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    DRUG CLASS:

    GPNMB-targeted antibody-drug conjugate

    Related drugs:
    2ms
    Phase 1 Study of PF-08046033 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=250, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open • IO biomarker
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    PD-L1 (Programmed death ligand 1)
    2ms
    Phase 1 Study of PF-08046033 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=250, Not yet recruiting, Pfizer
    New P1 trial • IO biomarker
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    PD-L1 (Programmed death ligand 1)
    7ms
    GPNMB immunohistochemistry is a useful ancillary tool for the diagnosis of pulmonary lymphangioleiomyomatosis. (PubMed, Histopathology)
    Based on its 100% sensitivity and specificity, GPNMB appears to be a highly valuable immunohistochemical marker for the diagnosis of pulmonary LAM. Besides its diagnostic value, the membrane positivity of GPNMB on LAM cells may predict a response to glembatumumab vedotin, an antibody-drug conjugate targeting GPNMB.
    Journal
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    GPNMB (Glycoprotein Nmb)
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    glembatumumab vedotin (CDX-011)
    11ms
    First-in-Human Phase 1/2 Study of INCAGN01876, a Glucocorticoid-Induced Tumor Necrosis Factor Receptor Agonist, in Patients with Advanced or Metastatic Solid Tumors. (PubMed, Clin Cancer Res)
    INCAGN01876 was generally well tolerated; fatigue was the most frequent TRAE. INCAGN01876 elicited transient and variable Treg depletion and limited antitumor activity. Future studies will explore combinatorial approaches.
    P1/2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    TNFA (Tumor Necrosis Factor-Alpha)
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    Keytruda (pembrolizumab) • glembatumumab vedotin (CDX-011) • ragifilimab (INCAGN1876)
    2years
    Expression of Potential Antibody-Drug Conjugate Targets in Cervical Cancer. (PubMed, Cancers (Basel))
    Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.
    Journal
    |
    FOLR1 ( Folate receptor alpha ) • MSLN (Mesothelin) • CEACAM5 (CEA Cell Adhesion Molecule 5) • DLL3 (Delta Like Canonical Notch Ligand 3) • CD70 (CD70 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • GPNMB (Glycoprotein Nmb) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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    TROP2 expression • CD70 expression • SDC1 positive
    almost3years
    TACSTD2 (Trop-2) constitutes a promising antibody-drug conjugate target for patients with non-small cell lung cancer brain metastases (ESMO 2023)
    Further validation is warranted in terms of protein expression. Our results underscore the potential value of gene expression profiling to identify new targets and improve patient selection in the context of NSCLC-BM ADC therapy.
    Clinical
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • AXL (AXL Receptor Tyrosine Kinase) • MSLN (Mesothelin) • CD276 (CD276 Molecule) • CEACAM5 (CEA Cell Adhesion Molecule 5) • SLC34A2 (Solute carrier family 34 member 2) • ROR2 (Receptor Tyrosine Kinase Like Orphan Receptor 2) • PTK7 (Protein Tyrosine Kinase 7) • GPNMB (Glycoprotein Nmb) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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    HER-2 expression • TROP2 expression
    3years
    Glycoprotein-NMB (GPNMB) is a Potential Lymphangioleiomyomatosis (LAM) Therapeutic Target and Biomarker (ENDO 2023)
    Inhibition of mTORC1 with Sirolimus slows but does not stop LAM progression; therefore, there is a need for new LAM treatment options and biomarkers...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*
    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • GPNMB (Glycoprotein Nmb) • ADAM10 (ADAM Metallopeptidase Domain 10)
    |
    TSC1 mutation • TSC2 mutation
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    sirolimus
    3years
    Glycoprotein-NMB (GPNMB) is a Potential Lymphangioleiomyomatosis (LAM) Therapeutic Target and Biomarker (ENDO 2023)
    Inhibition of mTORC1 with Sirolimus slows but does not stop LAM progression; therefore, there is a need for new LAM treatment options and biomarkers...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*
    TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • GPNMB (Glycoprotein Nmb) • ADAM10 (ADAM Metallopeptidase Domain 10)
    |
    TSC1 mutation • TSC2 mutation
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    sirolimus
    3years
    Human Antibody V Domains Targeting GPNMB and VCAM-1 as Candidate Therapeutics for Cancers. (PubMed, Mol Pharm)
    Domain-based bispecific T-cell engagers (DbTE) based on these two antibodies combined with the anti-CD3ε OKT3 antibody exhibited potent killing against GPNMB and VCAM-1-positive cancer cells, respectively. Hence, these two domain antibodies are promising therapeutic candidates for cancers expressing GPNMB or VCAM-1.
    Journal • IO biomarker
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    GPNMB (Glycoprotein Nmb) • VCAM1 (Vascular Cell Adhesion Molecule 1)
    3years
    High-throughput and targeted drug screens identify pharmacological candidates against MiT-translocation renal cell carcinoma. (PubMed, J Exp Clin Cancer Res)
    The results of the high-throughput drug screen and validation studies in TFE3-RCC tumor-derived cell lines have provided in vitro and in vivo preclinical data supporting the efficacy of the PI3K/mTOR inhibitor NVP-BGT226, the transcription inhibitor Mithramycin A, and GPNMB-targeted antibody-drug conjugate CDX-011 as potential therapeutic options for treating advanced MiT-RCC. The findings presented here should provide the basis for designing future clinical trials for patients with MiT-driven RCC.
    Journal
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    TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • GPNMB (Glycoprotein Nmb) • MITF (Melanocyte Inducing Transcription Factor) • TFEB (Transcription Factor EB 2)
    |
    sirolimus • glembatumumab vedotin (CDX-011) • BGT226
    over3years
    ImmunoPET Imaging Identifies the Optimal Timepoint for Combination Therapy in Xenograft Models of Triple-Negative Breast Cancer. (PubMed, Cancers (Basel))
    (4) Dasatinib upregulated gpNMB expression in gpNMB-positive MDA-MB-468 xenografted tumors at 14 days post treatment initiation, which can be quantified by PET imaging with [Zr]Zr-DFO-CR011. Furthermore, combination therapy with dasatinib and CDX-011 appears to be a promising therapeutic strategy for TNBC and warrants further investigation.
    Preclinical • Journal • Combination therapy
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    GPNMB (Glycoprotein Nmb)
    |
    dasatinib • glembatumumab vedotin (CDX-011)