monoclonal antibody that targets IL-1β. It belongs to a class of biologic therapies designed to modulate inflammatory pathways. Unlike anakinra, a recombinant IL-1 receptor antagonist that requires daily subcutaneous administration due to its short half-life, canakinumab has a longer half-life. This allows dosing every 3 weeks, which improves patient convenience and adherence. This difference in pharmacokinetics (how the body processes a drug) is important. Canakinumab's sustained inhibition of IL-1β suppresses inflammatory signaling more than the transient blockade provided by anakinra. Canakinumab's specificity for neutralizing IL-1β, rather than broadly targeting IL-1 receptors, may also reduce off-target effects and improve therapeutic precision.

In the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), a cardiovascular trial, exploratory analyses revealed a dose-dependent reduction in lung cancer incidence and mortality among participants receiving canakinumab. This finding suggested a potential anticancer effect mediated through IL-1β inhibition.

Despite growing interest in targeting IL-1β for lung cancer treatment, the therapeutic potential of canakinumab remains uncertain. Several clinical trials have explored its efficacy, but findings have been inconsistent. No significant survival benefit was observed in subsequent studies. The current study aims to systematically evaluate the efficacy and safety of targeting this pathway with canakinumab compared with other standard therapies. The goal is to better define its potential for improving clinical outcomes in NSCLC treatment.

How the Research Was Conducted

This systematic review followed PRISMA guidelines (a standardized framework for reporting systematic reviews). The researchers searched four electronic databases: PubMed, Scopus, Web of Science, and Embase. The search covered all records from the inception of each database to May 13, 2026.

The search query combined terms related to "Canakinumab" with terms related to "Lung cancer." No language restrictions were imposed during the electronic searches. Records in all languages were considered for screening, with translation performed as needed for potentially eligible non-English studies. No automated study-type or publication-type filters were applied. This preserved maximum sensitivity for all clinically relevant study designs.

In addition to searching the databases, the researchers screened the first 300 results from Google Scholar. They also performed backward and forward citation searching on the included studies to identify additional relevant articles.

Two authors independently screened the retrieved records' titles and abstracts to determine inclusion eligibility. Any disagreements were resolved through discussion and, if necessary, by consultation with a third author. The inclusion criteria were original clinical trial studies that evaluated canakinumab as an intervention in patients with NSCLC, regardless of histological subtype. No language restrictions were applied. Studies were excluded if they involved other IL-1 inhibitors, or were animal studies, conference abstracts, or review articles. After the initial screening, the full texts of potentially eligible studies were assessed to confirm their suitability.

Data extraction was conducted systematically by two independent authors. The following information was collected from each included study:

• First author and study title
• Year of publication and country
• Study design and phase of the trial
• Study population and demographics
• Smoking status
• Follow-up duration
• Intervention characteristics
• Lung cancer subtype and primary disease stage
• Survival metrics (overall survival, progression-free survival)
• Adverse events

The quality of the included studies was assessed using appropriate tools based on their study design. For randomized controlled trials (RCTs), the Cochrane Risk of Bias (RoB) 2 tool was used. This tool evaluates bias across five domains: the randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. Studies were categorized as having low, some concerns, or high risk of bias.

For non-randomized studies, the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) Version 2 tool was used. This tool evaluates non-randomized studies across seven domains, including confounding, participant selection, classification of interventions, deviations from intended interventions, missing data, outcome measurement, and reporting bias. Each study was classified as having a low, moderate, serious, or critical risk of bias.

The researchers did not perform a meta-analysis (a statistical method that combines results from multiple studies). This was because of substantial clinical and methodological heterogeneity across the included trials. The trials differed in several major ways:

• Disease settings and stages: These spanned adjuvant therapy for completely resected early-stage disease (CANOPY-A), neoadjuvant therapy for resectable early-stage disease (CANOPY-N), first-line therapy for treatment-naïve advanced or metastatic disease (CANOPY-1 and Santoro et al.), and second-line therapy for pretreated advanced or metastatic disease (CANOPY-2).
• Treatment regimens: These ranged from canakinumab monotherapy to complex combinations with docetaxel, pembrolizumab, spartalizumab, or platinum-doublet chemotherapy.
• Control groups: These used placebo, active chemotherapy monotherapy, or immunotherapy alone.
• Study design: This ranged from a Phase Ib non-randomized trial to Phase III double-blind RCTs.
• Primary endpoints: These were mathematically non-combinable and included disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and major pathologic response (MPR).

