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    DRUG:

    nadunolimab (CAN04)

    i
    Other names: CAN04, CAN-04, anti-il-1rap mab
    Company:
    Cantargia
    Drug class:
    IL1RAP inhibitor
    Related drugs:
    4d
    TRIFOUR: Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. (clinicaltrials.gov)
    P1/2, N=116, Recruiting, Cantargia AB | Phase classification: P1b/2 --> P1/2
    Phase classification • Combination therapy • BRCA Companion diagnostic • PARP Companion diagnostic • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative
    |
    PD-L1 IHC 22C3 pharmDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    carboplatin • gemcitabine • nadunolimab (CAN04)
    6ms
    CANFOUR: A First-in-Human Study of CAN04 in Patients With Solid Malignant Tumors (clinicaltrials.gov)
    P1/2, N=167, Active, not recruiting, Cantargia AB | Recruiting --> Active, not recruiting | Trial completion date: Oct 2022 --> Dec 2023 | Trial primary completion date: Mar 2022 --> Dec 2023
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation
    |
    cisplatin • carboplatin • gemcitabine • albumin-bound paclitaxel • pemetrexed • nadunolimab (CAN04)
    9ms
    Phase Ib safety and efficacy of nadunolimab/gemcitabine/carboplatin in mTNBC (ESMO 2023)
    Neutropenia is the most frequent toxicity but does not limit treatment. The randomized phase 2 part is currently enrolling with the 2.5 mg/kg dose.
    Clinical • P1 data • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    carboplatin • gemcitabine • nadunolimab (CAN04)
    9ms
    CIRIFOUR: A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors (clinicaltrials.gov)
    P1b, N=19, Completed, Cantargia AB | Active, not recruiting --> Completed | N=39 --> 19 | Trial completion date: Sep 2024 --> Jun 2023 | Trial primary completion date: Sep 2024 --> Jun 2023
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed • nadunolimab (CAN04)
    10ms
    A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=40, Completed, Cantargia AB | Active, not recruiting --> Completed | Trial primary completion date: Mar 2023 --> Jun 2023
    Trial completion • Trial primary completion date • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
    |
    MSI-H/dMMR • KRAS wild-type • RAS wild-type
    |
    cisplatin • gemcitabine • docetaxel • 5-fluorouracil • oxaliplatin • leucovorin calcium • nadunolimab (CAN04)
    10ms
    CAPAFOUR: A Study of the Safety and Tolerance of CAN04 in Combination With FOLFIRINOX in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1b, N=25, Completed, Cantargia AB | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • nadunolimab (CAN04)
    12ms
    Safety, efficacy and biomarker data in non-small cell lung cancer patients treated with the anti-IL1RAP antibody nadunolimab in combination with platinum doublet. (ASCO 2023)
    Pts with advanced NSCLC, 1st line or progressed on pembrolizumab, received nadunolimab at 1 (n=16), 2.5 (n=3) or 5 mg/kg (n=11) with cisplatin/gemcitabine (NCG), or at 2.5 mg/kg with carboplatin/pemetrexed (NCP) (n=5). NCG shows promising efficacy in NSCLC with a trend for dose response, and long-term disease control by nadunolimab monotherapy post chemo with good safety. These observations are supported by changes in TME-related serum biomarkers. Preliminary data suggest similar efficacy with NCP, and in more heavily pretreated pts.
    Clinical • Combination therapy • PD(L)-1 Biomarker
    |
    CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • IL1B (Interleukin 1, beta) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • pemetrexed • nadunolimab (CAN04)
    1year
    A surrogate to the anti-IL1RAP antibody nadunolimab induces tumor microenvironment changes to the metastatic lung and reduces metastatic lesions in mouse models of metastatic cancer (AACR 2023)
    The effect on metastasis was not confined to the 4T1 model since a reduction of metastatic tumor cells after treatment with the mouse surrogate antibody was also observed in the murine B16-F10-luc i.v. model. Together these data indicate that targeting IL1RAP is an effective way to modulate the TME and counteract the suppressive environment in metastatic tissue, and ultimately may reduce the potential for metastatic tumors in cancer patients.
