“These findings further strengthen the evidence that IL1RAP plays a critical role in pancreatic cancer and is associated with the most aggressive forms of the disease,” said David Liberg, CSO of Cantargia. “Importantly, these compelling data show that IL1RAP can be effectively targeted to fundamentally alter the tumor microenvironment, resulting in both direct inhibition of tumor growth and improved responsiveness to therapies that would otherwise have limited or no effect. We believe these findings further support the potential of nadunolimab as a novel treatment patients with pancreatic cancer.”

The data demonstrates potent effects of a mouse surrogate antibody of nadunolimab in a preclinical model of aggressive KRAS-mutated PDAC. Treatment with the surrogate antibody strongly inhibited tumor growth in this difficult-to-treat model and led to distinct changes in the tumor microenvironment. This effect primed the tumor for response to chemoimmunotherapy, which is otherwise ineffective in this model.

Analyses of human PDAC samples showed that IL1RAP expression is elevated in the tumor microenvironment and selectively enriched in tumors from treatment-resistant patients. Furthermore, in tumor specimens from patients enrolled in the CANFOUR trial and treated with nadunolimab in combination with gemcitabine and nab-paclitaxel, high IL1RAP expression in stromal and immune cells was associated with prolonged duration of response.

Together, these findings suggest that IL1RAP expression in the pancreatic tumor represents a distinct therapeutic barrier that contributes to treatment resistance in PDAC. Targeting these cells with nadunolimab may help improve sensitivity to both chemotherapy and immunotherapy.

The data produced are relevant for both early and late-stage PDAC. Recent clinical data point to RAS-inhibition as a future backbone for treatment of second-line metastatic PDAC and Cantargia is preparing for a clinical study in this patient population in combination with a RAS-inhibitor. Dr Jashodeep Datta and collaborators at the Sylvester Comprehensive Cancer Center are also preparing for an IIT in the neoadjuvant setting, investigating the combination of nadunolimab with chemoimmunotherapy patients with operable PDAC.

“Our findings identify IL1RAP-expressing myeloid and stromal cell networks as dominant drivers of treatment resistance in pancreatic cancer,” said Dr. Jashodeep Datta, Associate Professor of Surgery and DiMare Family Chair in Immunotherapy at the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine. “By targeting these networks, we observed profound changes in the tumor microenvironment that enhanced responsiveness to chemoimmunotherapy in preclinical models. These results highlight IL1RAP as both a promising therapeutic target and a potential biomarker for patient response. We look forward to collaborating with Cantargia also on clinical development, including a neoadjuvant trial here at Sylvester Comprehensive Cancer Center.”

The article entitled “IL1RAP-expressing myeloid-stromal networks represent a therapeutic vulnerability to improve chemoimmunotherapy sensitivity in pancreatic cancer” by Dickey, Marsh et al., is available via the JCI Insight website and at Cantargias website.

The publication is based in part on results previously presented at scientific conferences during 2025 and 2026.