^
    9d
    A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T proliferation and anti-tumor immunity in mice. (PubMed, Nat Commun)
    In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients.
    Preclinical • Journal
    |
    CD8 (cluster of differentiation 8) • CD40 (CD40 Molecule)
    |
    CD40 expression
    15d
    Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as Single Agent and Combination Therapies in Advanced or Metastatic Malignancy (clinicaltrials.gov)
    P1, N=126, Active, not recruiting, Lyvgen Biopharma Holdings Limited | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025
    Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    dalnicastobart (LVGN7409) • exlinkibart (LVGN6051) • pradusinstobart (LVGN3616)
    18d
    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
    29d
    First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. (PubMed, J Immunother Cancer)
    This phase 1a study provided initial proof-of-mechanism for NG-350A, with strong evidence of tumor delivery, viral replication and transgene expression-particularly after intravenous dosing. The lack of transgene-related or off-target viral toxicity was consistent with the highly selective delivery and replication of NG-350A, even after systemic delivery. The efficacy of intravenous-dosed NG-350A will now be evaluated in combination with pembrolizumab (NCT05165433), as well as with chemoradiotherapy (NCT06459869).
    Clinical data • P1 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD40 (CD40 Molecule)
    |
    CD40 expression
    |
    Keytruda (pembrolizumab) • NG-350A
    1m
    The novel and potent CD40 agonist KHK2840 augments the antitumor efficacy of anti-PD-1 antibody and paclitaxel. (PubMed, Cancer Sci)
    Finally, a toxicology study in cynomolgus monkeys demonstrated that KHK2840 activated the CD40 signal with tolerable toxicological properties. These results indicate that KHK2840 is a novel and potent hCD40 agonistic antibody for cancer immunotherapy, which is expected to augment the antitumor efficacy of ICIs and chemotherapy.
    Journal
    |
    CD40 (CD40 Molecule)
    |
    paclitaxel
    1m
    CD40 agonist mitazalimab combined with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): updated efficacy and correlative biomarkers from the OPTIMIZE-1 trial (SITC 2024)
    These encouraging results from OPTIMIZE-1 form the basis of a future randomized confirmatory trial of mitazalimab in combination with mFOLFIRINOX in mPDAC. Ethics Approval The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines as defined by the International Conference on Harmonisation, in 14 European University Hospitals according to the study protocol and amendments, approved by local Institutional Review Boards and independent ethics committees: France:Comité de protection des personnes Est I, Centre hospitalier la Chartreuse - 1 Bld Chanoine Kir, BP 23314 21033 DIJON France Belgium: CHU UCL Namur, site Godinne, Comité d'éthique, Avenue Docteur G. Thérasse 1, 5530 YVOIR Spain: The CEIm of the Ramón y Cajal University Hospital, Madrid, Spain Patients provided written informed consent before enrolment.Download figure Open in new tab Download powerpoint Abstract 592 Figure 1 OPTIMIZE-1 dosing regimen and biomarker planView this table:View inline View popup Download powerpoint Abstract 592 Table 1 OPTIMIZE-1 outcomes
    Clinical • IO biomarker • Metastases
    |
    IFNG (Interferon, gamma) • CD40 (CD40 Molecule)
    |
    TruSight Oncology 500 Assay
    |
    5-fluorouracil • irinotecan • leucovorin calcium • mitazalimab (ADC-1013)
    1m
    SL03-OHD-105: Phase 1b Study of SL-172154 Administered with Combination Agent(s) in Subjects with Ovarian Cancers (clinicaltrials.gov)
    P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Trial completion date: Apr 2025 --> Nov 2024
    Trial completion date
    |
    FOLR1 ( Folate receptor alpha )
    |
    FOLR1 expression
    |
    pegylated liposomal doxorubicin • Elahere (mirvetuximab soravtansine-gynx) • SL-172154
    1m
    SL03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects with MDS or AML (clinicaltrials.gov)
    P1, N=160, Active, not recruiting, Shattuck Labs, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Apr 2025 --> Nov 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    Venclexta (venetoclax) • azacitidine • SL-172154
    2ms
    Study to Evaluate Adverse Events and Change in Disease Activity When Intravenous (IV) Infusion of ABBV-927 is Administered in Combination With IV Modified FOLFIRINOX (mFFX) With or Without IV Budigalimab Compared to mFFX in Adult Participants With Untreated Pancreatic Cancer Metastasis (clinicaltrials.gov)
    P1/2, N=40, Terminated, AbbVie | Completed --> Terminated; Strategic considerations
    Trial termination
    |
    5-fluorouracil • oxaliplatin • irinotecan • budigalimab (ABBV-181) • leucovorin calcium • giloralimab (ABBV-927)
    2ms
    A phase 1 study of the CD40 agonist MEDI5083 in combination with durvalumab in patients with advanced solid tumors. (PubMed, Immunotherapy)
    MEDI5083 maximum tolerated dose was 5 mg. Objective response rate was 2.8% (1 partial response and 11 stable disease). MEDI5083 toxicity profile limits its further development.