The researchers noted that statistical pooling of these highly diverse settings and clinical endpoints would yield mathematically forced and clinically misleading summary estimates. Therefore, a narrative synthesis was conducted to systematically summarize the findings. The results were organized based on clinical settings. The researchers used the Synthesis Without Meta-analysis (SWiM) guidelines.

Quality Assessment of the Included Studies

The systematic literature search across four electronic databases yielded 2,005 records. These included 128 from PubMed, 1,465 from Scopus, 137 from Web of Science, and 275 from Embase. After removing 401 duplicate records, 1,604 records remained for screening based on their titles and abstracts. Of these, 1,595 records were excluded because they did not meet the inclusion criteria.

The remaining nine full-text articles were assessed for eligibility. Following a detailed evaluation, four articles were excluded. Three were conference abstracts, and one had insufficient data for efficacy and safety assessments. No further studies were found through Google Scholar. Ultimately, five studies met the criteria and were included in this systematic review.

For the four RCTs, the RoB 2 tool was used. All four RCTs demonstrated low risk of bias across all domains. For the one non-randomized study, the ROBINS-I Version 2 tool was used. There was a low risk of bias for all domains except domain 1, which is bias due to confounding. This domain was rated as moderate risk. Despite this single moderate risk rating, the overall quality assessment for the Santoro et al. study was determined to be low risk.

Study and Patient Characteristics

This systematic review included five multicenter studies: four RCTs and one open-label clinical trial. Three RCTs were phase III, one was phase II, and the open-label study was phase IB. The included studies were published between 2023 and 2025.

The sample sizes varied considerably across studies, ranging from 88 to 1,382 participants. The largest study was conducted by Garon et al. with 1,382 participants. This was followed by Tan et al. with 643 participants, Paz-Ares et al. with 237 participants, Santoro et al. with 111 participants, and Lee et al. with 88 participants.

All studies focused on patients with NSCLC but with different disease stages and prior treatment status. Here is a breakdown of each study's patient population:

• Paz-Ares et al. (CANOPY-2): Included stage IIIB/IV patients who had progressed after platinum-based chemotherapy and immunotherapy. The median age was 63 years (range 46–70) in the intervention group and 63 years (range 56–69) in the control group. The intervention group had 71% males, and the control group had 68% males.
• Garon et al. (CANOPY-A): Enrolled patients with completely resected stage II-IIIA/IIIB NSCLC after cisplatin therapy. The median age was 63 years (range 27–83) in the intervention group and 62 years (range 26–82) in the control group. The intervention group had 69% males, and the control group had 67% males.
• Tan et al. (CANOPY-1): Studied patients with advanced NSCLC and stable central nervous system (CNS) metastases. The median age was 63 years (range 57–69) in the intervention group and 64 years (range 56–69) in the control group. The intervention group had 72% males, and the control group had 70% males.
• Santoro et al.: Recruited treatment-naïve advanced NSCLC patients. The median age was 63 years (range 42–73) in the intervention group and 64 years (range 48–69) in the control group. The intervention group had 58% males, and the control group had 44% males.
• Lee et al. (CANOPY-N): Enrolled patients with resectable stage IB–IIIA NSCLC in the neoadjuvant setting. The median age was 67 years (range 61–75) in the intervention group and 67 years (range 61–75) in the control group. The intervention group had 59% males, and the control group had 58% males.

Treatment duration varied across studies. It ranged from 6 weeks (2 cycles) in Lee et al., to 14.8 weeks in Santoro et al., to 8.2 months in Tan et al., and approximately 12 months in Garon et al.

Follow-up periods were reported in three studies. These ranged from 33 weeks in Santoro et al., to 13.8 months in Paz-Ares et al., to 21.2 months in Tan et al. Garon et al. did not report follow-up duration, and Lee et al. focused on perioperative outcomes. All studies excluded patients with EGFR or ALK alterations.