    Preclinical • Metastases
    |
    IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    nadunolimab (CAN04)
    1year
    Tumor IL1RAP levels and reduction in serum biomarkers correlate with response in PDAC patients treated with nadunolimab, an anti-IL1RAP monoclonal antibody, in combination with gemcitabine and nab-paclitaxel (AACR 2023)
    Nadunolimab combined with GN shows promising iPFS and OS in 73 PDAC patients. In these patients, high tumor cell expression of IL1RAP, the molecular target for nadunolimab, correlated with response. Reduction of the downstream biomarkers IL-6 and IL-8, as well as CRP, were most pronounced in responding patients and correlated with efficacy.
    Clinical • Combination therapy
    |
    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • IL1B (Interleukin 1, beta) • IL1RAP (Interleukin 1 Receptor Accessory Protein) • CRP (C-reactive protein)
    |
    IL1RAP overexpression
    |
    gemcitabine • albumin-bound paclitaxel • nadunolimab (CAN04)
    over1year
    CIRIFOUR: A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors (clinicaltrials.gov)
    P1b, N=39, Active, not recruiting, Cantargia AB | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed • nadunolimab (CAN04)
    over1year
    CAPAFOUR: A Study of the Safety and Tolerance of CAN04 in Combination With FOLFIRINOX in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1b, N=25, Active, not recruiting, Cantargia AB | Recruiting --> Active, not recruiting | Trial completion date: Aug 2023 --> Apr 2023 | Trial primary completion date: Jun 2023 --> Mar 2023
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • nadunolimab (CAN04)
    over1year
    CIRIFOUR: A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors (clinicaltrials.gov)
    P1b, N=39, Recruiting, Cantargia AB | N=15 --> 39 | Trial completion date: Jan 2022 --> Sep 2024 | Trial primary completion date: Jan 2022 --> Sep 2024
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed • nadunolimab (CAN04)
    over1year
    A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=40, Active, not recruiting, Cantargia AB | Recruiting --> Active, not recruiting | N=180 --> 40 | Trial completion date: Sep 2024 --> Apr 2023 | Trial primary completion date: Sep 2023 --> Mar 2023
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
    |
    MSI-H/dMMR • KRAS wild-type • RAS wild-type
    |
    cisplatin • gemcitabine • docetaxel • 5-fluorouracil • oxaliplatin • leucovorin calcium • nadunolimab (CAN04)
    over1year
    Nadunolimab inhibits IL-1α/β-induced CXCR1/2 ligand expression and reduces serum levels of CXCL1 and CXCL5 in NSCLC and PDAC patients (SITC 2022)
    Currently, nadunolimab is evaluated in phase II for PDAC and NSCLC ( NCT03267316 ) in combination with gemcitabine + Nab-paclitaxel or gemcitabine + cisplatin, respectively. Trial Registration NCT03267316 Ethics Approval The study was approved by the Ethics committees of the concerned countries and an informed consent was obtained from all individuals included in this study. Clinical trial number NCT03267316 .
    Clinical
    |
    CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • CXCR2 (Chemokine (C-X-C motif) receptor 2) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
    |
    cisplatin • gemcitabine • albumin-bound paclitaxel • nadunolimab (CAN04)
    over1year
    Blockade of IL-1α and IL-1β signaling by the anti-IL1RAP antibody nadunolimab (CAN04) mediates synergistic anti-tumor efficacy with chemotherapy. (PubMed, Cancer Immunol Immunother)
    Nadunolimab, and its surrogate antibody, synergize with platinum-based as well as non-platinum-based chemotherapy to induce potent anti-tumor effects, while blockade of only IL-1β signaling by anti-IL-1β antibody does not achieve this effect. In conclusion, blockade of IL1RAP with nadunolimab reduces IL-1-induced chemoresistance of tumors.
    Journal
    |
    IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    nadunolimab (CAN04)
    almost2years
    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)
    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 • P1/2 data • Combination therapy • PD(L)-1 Biomarker
    |
    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • pemetrexed • nadunolimab (CAN04)
    almost2years
    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)
    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 • P1/2 data • Combination therapy
    |
    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    gemcitabine • albumin-bound paclitaxel • nadunolimab (CAN04)
    almost2years
    Safety, tolerability, and preliminary efficacy of nadunolimab, a first-in-class monoclonal antibody against IL1RAP, in combination with pembrolizumab in subjects with solid tumors. (ASCO 2022)
    Fifteen pts received at least one dose of 5 mg/kg nadunolimab with pembrolizumab: median age 63 years (50-79), 27% female, 100% Stage IV, 93% and 7% received prior pembrolizumab or nivolumab respectively, 7% ECOG 0, 93% ECOG 1. The nadunolimab and pembrolizumab combination was considered safe and tolerable with preliminary evidence of prolonged disease control. The favorable safety provides basis for evaluation of further therapy with this combination. Next, nadunolimab and pembrolizumab will be assessed with carboplatin/pemetrexed in non-squamous NSCLC.
