Cantargia reported new clinical and biomarker data in further support of nadunolimab (CAN04) for treatment of pancreatic cancer (PDAC). Updated results in first-line combination with chemotherapy, as well as new results in late-stage monotherapy, show the strongest efficacy in patients with high levels of IL1RAP, the target of nadunolimab. Biomarker data consolidate these observations as levels of IL1RAP increase during PDAC development and appear to be linked to specific KRAS mutations associated with aggressive disease.

These data will be presented at the AACR Special Conference: Pancreatic Cancer 2023, 27-30 September. In the clinical phase I/IIa trial CANFOUR, a total of 23 late-stage PDAC patients received nadunolimab monotherapy, typically after failure on at least two previous chemotherapy regimens. Of these, IL1RAP levels were assessed in tumor biopsies taken before treatment from 17 patients, categorized as either IL1RAP high or IL1RAP low.

Notably, IL1RAP high patients had stronger clinical benefit compared to IL1RAP low patients, including prolonged median overall survival (5.8 vs 2.6 months; p=0.078) and progression-free survival (iPFS 3.6 vs 1.6 months; p=0.0073), indicating target engagement by nadunolimab leading to antitumor activity. Similar observations were made for the 73 first-line patients treated with a combination of nadunolimab and gemcitabine/nab-paclitaxel in CANFOUR, although as expected the median survival was generally longer compared to the late-stage patients. Significantly prolonged median overall survival was observed in IL1RAP high compared to IL1RAP low patients (14.2 vs 10.6 months; p=0.026), with a trend for higher response rates, with deeper and more durable responses.

These results are complemented by biomarker data obtained from publicly available gene databases, in collaboration with experts in PDAC, as well as molecular profiling data from pancreatic cancer patients included in the Know Your Tumor programme by Pancreatic Cancer Action Network (PanCAN). Collectively, the biomarker data show that levels of IL1RAP, as well as IL-1alpha and IL-1beta which signal via IL1RAP, are increased in PDAC tumors compared to healthy pancreas. Further, the highest levels of IL1RAP were observed in late-stage PDAC tumors, and patients with high IL1RAP levels had shorter overall survival.

Notably, high IL1RAP levels also correlated with the presence of KRAS mutations, in particular G12D, which is the most common KRAS mutation in PDAC. This is a key finding as KRAS mutations are considered a crucial component for disease progression in PDAC, and few effective therapies for targeting such mutations have been developed.