nadunolimab (CAN04) / Cantargia - LARVOL DELTA

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 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

Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment. (PubMed, J Immunother Cancer) - "Our study demonstrates that targeting IL1RAP on CAFs inhibits IL-1-induced chemokine secretion and recruitment of neutrophils and monocytes, thereby counteracting the immunosuppressive microenvironment in PDAC. These findings highlight the therapeutic potential of targeting IL1RAP in PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Transplantation • CAFs • IL1B • IL1RAP

Cantargia and GEICAM present updated phase 1 clinical data and new translational results on nadunolimab treatment in advanced triple negative breast cancer at San Antonio Breast Cancer Symposium (Cantargia Press Release) - P1b/2 | N=116 | TRIFOUR (NCT05181462) | Sponsor: Cantargia AB | "The TRIFOUR phase 1b part evaluated nadunolimab at 1 mg/kg (n=3) and 2.5 mg/kg (n=12) combined with gemcitabine and carboplatin (GC) in 15 previously treated aTNBC patients. Initial results were presented in 2023, and the updated results confirm an acceptable safety profile with a promising efficacy of 60% response rate, 6.2 months progression-free survival (PFS), and 12.8 months overall survival (OS)....These findings suggest that nadunolimab exerts beneficial effects on immune cells involved in tumor-promoting inflammation....The trial is currently enrolling patients for the randomized phase 2 part at the 2.5 mg/kg dose of nadunolimab with GC vs. only GC. Initial results for this part of the study are expected late H1 2025."

P1 data • P2 data • Trial status • Triple Negative Breast Cancer

Safety, efficacy and emerging biomarker data from the Phase Ib part of a Phase Ib/II clinical study of nadunolimab in combination with gemcitabine and carboplatin in patients with advanced triple negative breast cancer (TRIFOUR study) (SABCS 2024) - P1/2 | "Data from the PhIb TRIFOUR study indicate that nadunolimab at 2.5mg/kg, combined with gemcitabine plus carboplatin, has acceptable safety and tolerability and shows promising antitumor activity. Analyses of immune cell subsets and biomarkers showed potentially beneficial effects on cells and markers related to inflammation and immune response, such as decreased ANC and IL8. Characterization of aTNBC affirmed IL1RAP expression on tumor cells, cancer fibroblasts as well as tumor-associated and blood immune cells."

Biomarker • Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CXCL8 • IL1A • IL1B • IL1RAP

Antibody drug conjugate (ADC) payload-induced IL1 suggests potential for anti-IL1RAP therapy combination for enhanced treatment efficacy and prevention of neuropathy (SITC 2024) - "Methods In vitro cultures of breast cancer cells (MD-MDA-231), pancreatic cancer cells (BxPC-3), cocultures of BxPC-3 cells and CAF, human primary monocytes and mouse BMDMs were treated with chemotherapy, ADC payloads, the MMAE-conjugated ADC enfortumab-vedotin, IL1, nadunolimab or a murine surrogate antibody to nadunolimab...Focusing on neuropathy-related, microtubule targeting drugs; MMAE, DM4, paclitaxel and enfortumab-vedotin all induced IL1 in tumor cells and tumor cell-CAF cocultures...Targeting IL1RAP thus constitutes a potentially attractive therapeutic approach in combination with chemotherapy as well as with ADCs to overcome IL1 mediated tumor-promoting immune suppression and neuropathy. Ethics Approval The studies were approved by Lund-Malmö Ethics Board, approval number 00771-2020 and Skåne Transfusion medicine approval 2022:14 LUÖÖTT for the use of blood byproducts."

Clinical • Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • IL1A • IL1B • IL1RAP

TRIFOUR: Nadunolimab in Combination with Gemcitabine Plus Carboplatin in Patients with Advanced Triple Negative Breast Cancer. (clinicaltrials.gov) - P1/2 | N=116 | Recruiting | Sponsor: Cantargia AB | Trial primary completion date: Aug 2026 ➔ Jun 2025

BRCA Companion diagnostic • Combination therapy • Metastases • PARP Companion diagnostic • Trial primary completion date • 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

Cantargia presents promising preclinical results on nadunolimab with antibody-drug conjugates at major immuno-oncology conference (Cantargia Press Release) - "Cantargia...reported preclinical results on potential synergism between nadunolimab and antibody-drug conjugate (ADC) therapies....Cantargia’s new preclinical data shows that ADCs (or payloads) increase the expression of IL-1α and IL-1β when interacting with cancer cells, cancer-associated fibroblasts, or immune cells. In addition, the data also demonstrates potent inhibition of IL-1 signaling in these ADCs-treated cell culture systems when combined with a nadunolimab surrogate antibody. Furthermore, experiments reveal pronounced payload-driven neuropathic effects in a mouse model of neuropathy."