    Clinical • Combination therapy • PD(L)-1 Biomarker
    |
    IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL1RAP (Interleukin 1 Receptor Accessory Protein)
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • carboplatin • pemetrexed • nadunolimab (CAN04)
    2years
    TRIFOUR: Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. (clinicaltrials.gov)
    P1b/2; Not yet recruiting --> Recruiting
    Combination therapy • Enrollment open • BRCA Companion diagnostic • PARP Companion diagnostic
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative
    |
    PD-L1 IHC 22C3 pharmDx
    |
    carboplatin • gemcitabine • nadunolimab (CAN04)
    2years
    Molecular Basis of Selective Cytokine Signaling Inhibition by Antibodies Targeting a Shared Receptor. (PubMed, Front Immunol)
    IL-1RAcP has also been implicated in tumor progression in solid tumors and an anti-IL1RAP antibody (nadunolimab, CAN04) is in phase II clinical studies in pancreatic cancer and non-small cell lung cancer (NCT03267316)...Here, using functional, biophysical, and structural analyses, we show that antibodies specific for IL-1RAcP can differentially block signaling by IL-1 family cytokines depending on the distinct IL-1RAcP epitopes that they engage. Our results indicate that targeting a shared cytokine receptor is a viable therapeutic strategy for selective cytokine signaling inhibition.
    Journal
    |
    IL1B (Interleukin 1, beta) • IL33 (Interleukin 33)
    |
    nadunolimab (CAN04)
    over2years
    First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours. (PubMed, Br J Cancer)
    The IL1RAP targeting antibody CAN04 can be safely administered to patients up to 10.0 mg/kg weekly, which was defined as the RP2D. Serum biomarkers supported target engagement and IL-1 pathway inhibition.
    Clinical • P1 data • Journal
    |
    IL6 (Interleukin 6)
    |
    nadunolimab (CAN04)
    over2years
    A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=165, Recruiting, Cantargia AB
    Clinical • New P1/2 trial • Combination therapy
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
    |
    MSI-H/dMMR • KRAS wild-type • RAS wild-type
    |
    cisplatin • gemcitabine • docetaxel • 5-fluorouracil • oxaliplatin • leucovorin calcium • nadunolimab (CAN04)
    over2years
    CANFOUR: A First-in-Human Study of CAN04 in Patients With Solid Malignant Tumors (clinicaltrials.gov)
    P1/2, N=140, Recruiting, Cantargia AB | N=100 --> 140 | Trial completion date: Jun 2021 --> Oct 2022 | Trial primary completion date: Dec 2020 --> Mar 2022
    Clinical • Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation
    |
    cisplatin • gemcitabine • albumin-bound paclitaxel • nadunolimab (CAN04)
    over2years
    CAPAFOUR: A Study of the Safety and Tolerance of CAN04 in Combination With FOLFIRINOX in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1b, N=30, Recruiting, Cantargia AB | Not yet recruiting --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    5-fluorouracil • leucovorin calcium • nadunolimab (CAN04)
    over2years
    CAPAFOUR: A Study of the Safety and Tolerance of CAN04 in Combination With FOLFIRINOX in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1b, N=30, Not yet recruiting, Cantargia AB
    Clinical • New P1 trial • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    5-fluorouracil • leucovorin calcium • nadunolimab (CAN04)
    over3years
    A Study of the Safety and Tolerance of CAN04 in Combination With Pembrolizumab in Subjects With Solid Tumors (clinicaltrials.gov)
    P1b, N=15, Recruiting, Cantargia AB | Not yet recruiting --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    Keytruda (pembrolizumab) • nadunolimab (CAN04)
    almost4years
    A Study of the Safety and Tolerance of CAN04 in Combination With Pembrolizumab in Subjects With Solid Tumors (clinicaltrials.gov)
    P1b, N=15, Not yet recruiting, Cantargia AB
    Clinical • New P1 trial • Combination therapy
    |
    IL6 (Interleukin 6) • CRP (C-reactive protein)
    |
    Keytruda (pembrolizumab) • nadunolimab (CAN04)