Key Findings: Efficacy Outcomes

Across all clinical settings, canakinumab did not significantly improve objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or major pathologic response (MPR) compared with standard therapies. Here are the detailed results for each clinical setting.

First-line advanced/metastatic setting (CANOPY-1 and Santoro et al.):

The CANOPY-1 trial was the largest study included, with 643 participants. It evaluated canakinumab versus placebo in combination with first-line pembrolizumab plus platinum-based chemotherapy in patients with advanced NSCLC. The objective response rate was nearly identical between groups: 45.6% (95% CI: 40.1–51.3) in the canakinumab arm versus 45.5% (95% CI: 40.0–51.1) in the placebo arm. Median progression-free survival was 6.8 months in both groups, with a non-significant hazard ratio (HR) of 0.85 (95% CI: 0.67–1.09). Median overall survival was 20.8 months (95% CI: 16.3–NE) versus 20.2 months (95% CI: 16.2–22.4), with an HR of 0.87 (95% CI: 0.70–1.10). The disease control rate was 86.9% versus 84.8%, and median duration of response (DoR) was 14.3 versus 13.6 months.

The Santoro et al. phase Ib open-label trial compared spartalizumab plus pemetrexed/cisplatin with or without canakinumab in treatment-naïve advanced NSCLC. The objective response rate was 57.1% (95% CI: 18.4–90.1) in the canakinumab group versus 55.3% (95% CI: 38.3–71.4) in the control group. Median progression-free survival was 7.5 months (95% CI: 4.1–12.4) versus 10.4 months (95% CI: 5.4–26.4), favoring the control group. Median overall survival was 21.0 months (95% CI: 4.8–NE) versus 29.7 months (95% CI: 17.8–39.9), also favoring the control group. The disease control rate was 100% versus 81.6%, and median duration of response was 7.1 months versus 30.1 months. Neither study demonstrated a statistically significant benefit from the addition of canakinumab.

Second-line advanced/metastatic setting (CANOPY-2):

The CANOPY-2 trial, with 237 participants, evaluated canakinumab plus docetaxel versus placebo plus docetaxel in patients with stage IIIB/IV NSCLC who had progressed after prior platinum-based chemotherapy and immunotherapy. The objective response rate was 15% (95% CI: 9.1–22.7) in the canakinumab group versus 14% (95% CI: 8.0–21.3) in the placebo group. Median progression-free survival was 4.17 months (95% CI: 2.96–5.42) versus 4.21 months (95% CI: 3.06–5.13). Median overall survival was 10.55 months (95% CI: 8.15–12.39) versus 11.3 months (95% CI: 8.54–13.80), with an HR of 1.06 (95% CI: 0.76–1.48; one-sided p = 0.633). The disease control rate was 66% versus 62%, and median duration of response was 4.1 months (95% CI: 2.9–11.2) versus 5.4 months (95% CI: 4.2–NE). The study did not meet its primary endpoint of overall survival.

Adjuvant setting after complete resection (CANOPY-A):

The CANOPY-A trial, with 1,382 participants, evaluated canakinumab versus placebo as adjuvant therapy in patients with completely resected stage II-IIIA/IIIB NSCLC. The primary endpoint was disease-free survival (DFS). Median disease-free survival was 35.0 months in the canakinumab group versus 29.7 months in the placebo group (HR: 0.94; 95% CI: 0.78–1.14). This was a non-significant improvement. Objective response rate was not reported because of the adjuvant setting. No survival benefit was observed with canakinumab.

Neoadjuvant setting before surgery (CANOPY-N):

The CANOPY-N trial, with 88 participants, evaluated canakinumab alone, canakinumab plus pembrolizumab, or pembrolizumab alone as neoadjuvant therapy in patients with resectable stage IB–IIIA NSCLC. The primary endpoint was major pathologic response (MPR). MPR was achieved by 2.9% (95% CI: 0.07–14.92) of patients in the canakinumab monotherapy arm, 17.1% (95% CI: 6.56–33.65) in the canakinumab plus pembrolizumab arm, and 16.7% (95% CI: 3.58–41.42) in the pembrolizumab alone arm. This indicated no improvement with canakinumab-containing regimens. Per RECIST v1.1 criteria, no patient in the canakinumab arm achieved an objective response. Notably, 95.5% of patients successfully underwent surgery, with 85.7% achieving resection within the prespecified window. This demonstrated that canakinumab did not adversely affect surgical outcomes.