    P1 data • Journal • Combination therapy • Metastases
    |
    CD40 (CD40 Molecule)
    |
    Imfinzi (durvalumab) • MEDI5083
    2ms
    A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors (clinicaltrials.gov)
    P1, N=30, Recruiting, Genmab | Trial completion date: Oct 2027 --> Feb 2027
    Trial completion date • Combination therapy
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • 5-fluorouracil • GEN1042
    3ms
    A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=150, Active, not recruiting, AbbVie | Trial completion date: Sep 2024 --> Mar 2025 | Trial primary completion date: Sep 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    carboplatin • albumin-bound paclitaxel • budigalimab (ABBV-181) • giloralimab (ABBV-927) • revdofilimab (ABBV-368)
    3ms
    Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY) (clinicaltrials.gov)
    P1, N=198, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1
    Enrollment closed • Phase classification • Combination therapy • Metastases • Viral vector
    |
    Keytruda (pembrolizumab) • NG-350A
    3ms
    SL03-OHD-105: Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers (clinicaltrials.gov)
    P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Trial primary completion date: Jul 2024 --> Dec 2024
    Trial primary completion date
    |
    FOLR1 ( Folate receptor alpha )
    |
    pegylated liposomal doxorubicin • Elahere (mirvetuximab soravtansine-gynx) • SL-172154
    4ms
    CD40 Agonist and PD-1 Inhibitor in HNSCC (clinicaltrials.gov)
    P1, N=20, Recruiting, University of Pennsylvania | Not yet recruiting --> Recruiting
    Enrollment open
    |
    dalnicastobart (LVGN7409) • pradusinstobart (LVGN3616)
    4ms
    A Study of NWY001 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=196, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting | Initiation date: Oct 2023 --> Jan 2024
    Enrollment open • Trial initiation date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability)
    4ms
    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)
    4ms
    TQB2916 Injection Combined With Chemotherapy or Penpulimab Injection in the Treatment of Solid Tumors (clinicaltrials.gov)
    P2, N=54, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
    New P2 trial
    |
    doxorubicin hydrochloride • Anniko (penpulimab)
    4ms
    OPTIMIZE-1: Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients (clinicaltrials.gov)
    P1/2, N=94, Active, not recruiting, Alligator Bioscience AB | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    5-fluorouracil • irinotecan • mitazalimab (ADC-1013)
    4ms
    APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma (clinicaltrials.gov)
    P1, N=42, Completed, Yale University | Active, not recruiting --> Completed | Trial completion date: Oct 2027 --> May 2024
    Trial completion • Trial completion date • Combination therapy • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD163 (CD163 Molecule) • IL10 (Interleukin 10) • CD40LG (CD40 ligand)
    |
    Opdivo (nivolumab) • cabiralizumab (BMS-986227) • sotigalimab (PYX-107)
    5ms
    CD40 agonist engineered immunosomes modulated tumor microenvironment and showed pro-immunogenic response, reduced toxicity, and tumor free survival in mice bearing glioblastoma. (PubMed, Biomaterials)
