Cantargia

• Nadunolimab added to carboplatin and gemcitabine (GC) did not impact the safety profile of the chemotherapy and was well tolerated with neutropenia and asthenia as the most common side effects
• The primary endpoint, overall response rate (ORR), was similar in the nadunolimab plus carboplatin/gemcitabine treated group and the carboplatin/gemcitabine reference group

TRIFOUR is an exploratory open label randomized Phase 1b/2 clinical study conducted by the Spanish Breast Cancer Group (GEICAM). The objective is to evaluate early signals of efficacy of Cantargia’s IL1RAP antibody nadunolimab in TNBC, with unconfirmed ORR as primary endpoint. The ORR was 40% in the Ph2 study in the nadunolimab plus GC treated patients. As reference, the ORR in the GC group was 43%. Subgroup analyses of the data are ongoing.

The tolerability of the combination was acceptable and in line with previous trials combining nadunolimab and chemotherapy. Most common side effects in this trial were neutropenia and asthenia with no notable differences between the two study arms.

“TNBC is a heterogeneous and difficult to treat disease, with a high unmet medical need. We welcome the efforts to explore new treatments and appreciate the learnings we are making from the TRIFOUR study. We now await the outcome of further analyses from the study, including overall survival,” said Dr. Eva Carrasco, CEO of GEICAM.

“We are pleased to have the opportunity to collaborate with GEICAM and explore nadunolimab in the TNBC indication. While the preliminary ORR results of the Phase 2 part of the TRIFOUR trial do not match those obtained in the Phase 1b part of the trial, the study continues and we will now await the mature survival data.” said Damian Marron, interim CEO of Cantargia. “Following the signing of our CAN10 agreement earlier this week, we will be undertaking a detailed portfolio discussion to define our plans for the further development of nadunolimab”.

The TRIFOUR Ph1b/2 study first enrolled 15 patients in a preliminary phase 1b dose-ranging part, which showed an acceptable safety profile with promising efficacy including 73% unconfirmed ORR (60% confirmed) in first-line (1L) or second-line (2L) patients with metastatic TNBC. In the Phase 2 part of the trial, patients were randomized to two study groups with nadunolimab + GC treatment in the experimental group (n=51) and GC alone in the reference group (n=48). Nadunolimab (2.5 mg/kg) and GC were given twice per cycle in 3- or 4-week cycles. The objective of the study was to identify early signals of efficacy, with an internal GC group for reference.

RECIST 1.1 criteria were used to evaluate the preliminary ORR which was based on a minimum of 2 CT scans (approx. 3 months treatment) from the 97 TNBC patients included in the efficacy analyses. Among these, 20 patients (40%) showed unconfirmed complete response (CR) or partial response (PR) in the nadunolimab + GC arm vs. 20 patients (43%) in the chemotherapy arm. This data in 1L and 2L patients is higher than the historical response rate of approximately 30% reported for GC alone in 1L, 2L and third-line patients [1], and similar to 1L TNBC patients treated with chemotherapy alone [2].

Nadunolimab has been tested in over 300 patients with metastatic cancer. Previous data in pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) indications have shown promising results for nadunolimab in combination with chemotherapy in these indications [3,4], and nadunolimab is granted Fast Track designation from the U.S. Food and Drug Administration (FDA) in PDAC patients with high expression levels of IL1RAP. Nadunolimab is currently being tested in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in an investigator-initiated clinical study at The University of Texas MD Anderson Cancer Center.

More details of the TRIFOUR study will be communicated at an upcoming scientific conference.

References
[1] O’Shaughnessy, J Clin Oncol 2014, 32:3840-3847
[2] Cortes N Engl J Med 2022, 387: 217-226
[3] van Cutsem et al, Clin Cancer Res 2024, 30: 5293-5303
[4] Paulus et al, Lung Cancer 2025, https://doi.org/10.1016/j.lungcan.2025.108664