nadunolimab (CAN04) / Cantargia - LARVOL DELTA

Cantargia Provides Update on Overall Survival Data from TRIFOUR (ACCESS Newswire) - "The analysis showed no difference in median overall survival (mOS) between the group treated with nadunolimab plus gemcitabine/carboplatin (GC) and the GC control group. Notably, both groups achieved a survival duration of 26 months, which exceeds historical expectations for this patient population. Earlier findings, reported in July 2025, showed no meaningful difference in the study's primary endpoint, overall response rate (ORR), between the treatment arms....Based on these results, Cantargia will discontinue further development in TNBC."

Discontinued • P1/2 data • Triple Negative Breast Cancer

AK135, a novel antagonistic antibody targeting IL-1RAP for CIPN therapy (SITC 2025) - "A CIPN model in B6-hIL1RAP transgenic mice were established via intermittent low-dose paclitaxel induction. Then the pharmacological efficacy of AK135 in this model was evaluated.Results AK135 shows high affinity to IL-1RAP and exhibits potent neutralizing bioactivity in IL-1/IL-33/IL-36 signaling pathways, while Nadunolimab (CAN04) has a weaker blocking effect on the IL-33 and IL-36 signaling pathways, as shown in table 1...Additionally, AK135 treatment led to a dose-dependent decrease in pain-related cytokines in spinal cord tissue homogenates, supporting its anti-inflammatory mechanism in pain relief.Conclusions As a potential chemotherapy companion drug, AK135 potently targets IL-1RAP to block IL-1/IL-33/IL-36-driven inflammatory signaling, mitigates proinflammatory cytokine release, and alleviates chemotherapy-induced peripheral neuropathy (CIPN) in preclinical models. Its dose-dependent efficacy in pain relief, coupled with good tolerability, underscores..."

Oncology • CXCL8 • IL1RAP • IL33 • IL6

Comparative Efficacy and Safety of Chemotherapeutic, Targeted, and Immunotherapy Drugs for Pancreatic Ductal Adenocarcinoma Treatment: A Network Meta-Analysis of RCTs (ACG 2025) - "Our analysis included 33 RCTs with a total sample size of 9,239 participants, comprising 5,636 in the treatment group and 3,603 in the control group. The included studies evaluated therapies such as Atezolizumab (79), Cabozantinib (76), Combined Chemotherapy (58), Demivistat + FOLFIRINOX (266), Durvalumab (3), EGPH20 + GEM-NABP (327), Erlotinib (518), FOLFIRINOX (433), Gemcitabine (2,090), Irinotecan (1,216), Mitazalimab (70), Nab-Paclitaxel (71), Nadunolimab (76), Napabucasin + GEM-NABP (565), Olaparib (124), Narilifox (766), Placebo (322), and Zenocutumab (454). The most significant survival benefit was observed with Irinotecan (OR = 4.96, 95% CI [1.45; 16.91],), while the least survival benefit was seen with Zenocutumab (OR = 0.38, 95% CI [0.03; 4.41],) compared to placebo."

Retrospective data • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Interleukin-1 Receptor Accessory Protein (IL1RAP) overexpression is associated with worse outcome in PDAC and can be reversed by nadunolimab treatment Free (AACRPanCa 2025) - P=N/A, P1/2 | "In the CANFOUR trial (NCT03267316), 73 patients with previously untreated, locally advanced or metastatic PDAC, received nadunolimab with gemcitabine/nab-paclitaxel (GN). IL1RAP expression is associated with oncogenic KRAS driver mutations and poor survival in PDAC. High expression of tumor cell IL1RAP is associated with worse outcomes in patients treated with GN, while the inverse is seen in patients treated with GN + nadunolimab. These data collectively suggest that IL1RAP is highly relevant in PDAC and associated with poor prognosis but can be meaningfully targeted by nadunolimab."

Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IL1RAP • KRAS

Exploiting Myeloid-Stromal IL1RAP as a Therapeutic Vulnerability to Improve Chemoimmunotherapy Sensitivity in Pancreatic Cancer Free (AACRPanCa 2025) - P1/2 | "Clinical outcomes in patients treated with anti-IL1RAP Ab nadunolimab (Nadu)+gemcitabine+nab-paclitaxel (GnP) in Phase II CANFOUR trial (NCT03267316) were stratified by immune and stromal IL1RAP expression; paired PDAC biopsies pre-/post-treatment were analyzed by mIF. IL1RAP-expressing myeloid-stromal networks may represent a distinct therapeutic barrier in PDAC, which can be disrupted pharmacologically to invigorate immunotherapy-permissive CD8+ T-cell subsets and improve chemoimmunotherapy sensitivity. These findings support an upcoming neoadjuvant trial combining nadunolimab with chemoimmunotherapy in patients with operable PDAC."