    To overcome these issues, in this study, we have developed a multifunctional Immunosome where αCD40 is conjugated on the surface and RRX-001, a small molecule immunomodulator was encapsulated inside it...In addition, Immunosomes treated long-term surviving mice showed tumor specific immune memory response which prevented tumor growth upon rechallenge. Our results suggested that this novel formulation can be further explored in clinics to improve in vivo anti-tumor efficacy of αCD40 with long-lasting tumor specific immunity while reducing the associated toxicities.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • CD40 (CD40 Molecule) • IL4 (Interleukin 4) • ITGAX (Integrin Subunit Alpha X) • CD86 (CD86 Molecule)
    |
    nibrozetone (RRx-001)
    5ms
    Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, University of California, San Diego | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    mitazalimab (ADC-1013)
    5ms
    A Study of APX005M in Combination With Nivolumab and Ipilimumab in Treatment Naïve Patients With Advanced Melanoma or Renal Cell Carcinoma (RCC) (clinicaltrials.gov)
    P1, N=26, Active, not recruiting, Yale University | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • sotigalimab (PYX-107)
    5ms
    A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=163, Active, not recruiting, AbbVie | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    budigalimab (ABBV-181) • giloralimab (ABBV-927)
    5ms
    Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer. (PubMed, Res Sq)
    In a humanized mouse model for CD40 and FcγRs, 2141-V11 induced TLS formation in mice bearing orthotopic breast carcinoma, correlating with local and abscopal antitumor effects, systemic immune activation, and immune memory. These findings support the safety and efficacy of 2141-V11, warranting phase 2 studies and suggesting a unique mechanism of action for this Fc-enhanced immunotherapy (NCT04059588).
    Journal • Metastases
    |
    CD40 (CD40 Molecule)
    5ms
    FORTRESS: NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (clinicaltrials.gov)
    P1, N=30, Not yet recruiting, Akamis Bio
    New P1 trial • Combination therapy • Metastases • Viral vector
    |
    capecitabine • NG-350A
    5ms
    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)
    5ms
    D2C7-IT + 2141-V11 Combination Post-rection in rGBM - Phase 1b (clinicaltrials.gov)
    P1/2, N=46, Not yet recruiting, Darell Bigner
    New P1/2 trial
    |
    D2C7
    5ms
    Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study. (PubMed, Lancet Oncol)
    Mitazalimab with mFOLFIRINOX demonstrated manageable safety and encouraging activity, warranting continued development in a phase 3, randomised, controlled trial. The results from OPTIMIZE-1 pave the way for further exploration and confirmation of a novel immunotherapy treatment regimen for metastatic pancreatic ductal adenocarcinoma, which is a complex and aggressive cancer with very low survival rates and restricted treatment options.
    P1/2 data • Journal • Metastases
    |
    CD40 (CD40 Molecule)
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • mitazalimab (ADC-1013)
    6ms
    The engineered agonistic anti-CD40 antibody potentiates the antitumor effects of β-glucan by resetting TAMs. (PubMed, Immunol Lett)
    Furthermore, the abundance of Faecalibaculum, one of the probiotics critical for tumor suppression, was obviously increased in the combination of 5C11 and β-glucan-treated mice. These data reveal a novel mechanism of tumor suppression upon the combination treatment of 5C11 and β-glucan and propose that the combination treatment of agonistic anti-human CD40 antibody 5C11 and β-glucan could be a promising therapeutic strategy for cancer patients.
