^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG CLASS:

    SEMA4D inhibitor

    Related drugs:
    4ms
    VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Head and Neck Cancer (clinicaltrials.gov)
    P1, N=50, Recruiting, Emory University | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Jun 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • pepinemab (VX15)
    7ms
    Trial of Immunotherapy With Avelumab and Pepinemab As Second Line For Patients With Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P1/2, N=48, Active, not recruiting, Vaccinex Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2
    Enrollment closed • Phase classification
    |
    Bavencio (avelumab) • pepinemab (VX15)
    10ms
    VX15/2503 in Combination with Ipilimumab or Nivolumab in Patients with Head and Neck Cancer (clinicaltrials.gov)
    P1, N=50, Recruiting, Emory University | Trial completion date: Jul 2025 --> Nov 2025 | Trial primary completion date: Jul 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • pepinemab (VX15)
    10ms
    Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine & Pepinemab /Trastuzumab in Patients w/ Metastatic HER2+ Breast Cancer (clinicaltrials.gov)
    P1, N=28, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • PGR positive • HER-2 positive + HER-2 overexpression
    |
    Herceptin (trastuzumab) • Trazimera (trastuzumab-qyyp) • pepinemab (VX15)
    11ms
    Biomarkers. (PubMed, Alzheimers Dement)
    Given the many physiological parallels between glial activation and inflammatory processes in HD and AD, prior results from the SIGNAL-HD trial suggest that preventing astrocyte activation and reducing brain inflammation with pepinemab treatment could be an attractive alternative or complement to anti-Aβ antibodies.
    Journal
    |
    FAP (Fibroblast activation protein, alpha) • GFAP (Glial Fibrillary Acidic Protein) • SEMA4D (Semaphorin 4D)
    |
    pepinemab (VX15)
    11ms
    KEYNOTE B84: Pepinemab in Combination With Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov)
    P1/2, N=49, Completed, Vaccinex Inc. | Recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024 | Trial primary completion date: Dec 2024 --> Jul 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    Keytruda (pembrolizumab) • pepinemab (VX15)
    1year
    Pepinemab a semaphorin 4D blockade antibody in combination with immune checkpoint therapies induces mature lymphoid aggregates correlating with clinical outcomes (SITC 2024)
    The KEYNOTE-B84 study (NCT04815720) evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC. Biomarker studies conducted in patients with surgically resectable metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) received neoadjuvant treatment with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone...Increased density and maturity of lymphoid aggregates correlated with disease control and longer progression-free survival (PFS). Conclusions Pepinemab, a Semaphorin 4D (SEMA4D) blocking antibody, in combination with ICB converts 'Cold' tumors to 'Hot' by inducing organized lymphoid aggregates.
    Clinical • Clinical data • Combination therapy • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • SEMA4D (Semaphorin 4D)
    |
    PD-L1 underexpression • PD-L1 negative • PD-L1-L • CXCR5 expression
    |
    Sema4 Signal®
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • pepinemab (VX15)
    1year
    Inhibition of Semaphorin 4D induces lymphoid aggregates, correlating with clinical outcomes when combined with immune checkpoint therapy (CRI-ENCI-AACR ICIC 2024)
    Screening and on-treatment tumor biopsies were collected from several clinical trials: the KEYNOTE-B84 study (NCT04815720), that evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC, and biomarker neoadjuvant studies conducted in metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) patients with surgically resectable disease treated with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone. When SEMA4D is blocked from binding to its receptors, suppression is reduced, leading to increased penetration and organization of antigen presenting cells (APC) and lymphoid cells in the tumor microenvironment. It is expected that this would facilitate interaction and communication among these cell populations, accounting for improved immune responses in otherwise "cold" tumors.
    Clinical data • Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • SEMA4D (Semaphorin 4D)
    |
    PD-L1 underexpression • PD-L1-L • CXCR5 expression
    |
    Sema4 Signal®
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • pepinemab (VX15)
    over1year
    Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine & Pepinemab /Trastuzumab in Patients w/ Metastatic HER2+ Breast Cancer (clinicaltrials.gov)
    P1, N=28, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Jul 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CD4 (CD4 Molecule)
    |
    Herceptin (trastuzumab) • Trazimera (trastuzumab-qyyp) • pepinemab (VX15)
    over1year
    SIGNAL-AD: SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD) (clinicaltrials.gov)
    P1/2, N=50, Completed, Vaccinex Inc. | Active, not recruiting --> Completed | Trial primary completion date: Jun 2023 --> Jun 2024
    Trial completion • Trial primary completion date
    |
    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • CHI3L1 (Chitinase 3-like 1) • TGFB1 (Transforming Growth Factor Beta 1) • NEFL (Neurofilament Light Chain) • SEMA4D (Semaphorin 4D)
    |
    pepinemab (VX15)
    over1year
    Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors (clinicaltrials.gov)
    P1/2, N=26, Completed, Children's Oncology Group | Active, not recruiting --> Completed
    Trial completion
    |
    pepinemab (VX15)
    over1year
    Correlative and spatial biomarker analysis of a phase 1/2b study to evaluate pepinemab in combination with pembrolizumab for first-line treatment of patients with recurrent or metastatic head and neck cancer. (ASCO 2024)
    P1/2 | "Results suggest that combination therapy induced formation of highly organized lymphoid aggregates in HNSCC tumors, with a high density of activated B cells, DC and T cells. Together with similar observations indicating that combination immunotherapy with pepinemab induces mature lymphoid structures in tumors of patients with metastatic melanoma, provides evidence of treatment-induced biologic activity corresponding with disease control and suggests a novel and independent mechanism of pepinemab to enhance immune interactions and ICI activity. Clinical trial information: NCT04815720."
    Clinical • Combination therapy
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD14 (CD14 Molecule) • CD68 (CD68 Molecule) • ITGAX (Integrin Subunit Alpha X) • SEMA4D (Semaphorin 4D)
    |
    Keytruda (pembrolizumab) • pepinemab (VX15)