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

    vepdegestrant (ARV-471)

    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:
    1d
    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
    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, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    3ms
    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)
    4ms
    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)
    4ms
    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)
    4ms
    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)
    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: 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)
    5ms
    Effect of vepdegestrant, a PROTAC oestrogen receptor degrader, on dabigatran and rosuvastatin pharmacokinetics in healthy participants. (PubMed, Br J Clin Pharmacol)
    Coadministration with vepdegestrant doubled dabigatran exposure and resulted in a minor increase (11%) in rosuvastatin exposure in humans.
    PK/PD data • Journal
    |
    ER (Estrogen receptor)
    |
    vepdegestrant (ARV-471)
    5ms
    C4551001: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=320, Recruiting, Pfizer | Trial completion date: Jan 2028 --> Sep 2029
    Trial 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 • vepdegestrant (ARV-471) • atirmociclib (PF-07220060) • prifetrastat (PF-07248144)
    6ms
    TACTIVE-U Sub-Study B: 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 B) (clinicaltrials.gov)
    P1/2, N=20, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=47 --> 20
    Enrollment closed • Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Kisqali (ribociclib) • vepdegestrant (ARV-471)
    6ms
    Advancing Predictions of Oral Drug Absorption, CYP3A4 Induction, and Transporter-Mediated Interactions Using a Human Primary Intestinal 3D Model (EpiIntestinal™). (PubMed, Clin Pharmacol Ther)
    However, PBPK modeling, using EpiIntestinal™ permeability data, accurately predicted the clinical maximum plasma concentration (Cmax) of the P-gp substrates digoxin and dabigatran etexilate, unlike the significant underpredictions from Caco-2 data...Combining induction parameters of rifampicin from EpiIntestinal™ with those from the TruVivo (human hepatic model) into PBPK modeling accurately captured DDI effects on midazolam, a sensitive CYP3A4/5 substrate. Additionally, the model accurately predicted clinical outcomes of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) mediated DDIs for ARV-471. These data underscore the potential of EpiIntestinal™ in predicting human Fa and Fg, and in quantitatively assessing CYP3A4 induction and transporter-based DDIs.
    Journal
    |
    CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    vepdegestrant (ARV-471) • midazolam hydrochloride • rifampicin