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    BIOMARKER:

    VTCN1 overexpression

    i
    Other names: VTCN1, V-Set Domain Containing T Cell Activation Inhibitor 1, B7-H4, B7H4, B7S1, V-Set Domain-Containing T-Cell Activation Inhibitor 1, Immune Costimulatory Protein B7-H4, B7 Superfamily Member 1, B7 Family Member, H4, B7 Homolog 4, FLJ22418, B7h.5, B7x, T Cell Costimulatory Molecule B7x, T-Cell Costimulatory Molecule B7x, Protein B7S1, PRO1291, VCTN1, B7X
    Entrez ID:
    79679
    Related biomarkers:
    Expression
    Others
    5ms
    Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance. (PubMed, Mod Pathol)
    Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.
    Journal
    |
    AR (Androgen receptor) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    VTCN1 underexpression • AR expression • VTCN1 overexpression
    6ms
    C4431001: A Study of PF-07260437 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=30, Terminated, Pfizer | Trial completion date: Jan 2024 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2024 --> Oct 2023; Pfizer has made an internal business decision to not continue further development of PF-07260437. This decision was not due to major safety concerns or requests from any regulatory authorities.
    Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    HER-2 negative • VTCN1 underexpression • VTCN1 overexpression
    |
    PF-07260437
    6ms
    A B7-H4 targeting antibody-drug conjugate shows anti-tumor activity in PARPi and platinum resistant cancers with B7-H4 expression. (PubMed, Clin Cancer Res)
    These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population.
    Journal • PARP Biomarker
    |
    VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    VTCN1 underexpression • VTCN1 overexpression
    7ms
    C4431001: A Study of PF-07260437 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=25, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=100 --> 25 | Trial completion date: Sep 2025 --> Jan 2024 | Trial primary completion date: Sep 2025 --> Jan 2024
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    HER-2 negative • VTCN1 underexpression • VTCN1 overexpression
    |
    PF-07260437
    11ms
    Ethacrynic acid suppresses B7-H4 expression involved in epithelial-mesenchymal transition of lung adenocarcinoma cells via inhibiting STAT3 pathway. (PubMed, Biochem Pharmacol)
    In summary, these results suggested that ECA inhibits B7-H4 expression via STAT3 inhibition, leading to SPC/TGF-β1-induced EMT. Therefore, ECA might be an immune oncological drug for B7-H4-positive cancer, especially lung cancer.
    Journal
    |
    VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    VTCN1 underexpression • VTCN1 overexpression • STAT3 expression • CD4 positive
    12ms
    XMT-1660: A phase 1b trial of a B7-H4 targeted antibody drug conjugate (ADC) in breast, endometrial, and ovarian cancers. (ASCO 2023)
    XMT-1660 is a B7-H4-directed Dolasynthen antibody drug conjugate designed with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with controlled bystander effect. NCT05377996. Clinical trial information: NCT05377996.
    P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    HER-2 negative • VTCN1 underexpression • VTCN1 overexpression
    |
    emiltatug ledadotin (XMT-1660) • GM.CD40L cell vaccine
    1year
    A B7-H4 targeting antibody-drug conjugate shows anti-tumor activity in PARPi and platinum resistant cancers with B7-H4 expression (AACR 2023)
    These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC.
    PARP Biomarker
    |
    VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    VTCN1 underexpression • VTCN1 overexpression
    1year
    C4431001: A Study of PF-07260437 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=100, Recruiting, Pfizer | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    HER-2 negative • VTCN1 underexpression • VTCN1 overexpression
    |
    PF-07260437
    over1year
    B7-H4 is a potential diagnostic and prognostic biomarker in colorectal cancer and correlates with the epithelial-mesenchymal transition. (PubMed, BMC Cancer)
    B7-H4 may represent a potential biomarker for the diagnosis and prognosis of CRC and enhance CRC invasion by promoting EMT.
    Journal
    |
    CDH1 (Cadherin 1) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • VIM (Vimentin)
    |
    VTCN1 underexpression • VTCN1 overexpression • CDH1 expression • VIM expression
    over1year
    XMT-1660: A Phase 1b trial of a B7-H4 targeted antibody drug conjugate (ADC) in breast, endometrial, and ovarian cancers (SABCS 2022)
    The trial is currently enrolling patients. NCT05377996
    P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1)
    |
    HER-2 negative • VTCN1 underexpression • VTCN1 overexpression
    |
    emiltatug ledadotin (XMT-1660)
    over1year
    Comprehensive analysis of the association between RAS mutation and immune checkpoint marker expression (ESMO 2022)
    VTCN1 is a co-inhibitory molecule which negatively regulates T-cell immune response and promotes immune escape. The association between genetic mutations in cancer cells and the immune status in the tumor microenvironment may suggest potential treatment with combination targeted therapy plus immunotherapy.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • RAS (Rat Sarcoma Virus) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • NOS2 (Nitric Oxide Synthase 2)
    |
    KRAS mutation • KRAS G12D • KRAS G12V • RAS mutation • RAS wild-type • NRAS G12D • VTCN1 underexpression • VTCN1 overexpression • HRAS G12C