IO biomarker • Stroma • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD14 • CD69 • CD8 • GZMB • IL1RAP • IL2 • IL33 • ITGAM • KRAS

The first poster presentation focuses on tumor cell expression of IL1RAP and was performed in collaboration with Herlev Hospital, Copenhagen, Denmark. (ACCESS Newswire) - "The new data measures protein expression of IL1RAP on tumor cells in baseline biopsies from a similar cohort from the BIOPAC biobank treated with gemcitabine/nab-paclitaxel. In contrast to the CANFOUR data, patients with higher tumor cell expression of IL1RAP showed a shorter overall survival (8.5 vs 10.0 months; p=0.13) and lower 2-year survival (3.5% vs 18%) compared to patients with a low IL1RAP expression. This was even more pronounced in patients with KRAS mutations where IL1RAP high patients had a significantly shorter survival (7.8 vs 10.2 months, p=0.029). These data strengthen the results from the CANFOUR trial and highlight the relevance of targeting IL1RAP by nadunolimab."

Retrospective data • Pancreatic Ductal Adenocarcinoma

The second poster presentation shows groundbreaking work from the group of Dr. Jashodeep Datta at Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine in Miami, FL. (ACCESS Newswire) - "These data demonstrate potent effects of a mouse surrogate antibody of nadunolimab (m-nadunolimab) in a hard-to-treat preclinical model of aggressive KRAS-mutated PDAC. In addition, treatment with m-nadunolimab could break resistance to chemoimmunotherapy in this model, leading to enhanced T cell activation and a stronger, synergistic effect in combination with chemotherapy and anti-PD1 therapy. In human PDAC samples, IL1RAP expression was shown to be elevated in the PDAC tumor microenvironment and selectively enriched in chemotherapy resistant samples."

Preclinical • Pancreatic Ductal Adenocarcinoma

A Phase 1B/2A Trial of NADUNOLIMAB in Combination With Azacitidine (With/Without Venetoclax) in Patients With Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML) (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Cantargia granted important US patent for nadunolimab (Cantargia Press Release) - "The patent number is US 12,398,213 and the patent is valid until 2035 (excluding any patent term extension). The granted patent provides protection for method of treatment of Nadunolimab in combination with chemotherapy and/or immunotherapy."

Patent • Pancreatic Ductal Adenocarcinoma

Letter to the editor: Critical analysis of the CANFOUR trial on nadunolimab in advanced NSCLC. (PubMed, Lung Cancer) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety, efficacy, and analysis of biomarkers in patients with advanced non-small cell lung cancer treated with the anti-IL1RAP antibody nadunolimab (CAN04) in combination with platinum doublet. (PubMed, Lung Cancer) - P1/2 | "Nadunolimab plus platinum-based doublet chemotherapies showed promising efficacy in advanced NSCLC, with the greatest benefit in patients with non-squamous histology treated in second line after relapsing on pembrolizumab treatment."

Biomarker • Journal • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • IL1B • IL1RAP

Cantargia announces preliminary topline efficacy results from the phase 2 TRIFOUR trial of nadunolimab in advanced triple-negative breast cancer (TNBC) (Cantargia Press Release) - P1b/2 | N=117 | TRIFOUR (NCT051814620) | Sponsor: Cantargia AB | "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."

P2 data • Triple Negative Breast Cancer

Cantargia Announces Publication of Clinical Data Showing Benefit of Nadunolimab Combination Therapy in Advanced Lung Cancer (ACCESSWIRE) - P1/2a | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "Cantargia...announced the publication of results from the CANFOUR trial with nadunolimab in combination with chemotherapy in the peer reviewed journal Lung Cancer...The CANFOUR Phase 2a trial with 40 advanced/metastatic NSCLC patients investigated nadunolimab....Interestingly, highest efficacy was seen in patients previously treated with pembrolizumab (n=17) as compared to treatment naïve patients (n=23) (ORR 71% vs 44%; OS 15.7 vs 11.5 months). The 2L post-pembrolizumab patients had a markedly different tumor microenvironment at baseline with higher number of IL1RAP-positive immune cells, CD163+ macrophages, CD56+ NK cells and CD8+ T cells. Best response was seen in 2L non-squamous patients (n=11) which showed an outstanding ORR of 91%, PFS of 10.4 months and OS of 26.7 months, including two complete responders."

