Cantargia

“The efficacy results and the observed neuroprotective effect of nadunolimab are clearly intriguing. We are proud of this publication in one of the leading oncology journals and look forward to the increased visibility and upcoming steps in the development of nadunolimab,” said Göran Forsberg, CEO of Cantargia.

Patients with metastatic PDAC have a poor prognosis, and survival probability is <5% at 5 years. The fibro-inflammatory microenvironment which characterizes pancreatic cancer has a stroma infiltrated by cancer-associated fibroblasts and immune cells, creating an environment which involves upregulation of IL1RAP and tumor promoting IL-1 signaling with associated downstream pro-tumor cytokines. Nadunolimab combines blockade of the IL-1 signaling pathway through IL1RAP inhibition with a pronounced ADCC activity.

In the CANFOUR trial, 73 first line pancreatic cancer patients were treated with nadunolimab and gemcitabine/nab-paclitaxel (GN). The median OS of 13.2 months is longer than OS reported in Phase 3 trials for GN alone (8.5-9.2 months), FOLFIRINOX (11.1 months), or NALIRIFOX (11.1 months). In patients with available baseline tumor biopsies, IL1RAP expression was measured on tumor cells. A high expression of IL1RAP correlated with better efficacy outcomes including a median OS of 14.2 months vs. 10.6 months for the IL1RAP low subgroup (p=0.026; n=29 and 20, respectively). The 1-year survival rate in the IL1RAP high subgroup was 67% compared to 39% in the IL1RAP low subgroup. Addition of nadunolimab to GN was generally well tolerated, although with an increased incidence of grade 3/4 neutropenia and febrile neutropenia, unless managed with prophylactic use of growth factor support.

Notably, the incidence of peripheral neuropathy was lower than expected from chemotherapy treatment. It is likely that IL-1 driven inflammation plays a role in nab-paclitaxel induced neuropathy. Only one grade 3 event was recorded and a statistically significant (p=0.042) relationship between nadunolimab dose level and onset of neuropathy was observed. These data suggest that nadunolimab may confer a protective effect on the development of neuropathy.

“The efficacy and safety results, particularly the striking efficacy of the IL1RAP high subgroup as well as the lower than expected incidence of severe neuropathy highlight the potential of nadunolimab as a cancer therapy which may provide antitumor effects together with a protective effect when combined with chemotherapy. These results clearly warrant further development and we look forward to upcoming clinical studies with the aim to bring a much needed new treatment option to patients with metastatic pancreatic cancer.” said Dominique Tersago, CMO of Cantargia.

The publication, titled “Efficacy and safety of the anti-IL1RAP antibody nadunolimab (CAN04) in combination with gemcitabine and nab-paclitaxel in advanced/metastatic pancreatic cancer”, by Van Cutsem et al, is available online at the jounal’s website Clinical Cancer Research | American Association for Cancer Research (aacrjournals.org), and through a link at Cantargia’s website https://cantargia.com.

References
Von Hoff et al, N Engl J Med 2013; Wainberg et al, Lancet 2023: Conroy et al, NEJM 2011