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    DRUG:

    vepdegestrant (ARV-471)

    i
    Company:
    Arvinas, Pfizer
    Drug class:
    Ubiquitin pathway modulator, Estrogen receptor alpha degrader
    Related drugs:
    12d
    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)
    2ms
    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)
    2ms
    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
    |
    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)
    2ms
    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)
    4ms
    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
    |
    ER (Estrogen receptor)
    |
    ER positive • ER Y537S
    |
    vepdegestrant (ARV-471)
    4ms
    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)
    4ms
    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)
    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=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
    |
    Verzenio (abemaciclib) • vepdegestrant (ARV-471)
    4ms
    A Study to Learn About the Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (BC) (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, Pfizer | Trial completion date: Sep 2024 --> Mar 2025
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    vepdegestrant (ARV-471)
    5ms
    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, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    6ms
    A Study to Learn How Various Tablets of the Study Medicine Vepdegestrant Are Taken up Into the Blood of Healthy Adults (clinicaltrials.gov)
    P1, N=52, Completed, Pfizer | Active, not recruiting --> Completed
    Trial completion
    |
    vepdegestrant (ARV-471)
    6ms
    A Study to Learn About the Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (BC) (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, Pfizer | Trial completion date: Mar 2024 --> Sep 2024
    Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    vepdegestrant (ARV-471)
    6ms
    Stability Evaluation and Pharmacokinetic Profiling of Vepdegestrant in Rodents Using Liquid Chromatography-Tandem Mass Spectrometry. (PubMed, Molecules)
    We developed and validated a sensitive and rapid liquid chromatography-tandem mass spectrometry method to quantify vepdegestrant in rodent plasma using bavdegalutamide (formerly ARV-110) as an internal standard. In liver microsomes, vepdegestrant exhibited moderate stability in rats but was stable in mice, dogs, and humans. These findings enhance the understanding of pharmacokinetic properties of vepdegestrant supporting further development of PROTAC drugs.
    PK/PD data • Preclinical • Journal
    |
    ER (Estrogen receptor)
    |
    ER positive
    |
    bavdegalutamide (ARV-110) • vepdegestrant (ARV-471)
    7ms
    TACTIVE-N: A Trial Using ARV-471 or Anastrozole in Post-Menopausal Women With Breast Cancer Prior to Surgery (clinicaltrials.gov)
    P2, N=152, Completed, Arvinas Inc. | Active, not recruiting --> Completed
    Trial completion • Surgery
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    anastrozole • vepdegestrant (ARV-471)
    8ms
    VERITAC-2: A Study to Learn About a New Medicine Called ARV-471 (PF-07850327) in People Who Have Advanced Metastatic Breast Cancer. (clinicaltrials.gov)
    P3, N=560, Recruiting, Pfizer | Trial primary completion date: Aug 2024 --> Nov 2024
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    fulvestrant • vepdegestrant (ARV-471)
    8ms
    VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER degrader, versus fulvestrant in ER+/HER2- advanced breast cancer. (PubMed, Future Oncol)
    Progression-free survival by blinded independent central review (primary end point) will be assessed in the intention-to-treat population and ESR1 mutation-positive subpopulation. Secondary end points include overall survival, tumor response, safety, pharmacokinetics, patient-reported outcomes, and circulating tumor DNA biomarkers.Clinical trial registration: NCT05654623 (ClinicalTrials.gov).
    P3 data • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    fulvestrant • vepdegestrant (ARV-471)
    9ms
    A Study to Learn How Various Tablets of the Study Medicine Vepdegestrant Are Taken up Into the Blood of Healthy Adults (clinicaltrials.gov)
    P1, N=52, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    vepdegestrant (ARV-471)
    9ms
    VERITAC-3: A Study of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer (clinicaltrials.gov)
    P3, N=1180, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    Ibrance (palbociclib) • letrozole • vepdegestrant (ARV-471)
    10ms
    A Study to Learn If the Study Medicine Esomeprazole Changes How the Body Processes the Other Study Medicine Vepdegestrant (clinicaltrials.gov)
    P1, N=12, Completed, Pfizer | Recruiting --> Completed
    Trial completion
    |
    vepdegestrant (ARV-471)
    10ms
    Oral estrogen receptor PROTAC® vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4/6 or PI3K/mTOR pathway inhibitors in preclinical ER+ breast cancer models. (PubMed, Clin Cancer Res)
    Vepdegestrant achieved greater ER degradation in-vivo compared to fulvestrant, which correlated with improved tumor growth inhibition, suggesting vepdegestrant could be a more effective backbone ET for patients with ER+/HER2- breast cancer.
