Nadunolimab Plus Chemotherapy Improves Survival in IL1RAP‑High Metastatic PDAC

The study analysis evaluated the efficacy of nadunolimab— a fully humanized Fc enhanced IgG1 monoclonal antibody targeting interleukin 1 receptor accessory protein (IL1RAP)—in combination with gemcitabine and nab paclitaxel for previously untreated, metastatic pancreatic ductal adenocarcinoma (PDAC) exhibiting elevated IL1RAP expression.

The US Food and Drug Administration granted fast track designation based on these findings. In the phase 2 CANFOUR trial (NCT03267316), 49 patients underwent baseline tumor biopsy for IL1RAP quantification.

Participants were stratified into high versus low IL1RAP expression cohorts and received standard dosing of gemcitabine (1000 mg/ m²) plus nab paclitaxel (125 mg/m²) on days 1, 8, and 15 of each 28 day cycle, concurrently with nadunolimab. Patients with high IL1RAP expression demonstrated a median overall survival (OS) of 14.2 months compared with 10.6 months in the low expression group (P = .012). Median progression free survival (PFS) was likewise extended (7.4 vs. 5.1 months; P = .012).

Overall response rates (ORR) favored the high expression cohort (48% vs. 30%; P = .205), albeit without statistical significance. These results indicate that IL1RAP expression may predict enhanced response to nadunolimab containing regimens; however, the small sample size and nonrandomized design warrant caution. Furthermore, development of a companion diagnostic is under way to optimize patient selection for future randomized studies.

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