^
    7d
    1B-22-2: In Situ Immunomodulation with CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients W/ Unresectable and Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial primary completion date • Immunomodulating • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    Keytruda (pembrolizumab) • CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    2ms
    Personalized TCR-T: Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) (clinicaltrials.gov)
    P1, N=1, Active, not recruiting, Providence Health & Services | Enrolling by invitation --> Active, not recruiting | N=24 --> 1
    Enrollment closed • Enrollment change
    |
    CD4 (CD4 Molecule)
    |
    Keytruda (pembrolizumab) • CDX-1140
    5ms
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma) (clinicaltrials.gov)
    P1/2, N=22, Completed, Craig L Slingluff, Jr | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
    |
    CDX-1140 • Hiltonol (poly-ICLC)
    6ms
    CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer (clinicaltrials.gov)
    P1; N=45 --> 30
    Combination therapy • Enrollment change • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 IHC 22C3 pharmDx
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    8ms
    A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC) (clinicaltrials.gov)
    P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    Keytruda (pembrolizumab) • capecitabine • oxaliplatin • CDX-1140
    9ms
    A Maintenance Therapy Study of Odetiglucan With CDX-1140 in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1, N=5, Terminated, HiberCell, Inc. | N=45 --> 5 | Trial completion date: Apr 2027 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2025 --> Mar 2024; sponsor decision
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    CDX-1140 • Imprime PGG (odetiglucan)
    10ms
    Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients (clinicaltrials.gov)
    P2, N=16, Terminated, Washington University School of Medicine | N=24 --> 16 | Trial completion date: Mar 2024 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Nov 2023; Celldex decision
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    CDX-1140 • Mobista (CDX-301)
    11ms
    Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer (clinicaltrials.gov)
    P2, N=80, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • CDX-1140
    1year
    Harnessing the potential of CD40 agonism in cancer therapy. (PubMed, Cytokine Growth Factor Rev)
    In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them.
    Review • Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CD40 (CD40 Molecule) • CD40LG (CD40 ligand)
    |
    CDX-1140 • cifurtilimab (SEA-CD40) • dalnicastobart (LVGN7409) • mitazalimab (ADC-1013) • selicrelumab (RG7876) • sotigalimab (PYX-107)
    1year
    Phase I trial of pegylated liposomal doxorubicin chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer (SABCS 2023)
    This is a single arm phase I pilot study of liposomal doxorubicin, CDX-1140 (CD40 agonist monoclonal antibody), and CDX-301 (recombinant Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic TNBC. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line treatment for metastatic disease (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites (NCT05029999) and is currently open at University of Texas Southwestern Medical Center, Texas Oncology, University of Chicago, University of Texas San Antonio, Sarah Cannon Research Institute, and Johns Hopkins.
    Combination therapy • P1 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD40 (CD40 Molecule)
    |
    HER-2 negative • PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    1year
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma) (clinicaltrials.gov)
    P1/2, N=22, Active, not recruiting, Craig L Slingluff, Jr | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
    |
    CDX-1140 • Hiltonol (poly-ICLC)
    over1year
    FLT3 Ligand, CD40 Agonist Antibody, and Stereotactic Radiotherapy (clinicaltrials.gov)
    P1/2, N=5, Terminated, Albert Einstein College of Medicine | N=46 --> 5 | Trial completion date: Aug 2024 --> Aug 2022 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2022; Low accrual
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    docetaxel • CDX-1140 • Mobista (CDX-301)
    over1year
    A Maintenance Therapy Study of Odetiglucan With a CD40 Agonist (CDX-1140) in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
    P1, N=45, Recruiting, HiberCell, Inc. | N=30 --> 45 | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: Mar 2025 --> Nov 2025
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    CDX-1140 • Imprime PGG (odetiglucan)
    over1year
    CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov)
    P1; Trial completion date: Apr 2026 --> Apr 2025
    Combination therapy • Trial completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    over1year
    A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC) (clinicaltrials.gov)
    P1/2, N=60, Not yet recruiting, National Cancer Institute (NCI)
    New P1/2 trial • Combination therapy
    |
    Keytruda (pembrolizumab) • capecitabine • oxaliplatin • CDX-1140
    over1year
    A phase 1b, open-label, two-part safety, tolerability, and efficacy study of a soluble beta-glucan (odetiglucan) in combination with a CD40 agonistic monoclonal antibody (CDX-1140) in patients with metastatic pancreatic adenocarcinoma whose disease did not progress during first-line (1L) chemotherapy. (ASCO 2023)
    5 US sites will participate. Clinical trial information: NCT04834778.
    Clinical • P1 data • Combination therapy • Metastases
    |
    CD40 (CD40 Molecule)
    |
    CDX-1140 • Imprime PGG (odetiglucan)
    almost2years
    In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=18, Recruiting, University of Southern California | Not yet recruiting --> Recruiting
    Enrollment open • IO biomarker • Immunomodulating • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    almost2years
    CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov)
    P1; Trial completion date: Oct 2024 --> Apr 2026 | Trial primary completion date: Oct 2024 --> Apr 2025
    Combination therapy • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    2years
    Phase 1 trial of anthracycline chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer (SABCS 2022)
    CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre- treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites (NCT05029999).
