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    DRUG CLASS:

    Selective estrogen receptor α degrader

    Related drugs:
    5d
    A Study to Learn How the Body Processes the Study Medicine Called Vepdegestrant in People With Loss of Liver Function (clinicaltrials.gov)
    P1, N=24, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471)
    14d
    Insights Into Vepdegestrant (ARV-471): The First-in-Class Estrogen Receptor Proteolysis-Targeting Chimera Approaching Food and Drug Administration Approval for Breast Cancer. (PubMed, ChemMedChem)
    On June 6, 2025, Arvinas and Pfizer submitted a New Drug Application (NDA) for vepdegestrant to the U.S. Food and Drug Administration (FDA), representing an important step in the clinical translation of PROTAC technology. This review summarizes the design, synthesis, degradation mechanism, preclinical pharmacology, and clinical development of vepdegestrant and discusses the broader implications and future prospects of oral PROTAC-based ER degraders in breast cancer therapy.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ESR1 mutation • EGFR positive
    |
    vepdegestrant (ARV-471)
    1m
    TACTIVE-K: A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer. (clinicaltrials.gov)
    P1/2, N=71, Active, not recruiting, Pfizer | Trial completion date: Mar 2026 --> Sep 2026
    Trial completion date
    |
    vepdegestrant (ARV-471) • atirmociclib (PF-07220060)
    2ms
    Effect of carbamazepine on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader, in healthy adults. (PubMed, Br J Clin Pharmacol)
    Coadministration of multiple doses of carbamazepine 200 mg, a strong CYP3A4 inducer, with a single dose of vepdegestrant 200 mg resulted in a modest (36%) decrease in plasma vepdegestrant exposure. A single dose of vepdegestrant 200 mg was well tolerated in healthy adult participants.
    PK/PD data • Journal
    |
    ER (Estrogen receptor) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    vepdegestrant (ARV-471)
    2ms
    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=37, Active, not recruiting, Pfizer | Trial completion date: Mar 2026 --> Sep 2026 | Trial primary completion date: Mar 2026 --> Sep 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Verzenio (abemaciclib) • vepdegestrant (ARV-471)
    3ms
    The Effect of Itraconazole on the Pharmacokinetics of Vepdegestrant, a PROteolysis TArgeting Chimera Estrogen Receptor Degrader, in Healthy Adult Participants. (PubMed, Clin Ther)
    Coadministration of multiple doses of itraconazole, a strong CYP3A4 inhibitor, increased vepdegestrant exposure by 69%, suggesting the involvement of CYP3A4-mediated metabolism, albeit not predominantly, in vepdegestrant elimination.
    PK/PD data • Journal • First-in-human
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • EGFR positive
    |
    vepdegestrant (ARV-471) • itraconazole
    5ms
    A Study to Learn How the Body Processes the Study Medicine Called Vepdegestrant in People With Loss of Liver Function (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    5ms
    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 | Trial completion date: Nov 2025 --> Apr 2026 | Trial primary completion date: Nov 2025 --> Apr 2026
    Trial completion date • Trial primary completion date
    |
    TP53 mutation
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    6ms
    VERITAC: A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P1/2, N=217, Active, not recruiting, Arvinas Estrogen Receptor, Inc. | Trial completion date: Aug 2025 --> Nov 2025
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • vepdegestrant (ARV-471)
    6ms
    Proteolysis-Targeting Chimera (PROTAC): Current Applications and Future Directions. (PubMed, MedComm (2020))
    We evaluate clinical progression of breakthrough candidates such as ARV-110 for prostate cancer, ARV-471 for breast cancer, and BTK degraders, while discussing critical challenges including the "hook effect" and oral bioavailability limitations. This review provides essential foundations for rational target selection, molecular optimization, and clinical translation strategies. By integrating mechanistic insights with clinical realities, this analysis offers perspectives on PROTAC technology advancement and identifies opportunities for transforming treatment of complex diseases resistant to conventional therapies.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    KRAS mutation • KRAS G12C • KRAS G12 • STAT3 mutation
    |
    bavdegalutamide (ARV-110) • vepdegestrant (ARV-471)
    6ms
    TACTIVE-E: ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer (clinicaltrials.gov)
    P1, N=32, Completed, Arvinas Estrogen Receptor, Inc. | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Aug 2025
    Trial completion • Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    everolimus • vepdegestrant (ARV-471)
    7ms
    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=37, Active, not recruiting, Pfizer | Trial completion date: Sep 2025 --> Mar 2026 | Trial primary completion date: Sep 2025 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Verzenio (abemaciclib) • vepdegestrant (ARV-471)