Preclinical • Oncology • Solid Tumor

Cantargia presents Phase 2 Clinical Data in Pancreatic Cancer with Nadunolimab at ESMO Gastrointestinal Cancer Congress 2024 (Cantargia Press Release) - P1/2a | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "Cantargia...announced that nadunolimab (CAN04) combination therapy results in advanced/metastatic pancreatic cancer (PDAC) will be presented at ESMO Gastrointestinal Cancer Congress 2024....In the CANFOUR trial, 73 first line PDAC patients were treated with nadunolimab and gemcitabine/nab-paclitaxel (GN). The median OS of 13.2 months is longer than OS reported in Phase 3 trials for GN alone (8.5-9.2 months), FOLFIRINOX (11.1 months), or NALIRIFOX (11.1 months). In patients with available baseline tumor biopsies IL1RAP expression was measured on tumor cells. A high expression of IL1RAP correlated with better efficacy outcomes including a median OS of 14.2 months vs. 10.6 months for the IL1RAP low subgroup (p=0.026; n=29 and 20, respectively)."

P2a data • Pancreatic Cancer

Cantargia’s Strong Phase 2 Clinical Data in Pancreatic Cancer with Nadunolimab Published in Clinical Cancer Research (ACCESSWIRE) - P1/2a | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "In the CANFOUR trial, 73 first line pancreatic cancer patients were treated with nadunolimab and gemcitabine/nab-paclitaxel (GN). The median OS of 13.2 months is longer than OS reported in Phase 3 trials for GN alone (8.5-9.2 months), FOLFIRINOX (11.1 months), or NALIRIFOX (11.1 months). In patients with available baseline tumor biopsies, IL1RAP expression was measured on tumor cells. A high expression of IL1RAP correlated with better efficacy outcomes including a median OS of 14.2 months vs. 10.6 months for the IL1RAP low subgroup (p=0.026; n=29 and 20, respectively). The 1-year survival rate in the IL1RAP high subgroup was 67% compared to 39% in the IL1RAP low subgroup."

P2a data • Pancreatic Ductal Adenocarcinoma

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

TRIFOUR: Nadunolimab in Combination with Gemcitabine Plus Carboplatin in Patients with Advanced Triple Negative Breast Cancer. (clinicaltrials.gov) - P1/2 | N=116 | Recruiting | Sponsor: Cantargia AB | Trial primary completion date: Aug 2024 ➔ Aug 2026

BRCA Companion diagnostic • Combination therapy • Metastases • PARP Companion diagnostic • Trial primary completion date • 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

Phase I/II trial shows promising efficacy of nadunolimab in combination with platinum doublet as second-line therapy in patients with NSCLC (ESMO 2024) - P1/2 | "Here, data are reported from the phase I/IIa clinical trial CANFOUR in NSCLC pts treated with nadunolimab and platinum doublet. Pts with advanced NSCLC, 1st or 2nd line (1L/2L), received nadunolimab at 1 (n=16), 2.5 (n=3) or 5 mg/kg (n=11) with cisplatin/gemcitabine, or at 2.5 mg/kg with carboplatin/pemetrexed (n=10). Nadunolimab plus platinum doublet shows promising efficacy in NSCLC pts. Pts who progressed on pembrolizumab retained an inflammatory profile, although with signs of immunosuppression, and responded strongly to nadunolimab and platinum doublet combination."

Clinical • Combination therapy • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD163 • CD8 • CXCL10 • CXCL9 • IFNG • IL1B • IL1RAP • NCAM1

Safety, tolerability, and efficacy of nadunolimab in combination with pembrolizumab in patients with solid tumors (ESMO 2024) - P1b | "Nadunolimab with pembrolizumab was safe and well tolerated in patients with advanced solid tumors. Prolonged survival was observed in a subset of patients with a distinct biomarker profile. The results support further development of nadunolimab in combination with PD-(L)1 inhibitor therapy."

Clinical • Combination therapy • IO biomarker • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD163 • IL1RAP • IL6

Cantargia presents positive results at ESMO Congress 2024 showing benefit of nadunolimab combination therapy in cancer after relapse on PD1-inhibitors (Cantargia Press Release) - P1/2a | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB |"The first trial, CANFOUR, investigated nadunolimab in combination with platinum doublet chemotherapy in 40 first- or second-line non-small cell lung cancer (NSCLC) patients. Stronger efficacy was seen in 2L pts (n=17) compared to 1L pts (n=23) (ORR 71% vs 44%; OS 15.7 vs 11.5 months). Biopsy analyses showed that the 2L pts had a higher number of IL1RAP-positive immune cells, CD163+ macrophages, CD56+ NK cells and CD8+ T cells in the tumor at baseline. Efficacy results were most pronounced in second line non-squamous pts (n=11; ORR 91%, OS 26.7 months; PFS 10.4 months) including two complete responders."