    Combination therapy • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD40 (CD40 Molecule)
    |
    HER-2 negative • PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx
    |
    CDX-1140 • Mobista (CDX-301)
    over2years
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma) (clinicaltrials.gov)
    P1/2, N=22, Recruiting, Craig L Slingluff, Jr | N=44 --> 22
    Enrollment change
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
    |
    CDX-1140 • Hiltonol (poly-ICLC)
    over2years
    In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, University of Southern California | Trial completion date: Nov 2024 --> Sep 2025 | Trial primary completion date: Nov 2023 --> Sep 2024
    Trial completion date • Trial primary completion date • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    over2years
    CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov)
    P1; Not yet recruiting --> Recruiting
    Combination therapy • Enrollment open
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    over2years
    Phase 1 pilot study with dose expansion of chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer. (ASCO 2022)
    This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic triple-negative breast cancer. Key eligibility criteria are unresectable stage III or stage IV triple-negative breast cancer (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites.
    Combination therapy • P1 data • Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD40 (CD40 Molecule)
    |
    HER-2 negative • PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx
    |
    CDX-1140 • Mobista (CDX-301)
    over2years
    CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov)
    P1; Initiation date: Feb 2022 --> Jun 2022
    Combination therapy • Trial initiation date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 negative
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    almost3years
    Radio-immunotherapy (CDX-301, Radiotherapy, CDX-1140 and Poly-ICLC) for the Treatment of Unresectable or Metastatic Breast Cancer Patients (clinicaltrials.gov)
    P1, N=0, Withdrawn, Roswell Park Cancer Institute | N=36 --> 0 | Not yet recruiting --> Withdrawn
    Clinical • Enrollment change • Trial withdrawal • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    3years
    Radio-immunotherapy (CDX-301, Radiotherapy, CDX-1140 and Poly-ICLC) for the Treatment of Unresectable or Metastatic Breast Cancer Patients (clinicaltrials.gov)
    P1, N=36, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2022 --> Nov 2023
    Clinical • Trial completion date • Trial primary completion date • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    over3years
    CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov)
    P1, N=45, Not yet recruiting, University of Texas Southwestern Medical Center
    Clinical • New P1 trial • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 negative
    |
    pegylated liposomal doxorubicin • CDX-1140 • Mobista (CDX-301)
    over3years
    Agonistic CD40 Antibodies in Cancer Treatment. (PubMed, Cancers (Basel))
    The reduction in tumor growth and ability to reprogram the tumor microenvironment in preclinical models lays the foundation for clinical development of agonistic CD40 antibodies (APX005M, ChiLob7/4, ADC-1013, SEA-CD40, selicrelumab, and CDX-1140) that are currently being evaluated in early phase clinical trials. In this article, we focus on CD40 expression and immunity in cancer, agonistic human CD40 antibodies, and their pre-clinical and clinical development. With the broad pro-inflammatory effects of CD40 and its ligand on dendritic cells and macrophages, and downstream B and T cell activation, agonists of this pathway may enhance the anti-tumor activity of other systemic therapies.
    Review • Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CD40 (CD40 Molecule)
    |
    CD40 expression
    |
    CDX-1140 • Chi Lob 7/4 • cifurtilimab (SEA-CD40) • mitazalimab (ADC-1013) • selicrelumab (RG7876) • sotigalimab (PYX-107)
    4years
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (clinicaltrials.gov)
    P1/2, N=44, Recruiting, Craig L Slingluff, Jr | Initiation date: Sep 2020 --> Dec 2020
    Clinical • Trial initiation date
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
    |
    CDX-1140 • Hiltonol (poly-ICLC)
    4years
    Radio-immunotherapy (CDX-301, Radiotherapy, CDX-1140 and Poly-ICLC) for the Treatment of Unresectable or Metastatic Breast Cancer Patients (clinicaltrials.gov)
    P1, N=36, Not yet recruiting, Roswell Park Cancer Institute
    Clinical • New P1 trial • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    CDX-1140 • Hiltonol (poly-ICLC) • Mobista (CDX-301)
    4years
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (clinicaltrials.gov)
    P1/2, N=44, Recruiting, Craig L Slingluff, Jr | Not yet recruiting --> Recruiting | Trial completion date: Nov 2024 --> May 2025 | Initiation date: May 2020 --> Sep 2020 | Trial primary completion date: May 2024 --> Sep 2024
    Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
    |
    CDX-1140 • Hiltonol (poly-ICLC)
    over4years
    Mel66: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (clinicaltrials.gov)
    P1/2, N=44, Not yet recruiting, Craig L Slingluff, Jr
    Clinical • New P1/2 trial
    |
    BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
    |
    CDX-1140 • Hiltonol (poly-ICLC)