Ilaris (canakinumab)

P=N/A, N=160, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2027 --> Dec 2026 | Trial primary completion date: Mar 2027 --> Dec 2026

Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations...Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

P=N/A, N=160, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Sep 2026 --> Mar 2027 | Trial primary completion date: Sep 2026 --> Mar 2027

P=N/A, N=5, Not yet recruiting, Novartis Pharmaceuticals

Given the limited antitumor efficacy of IL-1β-targeting agents such as Anakinra and Canakinumab, we focused on IRAK4 as a therapeutic target. RNA-seq revealed enrichment of neutrophil activation signatures and suppression of extracellular matrix (ECM) gene programs. Together, these findings establish a role for the IL-1β/IL1R1/IRAK4 axis in inflammation-driven PSM and peritoneal seeding and ECM regulation in EOC, and demonstrate that IRAK4 inhibition activates antitumor immune responses, providing a therapeutic strategy to block metastatic seeding and improve tumor control.

Therapeutically, IL-1α blockers using agents such as anakinra, canakinumab, and nadunolimab show synergy with immune checkpoint inhibitors and chemotherapy. This includes the recruitment of neutrophils and myeloid-derived suppressor cells (MDSCs), which collectively maintain an immunosuppressive ('cold') tumor microenvironment (TME) and contribute to therapeutic resistance. Future multi-omics stratification, targeted delivery systems, and rational combination strategies hold promise for improving PDAC outcomes.

These findings underscore significant safety signals associated with canakinumab, including infections, gastrointestinal/hepatobiliary disorders in children, and neoplasms in older patients. The dual temporal pattern of AEs underscores the need for both short- and long-term surveillance.

P1, N=17, Completed, Columbia University | Active, not recruiting --> Completed

P2, N=120, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

P=N/A, N=160, Not yet recruiting, Novartis Pharmaceuticals

P=N/A, N=5000, Recruiting, Duke University | Trial primary completion date: Sep 2026 --> Mar 2027

P1, N=9, Active, not recruiting, NYU Langone Health | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jul 2026