P1/2 data • Non Small Cell Lung Cancer

Cantargia presents positive results at ESMO Congress 2024 showing benefit of nadunolimab combination therapy in cancer after relapse on PD1-inhibitors (Cantargia Press Release) - P1b | N=19 | CIRIFOUR (NCT04452214) | Sponsor: Cantargia AB | "The second trial, CIRIFOUR, investigated nadunolimab combination therapy with pembrolizumab in 15 heavily pretreated patients who had previously progressed on pembrolizumab or nivolumab monotherapy or combination treatments. Nine patients had head and neck cancer, 5 NSCLC and 1 melanoma. In this trial, the median survival was 19.7 months and the disease control rate was 60%. Similar to the CANFOUR data, the strongest benefits were observed in the group of patients with a specific profile of immune and immunosuppressive cells in the tumor microenvironment."

P1 data • Head and Neck Cancer • Melanoma • Non Small Cell Lung Cancer

Cantargia: new data from two clinical studies strongly support nadunolimab efficacy after relapse on PD1-inhibitors (Cantargia Press Release) - P1b | N=19 | CIRIFOUR (NCT04452214) | Sponsor: Cantargia AB | "The second trial, CIRIFOUR, investigated nadunolimab combination therapy with pembrolizumab in 15 heavily pretreated patients who had previously progressed on pembrolizumab monotherapy or combination treatments. Nine patients had head and neck cancer, 5 NSCLC and 1 melanoma. In this trial, the median survival was 19.7 months and the disease control rate was 60%. Similar to the CANFOUR data, the strongest benefits were observed in the group of patients with a specific profile of immune and immunosuppressive cells in the tumor microenvironment. The combination therapy was well tolerated."

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

Cantargia: new data from two clinical studies strongly support nadunolimab efficacy after relapse on PD1-inhibitors (Cantargia Press Release) - P1/2a | N=167 | CANFOUR (NCT03267316) | Sponsor: Cantargia AB | "The first trial, CANFOUR, investigated nadunolimab in combination with platinum doublet chemotherapy in 40 first- or second-line non-small cell lung cancer, NSCLC, patients. Stronger efficacy was seen in 2L pts (n=18 in total; n=17 post-pembrolizumab) compared to 1L pts (n=22) (ORR 72% vs 41%; PFS 7.6 mo vs 6.7 mo, p = 0.038; OS 15.7 mo vs 11.5 mo). Biopsy analyses showed that 2L pts had a higher number of IL1RAP-positive immune cells, CD163+ macrophages, CD56+ NK cells and CD8+ T cells in the tumor at baseline. Efficacy results were most pronounced in second line non-squamous pts (n=12; ORR 92%, OS 28.9 mo; PFS 13.0 mo) including two complete responders. The data suggest that nadunolimab may mediate its anti-tumor activity by blocking tumor promoting cells within the TME."

P1/2 data • Non Small Cell Lung Cancer

Cantargia reports timelines for nadunolimab clinical trial…in…triple negative breast cancer (Cantargia Press Release) - "The first results on safety and short-term efficacy in the ongoing phase 2 clinical trial in triple negative breast cancer (TNBC), in collaboration with GEICAM, is expected during H1 2025. Based on the positive phase 1 clinical data previously presented for nadunolimab combination therapy in TNBC, the randomized, controlled phase 2 clinical trial in approximately 100 patients with TNBC is advancing even though recruitment temporarily slowed down during summer....Cantargia will present new clinical results using nadunolimab at the upcoming ESMO conference in Barcelona Sep 13-17, 2024. Details on the presentation will be disclosed when abstracts become public Sep 9, 2024."

Clinical data • P2 data • Trial status • Triple Negative Breast Cancer

Cantargia reports timelines for nadunolimab clinical trial…in leukemia… (Cantargia Press Release) - "The US FDA has granted MD Andersson Cancer Center the IND for nadunolimab related to the upcoming phase 1b/2a clinical trial of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with an estimate for trial initiation during Q4 2024....The new phase 1b/2a clinical trial is designed to investigate nadunolimab in up to 20 patients with AML and 20 with MDS. The trial is sponsored by a grant from the US Department of Defense, DOD, to The University of Texas MD Anderson Cancer Center which will be responsible for conducting the trial. More details on the trial, including estimated timelines will be disclosed once the trial has received full IRB approval, which is expected during Q3 2024...."

IND • Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

CANFOUR: A First-in-Human Study of CAN04 in Patients With Solid Malignant Tumors (clinicaltrials.gov) - P1/2 | N=167 | Completed | Sponsor: Cantargia AB | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • ALK • EGFR