P2a data • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

Safety, efficacy, and analysis of biomarkers in patients with advanced non-small cell lung cancer treated with the anti-IL1RAP antibody nadunolimab (CAN04) in combination with platinum doublet (Lung Cancer) - P1/2 | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "43 patients were enrolled, median age 64 years, 38 % female, and 43 % were treated in second-line post-pembrolizumab. Median PFS was 7.2 months (95 %CI 5.6–9.2), median OS was 13.7 months (95 %CI 11.1–18.3), and 1-year survival was 54 %. The greatest benefits were observed in 11 patients with non-squamous histology treated in second-line post-pembrolizumab: median OS 26.7 months, ORR 91 % including two complete responders (with distinct biomarker profiles), and 1-year survival 82 %. Biomarker analyses showed that patients in second-line post-pembrolizumab had an enhanced level of tumor-infiltrating immune cells compared to treatment naïve patients."

Biomarker • P1/2 data • Non Small Cell Lung Cancer

Cantargia’s nadunolimab antibody awarded US FDA Fast Track Designation (Cantargia Press Release) - "Cantargia...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to nadunolimab, Cantargia’s anti-IL1RAP antibody for the treatment of patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) with high expression levels of IL1RAP in combination with gemcitabine and nab-paclitaxel. The FTD follows strong clinical data from the CANFOUR study showing a two-year survival of 35%, an overall survival (OS) of 14.2 months and overall response rate (ORR) of 48% in this patient population."

Evidence highlight • Fast track • Pancreatic Ductal Adenocarcinoma • IL1RAP

Cantargia’s announces publication of clinical data demonstrating potential of nadunolimab plus pembrolizumab in solid tumors (Cantargia Press Release) - P1 | N=19 | CIRIFOUR (NCT04452214) | Sponsor: Cantargia AB | "The CIRIFOUR trial investigated nadunolimab combination therapy with pembrolizumab in 15 heavily pretreated patients who had previously progressed on treatment with checkpoint inhibitors. Nine patients had head and neck cancer, five non-small cell lung cancer (NSCLC) and one melanoma. The combination therapy was safe and well tolerated, and with an encouraging median survival of 19.7 months and a disease control rate of 60%. The strongest benefits were observed in a group of patients with a specific immune profile with high baseline levels of macrophages and natural killer cells in the tumor microenvironment."

P1 data • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Adding nadunolimab to chemotherapy or antibody drug-conjugates (ADCs) may improve antitumor efficacy and counteract peripheral neuropathy (AACR 2025) - "Building on these promising findings, our aim was to further investigate nadunolimab's additional potential in mitigating neuropathies associated with chemotherapy and ADCs. The potential neuroprotective effect of nadunolimab was analyzed in two clinical trials: one involving 14 pts with 8 different cancer indications treated with FOLFOX and nadunolimab at 1 mg/kg (n=7) or 0.5 mg/kg (n=7), and another involving 18 PDAC pts treated with FOLFIRINOX and nadunolimab at doses of 0.5 mg/kg (n=8), 1 mg/kg (n=3), 1.5 mg/kg (n=4), and 2.5 mg/kg (n=3). In mice, neuropathy was induced by vincristine, nab-paclitaxel, nab-paclitaxel plus gemcitabine, or ADC payloads... Overall, our current findings in conjunction with previous results, suggest that nadunolimab may not only offer anti-tumor benefits but also protection against the neuro-inflammatory component driving chemotherapy- and ADC-induced neuropathy."

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • IL1RAP

Cantargia announces the publication of preclinical data highlighting nadunolimab's potential to counteract tumor-driven systemic immunosuppression (Cantargia Press Release) - "Cantargia...reported the publication of preclinical results in the renowned scientific journal Cancer Discovery, demonstrating that targeting IL1RAP can effectively inhibit tumor-induced systemic immune suppression in cancer by counteracting immune suppressive myeloid cells....The new preclinical data also revealed that a surrogate to Cantargia’s nadunolimab, which binds IL1RAP and blocks IL-1 family signaling, could abrogate the expansion of immunosuppressive neutrophils and slow tumor growth. Importantly, the nadunolimab surrogate enhanced the anti-tumor efficacy of a cancer vaccine and increased the number of tumor-reactive T cells generated in response to the vaccine."

Preclinical • Oncology

Safety, tolerability, and preliminary efficacy of nadunolimab, an anti-IL- 1 receptor accessory protein monoclonal antibody, in combination with pembrolizumab in patients with solid tumors. (PubMed, Invest New Drugs) - P1b | "Nadunolimab with pembrolizumab had an acceptable safety profile, and prolonged disease control was observed in a subset of patients. The results support further development of nadunolimab in combination with checkpoint inhibitors."

