nadunolimab (CAN04) / Cantargia - LARVOL DELTA

A phase 1b/2 study of toripalimab and nadunolimab for the treatment of chemotherapy-refractory metastatic microsatellite stable (MSS) colorectal cancer (CRC) (AACR 2026) - "Abstract is embargoed at this time."

Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor

New Preclinical Data on Anti-Tumor Effects of Nadunolimab in Metastatic Colorectal Cancer Presented at the Keystone Cancer Immunotherapy Conference (Yahoo Finance) - "The new preclinical results further indicate that IL1RAP dependent signaling is part of an immunosuppressive axis within both the primary tumor and metastatic sites...Combining the nadunolimab surrogate antibody with anti-PD-1 immune-checkpoint inhibitors showed a synergistic effect by reducing tumor burden in a CRC model that is otherwise unresponsive to immunotherapy. Disruption of this immune suppressive axis presents a unique opportunity to overcome resistance to immunotherapy, which has the potential to transform outcomes for metastatic MSS CRC patients."

Preclinical • Colorectal Cancer

Immunoprevention for High-risk Lung Lesions (clinicaltrials.gov) - P2 | N=59 | Recruiting | Sponsor: Robert Samstein | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2025 ➔ Apr 2026

Enrollment open • Trial initiation date

Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Dan Feng | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor • MSI

Cantargia Reports First Patient Dosed in New US Investigator-Initiated Colorectal Cancer Study (Yahoo Finance) - "The new phase 1b/2a investigator-initiated trial will be conducted at Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. The study (NCT07281716), led by principal investigator Dr. Dan Feng, is designed to investigate nadunolimab in combination with an anti-PD-1 inhibitor in up to 24 patients with MSS CRC. In addition to investigating anticancer effects, the study will include a comprehensive biomarker assessment package."

Trial status • Colorectal Cancer

Phase 1/2a trial of nadunolimab, a first-in-class fully humanized monoclonal antibody against IL1RAP, in combination with cisplatin and gemcitabine (CG) in patients with non-small cell lung cancer (NSCLC). (ASCO 2022) - P1/2 | " Patients (pts) with unresectable, locally advanced or metastatic NSCLC, progressed on pembrolizumab or in first line for advanced disease, were eligible. Nadunolimab combined with CG shows manageable safety and promising efficacy with a response rate of 53% in NSCLC pts. Nadunolimab is currently evaluated in several clinical trials investigating chemotherapy or IO combinations, including carboplatin and pemetrexed in non-squamous NSCLC."

Clinical • Combination therapy • P1/2 data • Anemia • Febrile Neutropenia • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • CSF3 • CXCL8 • IL1B • IL1R1 • IL1RAP • IL6

Phase 1/2a trial of nadunolimab, a first-in-class fully humanized monoclonal antibody against IL1RAP, in combination with gemcitabine and nab-paclitaxel (GN) in patients with pancreatic adenocarcinoma (PDAC). (ASCO 2022) - P1/2 | "Nadunolimab combined with GN shows promising iPFS and OS and manageable safety in PDAC pts. A phase 2/3 trial of nadunolimab combined with chemotherapy in PDAC is planned and nadunolimab is also currently evaluated in additional combination trials with chemotherapy or IO."

Clinical • Combination therapy • P1/2 data • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pain • Pancreatic Adenocarcinoma • Pancreatic Cancer • CSF3 • CXCL8 • IL1B • IL1R1 • IL1RAP • IL6

Efficacy and safety of the anti-IL1RAP antibody nadunolimab (CAN04) in combination with gemcitabine and nab-paclitaxel in patients with advanced/metastatic pancreatic cancer. (PubMed, Clin Cancer Res) - "Nadunolimab combined with GN shows promising efficacy and manageable safety in locally advanced/metastatic PDAC. Higher tumor baseline IL1RAP expression correlated with better outcome."

Combination therapy • Journal • Metastases • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pain • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CXCL8 • IL1B • IL1RAP

Myeloid-stromal IL1RAP as a therapeutic vulnerability in pancreatic cancer: Rationale for a neoadjuvant chemoimmunotherapy clinical trial. (ASCO-GI 2026) - P1/2 | "Combination CAN04, gemcitabine+nab-paclitaxel (GnP), and anti-PD1 therapy was tested in survival studies. 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 CAN04 with chemoimmunotherapy in patients with operable PDAC."

Clinical • IO biomarker • Stroma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD14 • CD69 • CD8 • GZMB • IL1RAP • IL2 • ITGAM • KRAS

Immunoprevention for High-risk Lung Lesions (clinicaltrials.gov) - P2 | N=59 | Not yet recruiting | Sponsor: Robert Samstein

New P2 trial

Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Dan Feng

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

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