    Journal
    |
    CD8 (cluster of differentiation 8) • CD86 (CD86 Molecule)
    6ms
    Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers (clinicaltrials.gov)
    P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Enrolling by invitation --> Active, not recruiting
    Enrollment closed
    |
    FOLR1 ( Folate receptor alpha )
    |
    pegylated liposomal doxorubicin • Elahere (mirvetuximab soravtansine-gynx) • SL-172154
    6ms
    Reversible Chemical Modification of Antibody Effector Function Mitigates Unwanted Systemic Immune Activation. (PubMed, Bioconjug Chem)
    The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion.
    Journal • IO biomarker
    |
    CD40 (CD40 Molecule)
    |
    cifurtilimab (SEA-CD40)
    6ms
    Next generation CD40 agonists for cancer immunotherapy. (PubMed, Expert Opin Biol Ther)
    Enhancing efficacy is the most important driver for this development, and approaches that maximize the ability of CD40 to both remodel the tumor microenvironment and boost the anti-tumor T cell response provide great opportunities to benefit cancer patients. Enhanced understanding of the role of different CD40 expressing immune cells in the tumor microenvironment may facilitate more efficient clinical development of these compounds.
    Review • Journal
    |
    CD40 (CD40 Molecule)
    |
    CD40 expression
    6ms
    Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, University of California, San Diego | Initiation date: Feb 2024 --> Jun 2024
    Trial initiation date • Metastases
    |
    mitazalimab (ADC-1013)
    6ms
    A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=150, Active, not recruiting, AbbVie | Trial completion date: Nov 2023 --> Sep 2024 | Trial primary completion date: Nov 2023 --> Sep 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 negative • PD-L1 negative
    |
    carboplatin • albumin-bound paclitaxel • budigalimab (ABBV-181) • giloralimab (ABBV-927) • revdofilimab (ABBV-368)
    6ms
    Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment (clinicaltrials.gov)
    P1, N=55, Recruiting, Memorial Sloan Kettering Cancer Center | N=25 --> 55 | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
    Enrollment change • Trial completion date • Trial primary completion date
    6ms
    Study to Evaluate Adverse Events and Change in Disease Activity When Intravenous (IV) Infusion of ABBV-927 is Administered in Combination With IV Modified FOLFIRINOX (mFFX) With or Without IV Budigalimab Compared to mFFX in Adult Participants With Untreated Pancreatic Cancer Metastasis (clinicaltrials.gov)
    P1/2, N=40, Completed, AbbVie | Active, not recruiting --> Completed | Phase classification: P1b/2 --> P1/2
    Trial completion • Phase classification • Adverse events • Combination therapy • Metastases
    |
    5-fluorouracil • oxaliplatin • irinotecan • budigalimab (ABBV-181) • leucovorin calcium • giloralimab (ABBV-927)
    7ms
    OPTIMIZE-1: Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients (clinicaltrials.gov)
    P1/2, N=90, Recruiting, Alligator Bioscience AB | Active, not recruiting --> Recruiting | Phase classification: P1b/2 --> P1/2 | Trial primary completion date: Feb 2024 --> Feb 2025
    Enrollment open • Phase classification • Trial primary completion date • Combination therapy • Metastases
    |
    5-fluorouracil • irinotecan • mitazalimab (ADC-1013)
    7ms
    Study of LVGN7409 (CD40 Agonist Antibody) in Locally Advanced, Metastatic or Recurrent/Refractory Malignancy (clinicaltrials.gov)
    P1, N=33, Completed, Lyvgen Biopharma Holdings Limited | Terminated --> Completed
    Trial completion • Tumor mutational burden • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • CD40 (CD40 Molecule)
    |
    MSI-H/dMMR
    |
    dalnicastobart (LVGN7409)
    7ms
    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
    7ms
    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)
    7ms
    Phase I Study of APX005M in Pediatric CNS Tumors (clinicaltrials.gov)
    P1, N=32, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Mar 2024 --> Sep 2024
    Trial completion date
    |
    TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
    |
    sotigalimab (PYX-107)