Cantargia AB's nadunolimab (CAN04) in combination with gemcitabine and nab-paclitaxel (GN) has demonstrated promising efficacy in patients with advanced/metastatic pancreatic cancer (PDAC). The results, published in Clinical Cancer Research, indicate improved overall survival compared to historical data for chemotherapy alone, with a particularly strong effect observed in patients with high tumor levels of IL1RAP.
Improved Survival Outcomes
The Phase 2 CANFOUR trial treated 73 first-line pancreatic cancer patients with nadunolimab and GN. The median overall survival (OS) was 13.2 months, exceeding the OS reported in Phase 3 trials for GN alone (8.5-9.2 months), FOLFIRINOX (11.1 months), or NALIRIFOX (11.1 months). Notably, in patients with high IL1RAP expression, the median OS reached 14.2 months compared to 10.6 months in the IL1RAP low subgroup (p=0.026). The 1-year survival rate in the IL1RAP high subgroup was 67%, versus 39% in the IL1RAP low subgroup.
Neuroprotective Effect
An intriguing finding was the lower-than-expected incidence of peripheral neuropathy, a common side effect of chemotherapy. A statistically significant relationship (p=0.042) was observed between nadunolimab dose level and onset of neuropathy, suggesting a potential protective effect of nadunolimab against chemotherapy-induced neuropathy.
IL1RAP as a Target
Pancreatic cancer is characterized by a fibro-inflammatory microenvironment with upregulation of IL1RAP and tumor-promoting IL-1 signaling. Nadunolimab combines blockade of the IL-1 signaling pathway through IL1RAP inhibition with antibody-dependent cell-mediated cytotoxicity (ADCC) activity. These data suggest that nadunolimab may provide antitumor effects together with a protective effect when combined with chemotherapy.
Future Directions
"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," said Dominique Tersago, CMO of Cantargia. "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."
