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    DRUG CLASS:

    Ubiquitin pathway modulator

    Related drugs:
    8ms
    A Study to Learn How a Tablet Compared With an IV Infusion of the Study Medicine Called Vepdegestrant is Taken up Into the Blood in Healthy Adults (clinicaltrials.gov)
    P1, N=10, Not yet recruiting, Pfizer
    New P1 trial
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    vepdegestrant (ARV-471)
    8ms
    Vepdegestrant for the treatment of HR+/HER2- breast cancer. (PubMed, Expert Opin Pharmacother)
    The results of the phase III VERITAC-2 study, comparing vepdegestrant with fulvestrant, are expected to be available in 2025, and will provide the first data on the true clinical significance of vepdegestrant. Several phase III studies of combinations with vepdegestrant including + atirimociclib (a cyclin-dependent kinase 4 inhibitor) have been or are planned to be conducted. The results of these may not only transform the treatment landscape for advanced HR+/HER2- breast cancer but may pave the way for PROTAC as a new class of anti-cancer drugs that may make previously undruggable targets druggable.
    Review • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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    HR positive • HER-2 negative • ESR1 mutation
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    fulvestrant • vepdegestrant (ARV-471)
    9ms
    C4891024: TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C) (clinicaltrials.gov)
    P1/2, N=11, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=67 --> 11 | Trial completion date: Jan 2027 --> Nov 2025 | Trial primary completion date: Jul 2026 --> Nov 2025
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    10ms
    A Study to Learn About the Study Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Advanced Breast Cancer in China (clinicaltrials.gov)
    P1, N=9, Completed, Pfizer | Active, not recruiting --> Completed
    Trial completion
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    vepdegestrant (ARV-471)
    10ms
    PROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia. (PubMed, Cancers (Basel))
    These findings suggest a new role of GSPT1 in regulating leukemic transcriptional networks and open a new therapeutic strategy to target leukemic fusion genes in pediatric AML patients.
    Journal
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    RUNX1 (RUNX Family Transcription Factor 1) • CRBN (Cereblon) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CDK6 (Cyclin-dependent kinase 6) • ERG (ETS Transcription Factor ERG) • FUS (FUS RNA Binding Protein) • GSPT1 (G1 To S Phase Transition 1)
    |
    eragidomide (CC-90009)
    11ms
    Discovery of a Potent and Selective GSPT1 Molecular Glue Degrader for the Treatment of Castration-Resistant Prostate Cancer. (PubMed, J Med Chem)
    Importantly, 7d exhibits superior efficacy compared to 1 (CC-90009) in degrading GSPT1 in 22Rv1 cells with a DC50 value of 19 nM...Mechanistically, via degradation of GSPT1, 7d downregulates CRPC-related oncogenes in 22Rv1 cells, including AR, AR-V7, PSA, and c-Myc. Thus, our work provides a novel GSPT1 selective degrader with potent effectiveness in targeting Myc-driven CRPC.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • CRBN (Cereblon) • GSPT1 (G1 To S Phase Transition 1)
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    AR splice variant 7
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    eragidomide (CC-90009)
    11ms
    Unleashing the Power of Covalent Drugs for Protein Degradation. (PubMed, Med Res Rev)
    Two prominent PROTACs, ARV-471 and ARV-110, are currently undergoing phase III and II clinical trials, respectively. The concept of covalent degradation has also been utilized in various new forms of degraders, including covalent molecule glue (MG), in-cell click-formed proteolysis targeting chimera (CLIPTAC), HaloPROTAC, lysosome-targeting chimera (LYTAC) and GlueTAC. This review focuses on recent advancements in covalent degraders beyond covalent PROTACs and examines obstacles and future directions pertinent to this field.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • KEAP1 (Kelch Like ECH Associated Protein 1) • BTK (Bruton Tyrosine Kinase) • DDB1 (Damage Specific DNA Binding Protein 1)
    |
    bavdegalutamide (ARV-110) • vepdegestrant (ARV-471)
    11ms
    C4891038: A Study to Learn How Different Tablets of the Study Medicine Vepdegestrant Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov)
    P1, N=12, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471)
    1year
    Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα). (PubMed, J Med Chem)
    ERD-12310A achieved a DC50 value of 47 pM and is 10 times more potent than ARV-471...Importantly, ERD-12310A achieved strong tumor growth inhibition in MCF-7 xenograft tumors harboring the clinically relevant ESR1Y537S mutation, which confers resistance to traditional antiestrogens. Our data position ERD-12310A as a promising candidate for further development as a potential therapy for ER+ breast cancer.
    Journal
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    ER (Estrogen receptor)
    |
    ER positive • ER Y537S
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    vepdegestrant (ARV-471)
    1year
    VERITAC-2: A Study to Learn About a New Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People Who Have Advanced Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=624, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    fulvestrant • vepdegestrant (ARV-471)
    1year
    Safety and pharmacokinetics of vepdegestrant in Japanese patients with ER+ advanced breast cancer: a phase 1 study. (PubMed, Int J Clin Oncol)
    Vepdegestrant 200 mg QD was well tolerated in Japanese patients with ER+/HER2- advanced breast cancer with no notable differences in pharmacokinetics from Western patients.
    P1 data • PK/PD data • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    vepdegestrant (ARV-471)
    1year
    TACTIVE-U Sub-Study A: TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A) (clinicaltrials.gov)
    P1/2, N=36, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Sep 2025 | Trial primary completion date: Dec 2025 --> Sep 2025
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
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    Verzenio (abemaciclib) • vepdegestrant (ARV-471)