Cantargia Highlights Preclinical Data at AACR Supporting Nadunolimab in Combination with RAS Inhibition in PDAC
Cantargia Highlights Preclinical Data at AACR Supporting Nadunolimab in Combination with RAS Inhibition in PDAC
Cantargia AB (publ) (Nasdaq Stockholm: CANTA) today announced the presentation of a poster on nadunolimab in combination with RAS inhibition in pancreatic ductal adenocarcinoma (PDAC) at the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development. The preclinical data were generated in a research study at Fred Hutch Cancer Center. The results show that the two approaches act on non-overlapping parts of PDAC biology, that the combination reshapes the tumor microenvironment, and reduces tumor burden. The findings emphasize the scientific rationale for Cantargia’s planned Phase 1b/2a study of nadunolimab in combination with a RAS inhibitor.
“RAS inhibitors target the mutations behind the great majority of pancreatic cancers, and they are changing what is possible in this disease. Even though RAS inhibitors such as Rasonque (daraxonrasib) will revolutionize the PDAC treatment landscape, there is still a major medical need, and the next advance will most probably come from combination therapies with RASi. In a research study performed by Prof Sita Kugel’s group at Fred Hutch, the combination of IL1RAP and RAS-directed therapies led to effects that were stronger than the individual parts. We believe this showcases the rationale for the clinical combination study we are preparing and strengthen the case for targeting RAS and IL1RAP at the same time.” said David Liberg, Chief Scientific Officer of Cantargia.
The poster focuses on the basal-like subtype of PDAC, the subtype associated with the poorest outcomes. The work identifies HMGA2 as a marker of this subtype and shows that it drives expression of IL-1α, which in turn activates fibroblasts and immune cells to build an immunosuppressive tumor microenvironment. Because IL1RAP is the co-receptor required for IL-1 signaling, nadunolimab’s target sits directly downstream of the biology that defines the most aggressive form of the disease.
In an HMGA2-positive, KRAS-mutated preclinical model, animals were treated with a mouse surrogate to nadunolimab and a RAS inhibitor, alone and in combination. In the tumor microenvironment, this led to reduced immune suppression and reduced tumor burden.
“HMGA2 defines a subtype of pancreatic cancer in which IL-1 signaling builds an intensely immunosuppressive tumor microenvironment,” said Dr. Sita Kugel, Fred Hutch Cancer Center, Seattle, USA. “In our model, RAS inhibition alone left that immune barrier largely intact; only when we added IL1RAP blockade did the suppressive myeloid and fibroblast populations recede and immune cells return to the tumor. Patients with this subtype have the poorest outcomes in pancreatic cancer. This combination goes directly after the biology that drives their disease and warrants evaluation in patients.”
Cantargia plans to evaluate the combination clinically in a Phase 1b/2a study of nadunolimab with a RAS inhibitor in PDAC.
The poster was presented at the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development in San Diego, USA.
Poster: B011 HMGA2 Expression in Pancreatic Ductal Adenocarcinoma Controls Tumor Microenvironment and Immunosuppression via IL1α
Session date: 27 September 2026, presented by Naomi Yamamoto, Fred Hutch Cancer Center, Seattle, WA, USA. Senior author: Dr. Sita Kugel.