Key Findings: Safety Outcomes

Across the five studies reviewed, the overall incidence of treatment-related adverse events was high and comparable between the canakinumab (intervention) and control groups. Here are the detailed safety results from each study.

In the CANOPY-N trial, any-grade adverse events occurred in 88.6% of patients receiving canakinumab, 91.4% receiving the combination, and 83.3% receiving pembrolizumab. Grade 3/4 adverse events occurred in 28.6%, 25.7%, and 16.7%, respectively. Grade 5 adverse events occurred in 8.6% (canakinumab), 2.9% (combination), and 5.6% (pembrolizumab). All six on-treatment deaths occurred postoperatively, and none were treatment-related. No treatment-related grade 5 adverse events were reported in any arm.

Paz-Ares et al. reported any-grade adverse events in 88% of the intervention arm versus 85% of controls. Tan et al. observed 95.0% versus 93.8%. Garon et al. recorded 38.9% versus 31.5%. Santoro et al. noted 100% incidence in both groups.

For grade 3/4 adverse events, a trend for higher incidence in the intervention group was seen in Paz-Ares et al. (51% vs. 42%).

Clinical Implications: What This Means for Patients

The findings of this systematic review have important implications for patients with non-small cell lung cancer. Despite a strong scientific rationale for targeting IL-1β, canakinumab did not show significant clinical benefits in any of the clinical settings tested. This means that adding canakinumab to standard treatments did not improve response rates, delay cancer progression, or extend survival compared with standard treatments alone.

For patients considering canakinumab as part of their treatment plan, these results suggest that the drug is unlikely to provide meaningful benefit in the settings studied. However, the drug was generally well tolerated. Side effect rates were similar between canakinumab and control groups. However, the authors note that the risk of infection, particularly in heavily pretreated patients, warrants consideration.

The results also highlight the complexity of treating NSCLC. Even though IL-1β plays a clear role in tumor biology, blocking this pathway with canakinumab was not enough to improve outcomes. This suggests that lung cancer uses multiple pathways to grow and evade the immune system. Targeting a single pathway may not be sufficient.

Limitations: What the Study Could Not Prove

This systematic review has several limitations that patients and clinicians should consider. First, the researchers could not perform a meta-analysis because of substantial differences among the included trials. The trials differed in disease settings, treatment regimens, control groups, study designs, and primary endpoints. This means the findings are based on a narrative synthesis rather than a statistical combination of results.

Second, the sample sizes varied widely across studies, from 88 to 1,382 participants. Smaller studies may have less statistical power to detect meaningful differences. Third, follow-up durations differed across studies, and two studies did not report follow-up duration at all. This makes it difficult to compare long-term outcomes across trials.

Fourth, all studies excluded patients with EGFR or ALK alterations. This means the findings may not apply to patients with these specific genetic changes. Fifth, the review included only five studies, which limits the strength of the conclusions.

Finally, the review could not identify which patients, if any, might benefit from canakinumab. The researchers note that future research should concentrate on identifying predictive biomarkers. A predictive biomarker is a biological marker that can indicate which patients are likely to respond to a particular treatment.

Recommendations and Future Directions

Based on the findings of this systematic review, the authors make several recommendations for future research and clinical practice.

1. Identify predictive biomarkers: Future research should focus on finding biological markers that can predict which patients might benefit from canakinumab. This would allow for more targeted use of the drug.
2. Optimize combination strategies: Researchers should explore different ways to combine canakinumab with other treatments to enhance its therapeutic potential.
3. Consider patient selection: Since canakinumab did not benefit the overall patient populations studied, future trials should focus on specific subgroups that might respond better.
4. Continue safety monitoring: Although canakinumab was generally well tolerated, ongoing monitoring of side effects is important, especially in combination with other therapies.

For patients currently considering treatment options for NSCLC, the standard of care remains immune checkpoint inhibitors, molecularly targeted therapies, and chemotherapy, depending on the specific characteristics of the cancer. Canakinumab is not currently recommended as a standard treatment for NSCLC based on the evidence reviewed in this study.

