Overcoming immunosuppression and pro-tumor inflammation in lung cancer with combined IL-1β and PD-1 inhibition

Inflammation in the tumor microenvironment is a complicit and known carcinogenesis driver. Inhibition of IL-1β, one of the most abundant and influential cytokines in the tumor microenvironment, may enhance the efficacy of PD-1. In a post-hoc analysis of phase III cardiovascular CANTOS trial, canakinumab, a monoclonal anti-IL-1β antibody, significantly reduced lung cancer incidence. Immune checkpoint inhibition (ICI) is the standard of care in non-small-cell lung cancer. However, ICI efficacy is heavily impacted by programmed death ligand-1 (PD-L1) status. Most patients with non-small-cell lung cancer have low PD-L1 expression levels. Thus, combinational strategies are needed to improve ICI efficacy and expand its use. Here, we describe the preclinical and clinical evidence to support the combination of IL-1β and PD-1 under investigation in the CANOPY program. The perioperative use of canakinumab with or without PD-1 inhibition in the CANOPY-N trial is described as a potential chemotherapy-free immunotherapy strategy.IL-1β is a small molecule involved in the spreading of cancer cells and scouting for cells that work against the body’s protective inflammatory response. In a follow-up analysis of the CANTOS study, people with atherosclerosis who received canakinumab, a drug which limits the activity of IL-1β in the body, were diagnosed with lung cancer less often than people who received an inactive substance. Immunotherapy is a treatment that can boost the natural defenses of the immune system, but how well it works varies from patient to patient. Recent efforts aim to understand whether blocking unhealthy inflammation with canakinumab and stimulating the body’s protective system with immunotherapy at the same time could be an efficacious treatment for patients with lung cancer. Currently there are limited data from experiments in cell and animal models; however, data from the ongoing CANOPY-N clinical trial, which is investigating this treatment combination prior to surgery for patients with lung cancer, are expected by the first half of this year.