Cantargia

“The new results put an additional exciting perspective on nadunolimab as it highlights a relationship between tumor promoting KRAS mutations and the tumor promoting signals nadunolimab has been designed to counteract. This gives further support on the importance of the nadunolimab data generated in pancreatic cancer,” said Göran Forsberg, CEO of Cantargia.

Patients with metastatic PDAC have a poor prognosis, and survival probability is <5% at 5 years. The disease is often associated with tumor promoting KRAS mutations. The tumor microenvironment in pancreatic cancer has a stroma with 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. The new data show a correlation between KRAS mutations and an activated IL-1 system, a signaling pathway nadunolimab has been designed to counteract.

In the CANFOUR trial, 73 first line PDAC 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)(1). 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).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. IL-1 driven inflammation likely plays a role in paclitaxel induced neuropathy. Only one grade 3 event was observed and a statistically significant (p=0.042) relationship between dose level and onset of neuropathy was observed. These data suggest that nadunolimab may confer a protective effect on the development of neuropathy.

The abstract has been published on the conference website, the poster will be presented June 27. It will also be available at the Cantargia website when presented at the conference

Reference:
1) OS 8.5 mo, PFS 5.3 mo, (Von Hoff et al, N Engl J Med 2013); OS 9.2 mo, PFS 5.6 mo, (Wainberg et al, Lancet 2023)