Patients who are interested in clinical trials involving canakinumab or other novel therapies should discuss these options with their oncology team. Clinical trials remain an important option for patients with advanced NSCLC, especially when standard treatments are no longer effective.

Frequently Asked Questions

What is canakinumab and how does it work in lung cancer?

Canakinumab is a human monoclonal antibody that targets interleukin-1 beta, an inflammatory protein that can promote tumor blood vessel growth, invasion, and immune escape in lung cancer. It is given every three weeks. Researchers studied it in non-small cell lung cancer because earlier cardiovascular trial analyses suggested a possible anticancer effect, but its role remains uncertain.

Did canakinumab improve survival or response in the trials reviewed?

No. Across five trials covering adjuvant, first-line, second-line, and neoadjuvant settings, canakinumab did not significantly improve objective response rate, progression-free survival, overall survival, or major pathologic response compared with standard therapies. For example, in the 643-participant CANOPY-1 first-line trial, median progression-free survival was 6.8 months in both groups.

What side effects did patients taking canakinumab experience?

Side effect rates were similar between canakinumab and control groups, and the drug was generally well tolerated. In the CANOPY-N neoadjuvant trial, any-grade adverse events occurred in 88.6% of canakinumab patients versus 83.3% of pembrolizumab patients, and no treatment-related grade 5 events occurred in any arm. All six on-treatment deaths there were postoperative and not treatment-related.

Which patients were included in these canakinumab trials?

The five trials enrolled adults with non-small cell lung cancer at different stages and treatment points: after complete surgery, before surgery, and as first- or second-line therapy for advanced or metastatic disease. All studies excluded patients with EGFR or ALK alterations, so the findings may not apply to people with those specific genetic changes.

Can I get canakinumab as a standard treatment for NSCLC now?

Based on the evidence reviewed, canakinumab is not currently recommended as a standard treatment for non-small cell lung cancer. Standard care remains immune checkpoint inhibitors, molecularly targeted therapies, and chemotherapy, depending on the cancer's characteristics. If you are interested in canakinumab or other novel therapies, discuss clinical trial options with your oncology team.

What does it mean that the review could not identify who might benefit?

The review could not determine which patients, if any, might benefit from canakinumab. Researchers suggest future work should focus on predictive biomarkers, which are biological markers that may indicate who is likely to respond to a treatment. Until such markers are found, canakinumab's role in non-small cell lung cancer treatment remains uncertain.

Why didn't the researchers combine the trial results statistically?

They could not perform a meta-analysis because the five trials differed substantially in disease settings, treatment regimens, control groups, study designs, and primary endpoints. Combining such diverse results statistically would produce forced and clinically misleading estimates. Instead, they used a narrative synthesis, which is why the conclusions are based on a structured summary rather than a pooled number.

Can a second opinion change the treatment plan for non-small cell lung cancer when canakinumab is being considered?

Canakinumab did not significantly improve response rates, progression-free survival, overall survival, or major pathologic response in any setting tested, including first-line, second-line, adjuvant, and neoadjuvant therapy, and it is not currently recommended as a standard treatment for NSCLC. A second opinion can help confirm whether standard options such as immune checkpoint inhibitors, molecularly targeted therapies, or chemotherapy fit a patient's cancer characteristics, and whether a clinical trial is appropriate. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Efficacy and Safety of Canakinumab Compared With Standard Therapy for the Treatment of Non-Small Cell Lung Cancer (NSCLC): A Systematic Review.

Authors: Kamiar Izadpanah, Masoud Rezaei, Seyed Aria Nejadghaderi, Hamid Sharifi

Affiliations: HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran; Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran; Knowledge Hub for Migrant and Refugee Health, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran

Corresponding author: Seyed Aria Nejadghaderi

Journal: Cancer Reports, 2026; 9:e70627

Publication details: Received: 26 December 2025; Revised: 7 July 2026; Accepted: 11 July 2026

DOI: https://doi.org/10.1002/cnr2.70627

Keywords: canakinumab, carcinoma, Interleukin-1, non-small cell lung neoplasm, systematic review, treatment outcome

This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace consultation with a qualified healthcare provider. Patients should discuss their individual treatment options with their oncology team.