^
    over1year
    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)
    |
    2141-V11
    over1year
    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
    |
    2141-V11 • D2C7-IT
    over1year
    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
    |
    2141-V11
    over1year
    A Study of 2141-V11 in Combination With Standard Treatments in People With Prostate Cancer (clinicaltrials.gov)
    P2, N=99, Recruiting, Memorial Sloan Kettering Cancer Center
    New P2 trial • Combination therapy • Metastases
    |
    2141-V11
    almost2years
    Phase 1 Trial of D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma (clinicaltrials.gov)
    P1, N=30, Recruiting, Annick Desjardins, MD | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial primary completion date • Combination therapy
    |
    2141-V11 • D2C7-IT
    almost2years
    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)
    |
    2141-V11 • CDX-1140 • cifurtilimab (SEA-CD40) • dalnicastobart (LVGN7409) • mitazalimab (ADC-1013) • selicrelumab (RG7876) • sotigalimab (PYX-107)
    2years
    Phase 1/1b trial of Fc-engineered Anti-CD40 Agonist Monoclonal Antibody (2141-V11) infused with D2C7-IT in enhancing disease by Convection-Enhanced Delivery (CED) for Recurrent Malignant Glioma (rMG) (SNO 2023)
    Eligibility includes adult patients with solitary supratentorial rMG (WHO grade 3/4); ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. The RP2D for intratumoral infusion of D2C7-IT+2141-V11 via CED is identified. The protocol was amended to evaluate the addition of cervical perilymphatic injections of 2141-V11 post CED of D2C7-IT+2141-V11.
    P1 data • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8)
    |
    EGFR mutation • EGFR wild-type
    |
    Avastin (bevacizumab) • 2141-V11 • D2C7-IT
    2years
    D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients (clinicaltrials.gov)
    P1/2, N=50, Recruiting, Darell Bigner | Not yet recruiting --> Recruiting
    Enrollment open
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    2141-V11 • D2C7-IT
    over2years
    IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer. (PubMed, Proc Natl Acad Sci U S A)
    Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Collectively, these data reveal an important role for IL-15 in mediating antitumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to develop combinations of these promising therapeutics for the treatment of patients with bladder cancer.
    Journal
    |
    CD8 (cluster of differentiation 8) • CD40 (CD40 Molecule) • IL15 (Interleukin 15)
    |
    2141-V11
    over2years
    D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients (clinicaltrials.gov)
    P1/2, N=50, Not yet recruiting, Darell Bigner | Initiation date: May 2023 --> Aug 2023
    Trial initiation date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    2141-V11 • D2C7-IT
    almost3years
    D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients (clinicaltrials.gov)
    P1/2, N=50, Not yet recruiting, Darell Bigner
    New P1/2 trial
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    2141-V11 • D2C7-IT