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    DRUG CLASS:

    Estrogen receptor alpha degrader

    Related drugs:
    23d
    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)
    27d
    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)
    28d
    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)
    1m
    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)
    1m
    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)
    2ms
    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)
    3ms
    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)
    3ms
    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)
    3ms
    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)
    4ms
    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)
    5ms
    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)
    5ms
    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)
    5ms
    Discovery and prospects of new heterocyclic Isatin-hydrazide derivative with a novel role as estrogen receptor α degrader in breast cancer cells. (PubMed, Front Chem)
    Tamoxifen and fulvestrant represent standard therapy options in estrogen-mediated disease but have their own limitations. Isatin-based triple angiokinase inhibitor BIBF1120 (Nintedanib) and multikinase inhibitor Sunitinib (Sutent) have been approved by the FDA...Finally, molecular dynamics (MD) simulations indicated stable behavior of the protein-ligand complex between ERα and its ligand 5i. Overall, these results suggest that the new isatin derivative 5i holds promise as a new ERα degrader.
    Journal
    |
    ER (Estrogen receptor)
    |
    sunitinib • tamoxifen • fulvestrant • nintedanib
    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, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    vepdegestrant (ARV-471)
    7ms
    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)
    7ms
    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)
    7ms
    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)
    7ms
    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
    8ms
    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)
    8ms
    LINC00173 silence and estrone supply suppress ER+ breast cancer by estrogen receptor α degradation and LITAF activation. (PubMed, Cancer Sci)
    Distinct functional disparities between estrogen subtypes emerge, with estradiol synergistically promoting ER+ BC cell growth with LINC00173, while estrone (E1) facilitated LITAF-transcriptional activation. In terms of therapeutic significance, silencing LINC00173 alongside moderate addition of E1 heightened TNFα and induced apoptosis, effectively inhibiting ER+ BC progression.
    Journal
    |
    ER (Estrogen receptor) • TNFA (Tumor Necrosis Factor-Alpha) • LINC00173 (Long Intergenic Non-Protein Coding RNA 173)
    |
    ER positive
    8ms
    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)
    8ms
    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)
    8ms
    A Study of AC682 for the Treatment of Locally Advanced or Metastatic ER+ Breast Cancer (clinicaltrials.gov)
    P1, N=21, Terminated, Accutar Biotechnology Inc | N=30 --> 21 | Trial completion date: Dec 2024 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Apr 2024; Voluntarily terminate the study since the sponsor's development strategy was adjusted.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive
    |
    AC0682
    9ms
    A Study of AC682 for the Treatment of Locally Advanced or Metastatic ER+ Breast Cancer (clinicaltrials.gov)
    P1, N=30, Active, not recruiting, Accutar Biotechnology Inc | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive
    |
    AC0682
    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=48, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    9ms
    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
    9ms
    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)
    9ms
    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)
    9ms
    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)
    10ms
    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)
    10ms
    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)
    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, Not yet recruiting, Pfizer
    New P1 trial
    |
    vepdegestrant (ARV-471)
    10ms
    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)
    10ms
    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)
    10ms
    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
    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)
    P2, N=67, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Enrollment open
    |
    vepdegestrant (ARV-471) • samuraciclib (CT7001)
    11ms
    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)
    11ms
    A Study of AC682 In Chinese Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=6, Terminated, Accutar Biotechnology Inc | Trial completion date: Dec 2024 --> Sep 2023 | Active, not recruiting --> Terminated; Voluntarily terminate the study since the sponsor's development strategy was adjusted.
    Trial completion date • Trial termination • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive
    |
    AC0682
    11ms
    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)
    11ms
    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)
    11ms
    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)
    11ms
    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)