Cantargia has reported new data providing further insights to the mechanisms underlying the antitumor activity of the IL1RAP-binding antibody nadunolimab (CAN04).

In a model of the pancreatic cancer (PDAC) microenvironment, nadunolimab potently reduced levels of various tumor-promoting molecules, in sharp contrast to an anti-IL-1β antibody which showed no such effects, reports the company in a press release. PDAC and non-small cell lung cancer (NSCLC) patients treated with nadunolimab and chemotherapy showed reductions in the same molecules.

“The results provide new and exciting insights into the unique anti-tumor properties of nadunolimab, and further illustrate the advantages of its dual action properties. The findings strongly support the upcoming randomized clinical trials of nadunolimab,” says Göran Forsberg, CEO of Cantargia.

Support clinical interim efficacy data

Both IL-1α and IL-1β signal via IL1RAP and contribute to tumor progression by triggering the release of molecules such as CXCL1 and CXCL5, which stimulate recruitment of immune suppressive cells to the tumor. The data reported confirm that both IL-1α and IL-1β cause a release of CXCL1, CXCL5 and additional related markers by human blood cells and cancer-associated fibroblasts (CAF). Furthermore, the data show that IL1RAP blockade by nadunolimab reduces these effects.

In the presence of PDAC cells, tumor-supporting CAF also release CXCL1, CXCL5 and other markers, and these are similarly attenuated by nadunolimab but not an anti-IL-1β antibody. The effect is highly relevant to nadunolimab’s activity in the clinic, states the company. In blood samples from PDAC and NSCLC patients treated with nadunolimab and chemotherapy in the phase I/IIa trial CANFOUR, levels of CXCL1 and CXCL5 were reduced compared to samples collected prior to therapy. Increased levels of CXCL1 and CXCL5 are linked to poor patient prognosis. Preclinical studies by others have also shown that antibody targeting of CXCL1 or CXCL5 results in antitumor efficacy, and blockade of these signaling pathways are evaluated in clinical trials of cancer.

The findings support the promising clinical interim efficacy data presented recently at the ASCO Annual Meeting 2022. In over 100 patients evaluated in the CANFOUR trial, nadunolimab in combination with chemotherapy results in higher efficacy than historical controls for chemotherapy alone. Cantargia is preparing the next steps in the late-stage clinical development of nadunolimab in PDAC and NSCLC. Nadunolimab will be included in the pivotal phase II/III clinical trial Precision PromiseSM, designed by Pancreatic Cancer Action Network (PanCAN), and a randomized trial in NSCLC is also planned for 2023.

Photo of Göran Forsberg: Håkan Sansberg/Cantargia