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    DRUG:

    Veppanu (vepdegestrant)

    i
    Other names: ARV-471, PF-07850327, ARV471, PF07850327, ARV 471, PF 07850327
    Company:
    Arvinas, Pfizer
    Drug class:
    Selective estrogen receptor α degrader
    Related drugs:
    24d
    Approval of First PROTAC Opens New Era for Targeted Protein Degradation. (PubMed, Cancer Discov)
    The May 1 approval of vepdegestrant, the first PROTAC drug to earn regulatory clearance, establishes targeted protein degradation as a clinically validated therapeutic modality. For patients with ESR1-mutant advanced breast cancer, it offers a new therapeutic option after standard hormone-based regimens have failed. And for the broader field, it is proof of concept for a pipeline of protein-destroying drugs that now numbers in the dozens.
    Journal
    |
    ER (Estrogen receptor)
    |
    ESR1 mutation
    |
    Veppanu (vepdegestrant)
    1m
    Overcoming Breast Cancer Resistance through Targeted Protein Degradation and Next Generation Chimeras. (PubMed, Pharmacol Res)
    Notably, the ERα degrader vepdegestrant (ARV-471) achieved positive Phase III results in the VERITAC-2 trial, demonstrating significant progression-free survival benefit in ESR1-mutant ER+/HER2- breast cancer, marking a milestone for PROTAC clinical translation...Emerging technologies such as lysosome-targeting chimeras (LYTAC) and next-generation E3 ligases expand the druggable target space. With over 30 PROTACs currently in clinical trials across oncology, this review provides a comprehensive analysis of PROTAC applications in breast cancer and outlines future directions for precision medicine.
    Review • Journal • PARP Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BRD4 (Bromodomain Containing 4)
    |
    HER-2 negative • ESR1 mutation
    |
    Veppanu (vepdegestrant)
    1m
    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: Apr 2026 --> Dec 2026 | Trial primary completion date: Apr 2026 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    TP53 mutation
    |
    Veppanu (vepdegestrant) • samuraciclib (CT7001)
    1m
    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 | N=219 --> 624
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    fulvestrant • Veppanu (vepdegestrant)
    2ms
    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, Completed, Arvinas Estrogen Receptor, Inc. | Active, not recruiting --> Completed
    Trial completion
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • Veppanu (vepdegestrant)
    2ms
    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
    |
    Veppanu (vepdegestrant)
    2ms
    C4551001: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P2, N=320, Recruiting, Pfizer | Phase classification: P1 --> P2 | Trial primary completion date: Feb 2028 --> Jul 2029
    Phase classification • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
    |
    ER positive • HER-2 negative • HER-2 negative + ER positive
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • Veppanu (vepdegestrant) • atirmociclib (PF-07220060) • prifetrastat (PF-07248144)
    3ms
    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
    |
    Veppanu (vepdegestrant)
    3ms
    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
    |
    Veppanu (vepdegestrant) • atirmociclib (PF-07220060)
    4ms
    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)
    |
    Veppanu (vepdegestrant)
    4ms
    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) • Veppanu (vepdegestrant)
    5ms
    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
    |
    Veppanu (vepdegestrant) • itraconazole