    Preclinical • Journal • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    Ibrance (palbociclib) • everolimus • Piqray (alpelisib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • vepdegestrant (ARV-471) • Itovebi (inavolisib)
    10ms
    C4891039: A Study to Learn If the Study Medicine Called Vepdegestrant Changes How the Body Processes the Other Study Medicine Called Midazolam (clinicaltrials.gov)
    P1, N=15, Completed, Pfizer | Recruiting --> Completed
    Trial completion
    |
    vepdegestrant (ARV-471) • midazolam hydrochloride
    11ms
    ARV-471-mBC-101: 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. | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Sep 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • vepdegestrant (ARV-471)
    11ms
    A Study to Learn How Various Tablets of the Study Medicine Vepdegestrant Are Taken up Into the Blood of Healthy Adults (clinicaltrials.gov)
    P1, N=48, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471)
    11ms
    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=67, Recruiting, Pfizer | Trial completion date: Aug 2027 --> Jan 2027 | Trial primary completion date: Feb 2027 --> Jul 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    12ms
    A Study to Learn How Various Tablets of the Study Medicine Vepdegestrant Are Taken up Into the Blood of Healthy Adults (clinicaltrials.gov)
    P1, N=48, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    12ms
    C4891039: A Study to Learn If the Study Medicine Called Vepdegestrant Changes How the Body Processes the Other Study Medicine Called Midazolam (clinicaltrials.gov)
    P1, N=16, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471) • midazolam hydrochloride
    12ms
    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=67, Recruiting, Pfizer | Trial completion date: Feb 2027 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Feb 2027
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    12ms
    A Study to Learn If the Study Medicine Esomeprazole Changes How the Body Processes the Other Study Medicine Vepdegestrant (clinicaltrials.gov)
    P1, N=12, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471)
    1year
    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=47, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2 | N=35 --> 47 | Trial completion date: Oct 2027 --> Dec 2026 | Trial primary completion date: Apr 2026 --> Dec 2026
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Kisqali (ribociclib) • vepdegestrant (ARV-471)
    1year
    A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer. (clinicaltrials.gov)
    P1/2, N=65, Recruiting, Pfizer | Not yet recruiting --> Recruiting | Trial completion date: Nov 2026 --> Feb 2026 | Trial primary completion date: May 2026 --> Aug 2025
    Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    vepdegestrant (ARV-471) • atirmociclib (PF-07220060)
    1year
    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=67, Recruiting, Pfizer | Phase classification: P2 --> P1/2
    Phase classification • Combination therapy • Metastases
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    1year
    A Study to Learn If the Study Medicine Esomeprazole Changes How the Body Processes the Other Study Medicine Vepdegestrant (clinicaltrials.gov)
    P1, N=12, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    1year
    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=40, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jun 2027 --> Dec 2025
    Phase classification • Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Verzenio (abemaciclib) • vepdegestrant (ARV-471)
    1year
    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)
    P2, N=67, Recruiting, Pfizer
    New P2 trial • Combination therapy • Metastases
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    1year
    A Study to Learn If the Study Medicine Called Vepdegestrant Changes How the Body Processes the Other Study Medicine Called Midazolam (clinicaltrials.gov)
    P1, N=16, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471) • midazolam hydrochloride
    1year
    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)
    P2, N=67, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    1year
    Annual review of PROTAC degraders as anticancer agents in 2022. (PubMed, Eur J Med Chem)
    As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies...In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • BRD4 (Bromodomain Containing 4) • CDK9 (Cyclin Dependent Kinase 9)
    |
    KRAS mutation
    |
    vepdegestrant (ARV-471)
    1year
    TACTIVE-E: ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer (clinicaltrials.gov)
    P1, N=32, Active, not recruiting, Arvinas Estrogen Receptor, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b --> P1
    Enrollment closed • Phase classification • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    everolimus • vepdegestrant (ARV-471)
    1year
    TACTIVE-N: A Trial Using ARV-471 or Anastrozole in Post-Menopausal Women With Breast Cancer Prior to Surgery (clinicaltrials.gov)
    P2, N=152, Active, not recruiting, Arvinas Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Surgery
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    anastrozole • vepdegestrant (ARV-471)
    1year
    A Study to Learn About the Study Medicine (Called ARV-471) in People With ER+/HER2- Advanced BC in China (clinicaltrials.gov)
    P1, N=9, Active, not recruiting, Pfizer | Trial primary completion date: Nov 2023 --> Mar 2024
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative
    |
    vepdegestrant (ARV-471)
    1year
    PK: A Study to Understand the Effects of Carbamazepine on How Vepdegestrant is Processed in Healthy Participants (clinicaltrials.gov)
    P1, N=12, Completed, Pfizer | Active, not recruiting --> Completed
    Trial completion
    |
    vepdegestrant (ARV-471)
    1year
    A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer. (clinicaltrials.gov)
    P1/2, N=65, Not yet recruiting, Pfizer
    New P1/2 trial • Combination therapy • Metastases
    |
    vepdegestrant (ARV-471) • atirmociclib (PF-07220060)