WCLC 2025 - Posters & ePosters-P2.02.36 Canakinumab Interception Trial and Preclinical Studies Reveal Stage-Dependent Biology in Lung Cancer and Precancers

P2.02.36 Canakinumab Interception Trial and Preclinical Studies Reveal Stage-Dependent Biology in Lung Cancer and Precancers

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This study investigates the stage-dependent biology of lung cancer and its precursors through the Can-Prevent-Lung trial, a phase II clinical trial evaluating canakinumab, an interleukin-1β (IL-1β) antibody. While prior clinical trials with canakinumab in established lung cancers had negative results, earlier research indicated innate immunity and IL-1β play critical roles in lung adenocarcinoma (LUAD) precursor evolution. The hypothesis is that IL-1β inhibition is more effective in intercepting precancerous lesions than treating invasive lung cancers.<br /><br />The trial focused on patients with persistent high-risk lung nodules—nodules present over at least two CT scans spaced three months apart without shrinkage and classified based on Brock University Criteria. Canakinumab treatment showed potential efficacy by enhancing regression rates of these nodules, supported by radiographic shrinkage, reduced lesion volumes, and clearance of tumor DNA detected via whole genome sequencing. Additionally, blood cytokine levels (e.g., ICOSL, IL-8, MIG) increased post-treatment, indicating immune activation.<br /><br />Preclinical mouse models demonstrated that early-stage IL-1β blockade significantly inhibited lesion progression, reducing adenoma and hyperplasia areas, whereas late-stage treatment lacked efficacy and did not improve survival. Single-cell RNA sequencing revealed that anti-IL-1β treatment activated T and B cells at early stages but not at late stages, consistent with increased macrophage antigen presentation and T cell activation signatures only early on. Spatial transcriptomics confirmed immune cell changes in lung tissue following early IL-1β blockade.<br /><br />Overall, the findings indicate lung cancer biology and therapeutic response are stage-dependent. Early interception via IL-1β inhibition can modulate innate immunity, activating adaptive immune responses to prevent progression from precancerous nodules to invasive lung cancer. The study supports further investigation of canakinumab as a lung cancer interception strategy and highlights radiomics plus molecular/immune blood profiling as valuable tools in this setting.

Asset Subtitle

Jianjun Zhang

Meta Tag

Speaker Jianjun Zhang

Topic Tumor Biology – Preclinical Biology

Keywords

lung cancer

canakinumab

interleukin-1β

IL-1β inhibition

lung adenocarcinoma

precancerous nodules

immune activation

early-stage intervention

radiomics

molecular blood profiling