Nadunolimab Earns FDA Fast-Track Designation in Metastatic PDAC

Nadunolimab's developer is creating a diagnostic test to identify patients with high IL1RAP expression for inclusion in future clinical studies.

The FDA has granted fast-track designation to anti-IL1RAP antibody nadunolimab (CAN04) as a frontline treatment in combination with gemcitabine and nab-paclitaxel for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) with high levels of IL1RAP, according to a news release from the drug’s developer, Cantargia.¹

Data from the phase 2a CANFOUR trial (NCT03267316) informed the FDA decision, with efficacy results published in Clinical Cancer Research, revealing a 2-year overall survival (OS) rate of 35% in the IL1RAP-high population.² Additional data revealed that this population had a median OS of 14.2 months (95% CI, 10.0-28.6) vs 10.6 months (95% CI, 4.8-12.6) among those with low IL1RAP expression (P = .012) as well as respective 1-year OS rates of 67% (95% CI, 46%-81%) vs 39% (95% CI, 18%-60%). Additionally, the median progression-free survival (PFS) was 7.4 months (95% CI, 3.7-11.0) vs 5.1 months (95% CI, 1.9-7.3) in the respective subgroups (P = .012).

Furthermore, treatment with nadunolimab plus gemcitabine and nab-paclitaxel elicited an objective response rate of 48% (95% CI, 29%-67%) in the IL1RAP-high population vs 30% (95% CI, 12%-54%) in those who with IL1RAP-low disease (P = .205). The median duration of response in the respective subgroups was 8.7 months (95% CI, 3.7-11.8) vs 5.6 months (95% CI, 3.9-not estimable; P = .074).

“The recognition from the FDA for our clinical and translational data on nadunolimab and the future path in pancreatic cancer is an outstanding development for Cantargia,” Damian Marron, CEO of Cantargia, said in the news release.¹ “The support from the FDA for the continued development of nadunolimab in the high-IL1RAP subset of [patients with] PDAC further strengthens our efforts to bring this potentially important new treatment to these patients who currently lack options.”

Patients 18 years or older with newly diagnosed, histologically or cytologically confirmed PDAC in the dose-escalation phase of the trial were treated with nadunolimab in a standard 3 + 3 design at 5.0 mg/kg and 7.5 mg/kg plus gemcitabine and nab-paclitaxel. After the maximum tolerated dose was established at 5.0 mg/kg, the cohort was expanded and the protocol was amended to add 2 parallel nonrandomized, alternative assignment expansion cohorts treated at 1.0 mg/kg and 2.5 mg/kg of nadunolimab for part 2 of the study.

Among 76 patients treated with the combination therapy, the mean age was 63.0 years (SD, 9.5) and 58% were male. A total of 97% had stage IV disease at study entry, and of 76 patients, 29 had IL1RAP-high status and 20 had IL1RAP-low status. The most common tumor sites at study entry included the liver (65%) and lymph nodes (50%), and the median CA 19-9 level was 550 U/mL (range, 1.0-105,000).

The primary end point of the trial was safety. Secondary end points included antitumor response, PFS, and OS.

In total, 100% of patients experienced treatment-emergent adverse effects (TEAEs), including 89% experiencing at least 1 grade 3 or 4 TEAE and 4% experiencing grade 5 TEAEs. Additionally, grade 3 or 4 TEAEs related to nadunolimab occurred in 75% of patients, there was 1 dose-limiting toxicity, and TEAEs led to dose continuation in 7% of patients.

The most common any-grade TEAEs included neutropenia (76%), fatigue (54%), anemia (51%), thrombocytopenia (39%), and vomiting (37%). Furthermore, the most common grade 3 or 4 TEAEs included neutropenia (66%), leukopenia (24%), γ-glutamyltransferase increases (17%), and anemia (15%).

The developer is creating a diagnostic test to identify patients with high IL1RAP expression for inclusion in future clinical studies.

References

1. Cantargia’s nadunolimab antibody awarded US FDA fast track designation. News release. Cantargia. June 11, 2025. Accessed June 12, 2025. https://tinyurl.com/46jvnv7f
2. Cutsem EV, Collignon J, Eefsen RL, et al. Efficacy and safety of the anti-IL1RAP antibody nadunolimab (CAN04) in combination with gemcitabine and nab-paclitaxel in patients with advanced/metastatic pancreatic cancer. Clin Cancer Res. 2024;30(23):5293-5303. doi:10.1158/1078-0432.CCR-24-0645