Journal • Febrile Neutropenia • Gastrointestinal Disorder • Head and Neck Cancer • Hematological Disorders • Lung Cancer • Melanoma • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD163 • IL1B • IL1RAP • IL6

Cantargia presents association between nadunolimab and reduction of chemotherapy induced peripheral neuropathy (CIPN) at AACR (Cantargia Press Release) - P1 | N=25 | CAPAFOUR (NCT04990037) | P1/2 | N=40 | CESTAFOUR (NCT05116891) | Sponsor: Cantargia AB | "In line with the data in the CANFOUR trial, analysis of data in the CESTAFOUR (nadunolimab in combination with FOLFOX) and CAPAFOUR (nadunolimab in combination with mFOLFIRINOX) trials in advanced solid tumor indications further supports nadunolimab’s potential neuroprotective role. In both clinical trials, an association between higher doses of nadunolimab and lower incidence and later onset of CIPN was observed. Furthermore, preclinical data showed that a mouse-specific nadunolimab surrogate antibody prevented neuropathy induced by the chemotherapeutic agents nab-paclitaxel, gemcitabine, vincristine, as well as the combination of nab-paclitaxel and gemcitabine."

P1 data • P1/2 data • Preclinical • Biliary Tract Cancer • Cholangiocarcinoma • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Cantargia publishes an abstract on parallel anti-tumor activity and reduction of chemotherapy-induced neuropathy with nadunolimab (Cantargia Press Release) - P1/2a | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "The anti-tumor efficacy of nadunolimab in metastatic pancreatic cancer (PDAC) is strongly supported by the outcomes observed in the CANFOUR Phase 2 study (NCT03267316), where the 60% of patients that had high IL1RAP expression showed a 48% ORR and 14.2 months OS. Beyond tumor control, higher nadunolimab doses were associated with both a lower incidence and a delayed onset of chemotherapy-induced peripheral neuropathy (CIPN)....Nadunolimab’s additional potential in mitigating neuropathy demonstrated by data from Cantargia’s CESTAFOUR and CAPAFOUR clinical studies....Complementary preclinical studies showed that combining a nadunolimab surrogate antibody with various chemotherapy drugs completely inhibited CIPN in mouse models, highlighting IL1RAP-driven neuroinflammation as a potential underlying mechanism driving CIPN."

P1/2 data • Pancreatic Ductal Adenocarcinoma

TRIFOUR: Nadunolimab in Combination with Gemcitabine Plus Carboplatin in Patients with Advanced Triple Negative Breast Cancer. (clinicaltrials.gov) - P1/2 | N=117 | Active, not recruiting | Sponsor: Cantargia AB | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • ER • HER-2 • PD-L1 • PGR

First patient enrolled in Cantargia’s leukemia study with nadunolimab (Cantargia Press Release) - "Cantargia...announced that the first subject has been enrolled in a study with patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). This phase 1b/2a study is an investigator-initiated clinical study and will investigate safety and early efficacy after treatment with nadunolimab and standard of care chemotherapy. A total of 40 subjects including up to 20 for AML and 20 for MDS are estimated to be enrolled in the trial. Full recruitment is expected in 2027....The primary objective of this study is to evaluate safety and the recommended dosage of nadunolimab in combination with standard chemotherapies for leukemia (azacitidine and/or venetoclax)."

Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Cantargia’s TRIFOUR phase 2 study investigating nadunolimab in triple negative breast cancer fully recruited (Cantargia Press Release) - "Cantargia...today announced that all patients in the TRIFOUR clinical study are recruited. This phase 1b/2 study in advanced triple-negative breast cancer (TNBC) patients focuses on evaluating the efficacy of nadunolimab (CAN04) in combination with platinum-based chemotherapy compared to a control group receiving the same regime of chemotherapy alone. The first preliminary analysis of the primary objective, overall response rate (ORR), is expected in mid-2025."

P1/2 data • Trial status • Triple Negative Breast Cancer

Cantargia publishes strong preclinical effects and clinical monotherapy results on nadunolimab in pancreatic cancer in Journal for Immunotherapy of Cancer (Cantargia Press Release) - P1/2 | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "Cantargia...announced the publication of preclinical and clinical results using the IL1RAP targeted antibody nadunolimab (CAN04) in pancreatic cancer (PDAC). Nadunolimab had pronounced effects on PDAC associated fibroblasts and inhibited recruitment of tumor promoting immune cells....The relevance of these preclinical results could be linked to clinical results using nadunolimab monotherapy in the CANFOUR study. In late stage metastatic PDAC patients, high tumor baseline levels of IL1RAP strongly correlate with increased progression free survival (IL1RAP high vs low: 3.5 vs 1.2 months; p=0.0023) and a trend for survival advantage (5.0 vs 2.2 months) with a follow up of 11.5 months."

P1/2 data • Preclinical • Pancreatic Ductal Adenocarcinoma