A Study of Vepdegestrant (ARV-471, PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer

Last updated: May 15, 2025
Sponsor: Pfizer
Overall Status: Active - Not Recruiting

Phase

3

Condition

Cancer

Breast Cancer

Treatment

Palbociclib

Letrozole

ARV-471 (PF-07850327)

Clinical Study ID

NCT05909397
C4891002
2022-500545-24-00
  • Ages > 18
  • All Genders

Study Summary

The purpose of this study is to understand the safety and effects of the study medicine ARV-471 (PF-07850327) given together with palbociclib in advanced breast cancer. In particular, the study will compare the combination of ARV-471 plus palbociclib to standard of care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are medicines already used for treatment of breast cancer. ARV-471 is a new medicine under study.

This study is seeking participants who have breast cancer that:

  • Have a locally advanced or metastatic disease and cannot be fully cured by surgery or radiation therapy. A metastatic disease is when disease has spread to other parts of the body.

  • Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor positive disease.

  • Have not received any prior medicine for advanced disease. Example medications include tamoxifen or letrozole or exemestane.

The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial. During SLI, two dose levels of palbociclib in combination with ARV-471 will be explored in parallel. Assignment to the palbociclib dose is by chance. Half of the participant will receive one dose and the other half another palbociclib dose. The purpose of SLI is to determine the recommended Phase 3 dose of palbociclib to be administered in combination with ARV-471.

In the Phase 3, half of the participants will take ARV-471 plus palbociclib while the other half will take letrozole plus palbociclib. In both SLI and Phase 3, participants will take the study medicines by mouth, with food, once a day. Participants will take the study medicines until breast cancer increase in size or side effects become too severe. Side effects refer to unwanted reactions to medications. Participants will visit the study clinic about once every 4 weeks.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Adult participants with loco-regional recurrent or metastatic disease not amenableto curative treatment

  • Confirmed diagnosis of ER+/HER2- breast cancer

  • No prior systemic treatment for loco-regional recurrent or metastatic disease

  • Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2

  • Phase 3 only: Participants should be willing to provide blood and tumor tissue

Exclusion

Exclusion Criteria:

  • Disease recurrence while on, or within 12 months of completion of adjuvant endocrinetherapy

  • Prior treatment with cyclin dependent kinase 4/6 inhibitors (CDK4/6i), fulvestrant,elacestrant and other investigational drugs including novel endocrine therapies, anyselective estrogen receptor degraders (SERDs), covalent antagonists (SERCAs) andcomplete ER antagonists (CERANs).

  • Inadequate liver, kidney and bone marrow function

  • Impaired cardiovascular function or clinically significant cardiovascular diseases

  • Refractory nausea and vomiting, inability to swallow capsules and tablets whole,chronic gastrointestinal diseases, significant gastric (total or partial) or bowelresection that would preclude adequate absorption of study interventions.

  • Current use or anticipated need for food, herbal supplements or drugs that are knownstrong CYP3A4 inhibitors or inducers.

Study Design

Total Participants: 59
Treatment Group(s): 3
Primary Treatment: Palbociclib
Phase: 3
Study Start date:
August 09, 2023
Estimated Completion Date:
December 30, 2026

Study Description

The purpose of this study is to demonstrate that ARV-471 in combination with palbociclib provides superior clinical benefit compared to letrozole in combination with palbociclib in participants with ER(+)/HER2(-) aBC who have not received any prior systemic anti-cancer therapies for their locoregionally advanced or metastatic disease. The study will have a Study Lead-in (SLI) and a Phase 3. In the SLI, 50 participants (approximately 25 each arm) will be randomly assigned on a 1:1 basis to one of the two dose levels (DLs). In the randomized Phase 3, approximately 1130 eligible participants (approximately 565 each arm) will be randomized in a 1:1 ratio to the Experimental Arm (ie, ARV-471 plus palbociclib at RP3D determined in the SLI) or Control Arm (ie, letrozole plus palbociclib at the registered doses). Randomization will be stratified by menopausal status at study entry, visceral disease and de novo metastatic disease.

Connect with a study center

  • Cancer Research SA

    Adelaide, South Australia 5000
    Australia

    Site Not Available

  • Cabrini Hospital -Brighton

    Brighton, Victoria 3186
    Australia

    Site Not Available

  • Barwon Health

    Geelong, Victoria 3220
    Australia

    Site Not Available

  • Cabrini Hospital - Malvern

    Malvern, Victoria 3144
    Australia

    Site Not Available

  • Hospital Santa Rita de Cassia

    Vitoria, Espírito Santo 29043-260
    Brazil

    Site Not Available

  • Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa

    Porto Alegre, RIO Grande DO SUL 90110-270
    Brazil

    Site Not Available

  • Centro de Pesquisa Clínica - Área Administrativa

    Porto Alegre, RIO Grande DO SUL 90850-170
    Brazil

    Site Not Available

  • Hospital Mae de Deus

    Porto Alegre, RIO Grande DO SUL 90880-480
    Brazil

    Site Not Available

  • A. C. Camargo Cancer Center

    SP, SÃO Paulo 01509-010
    Brazil

    Site Not Available

  • Cancer Hospital Chinese Academy of Medical Science

    Beijing, Beijing 100021
    China

    Site Not Available

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong 510060
    China

    Site Not Available

  • Hubei Cancer Hospital

    Wuhan, Hubei 430079
    China

    Site Not Available

  • The First Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, Shaanxi 710061
    China

    Site Not Available

  • Sir Run Run Shaw Hospital of Zhejiang University School of Medicine

    Hangzhou, Zhejiang 310016
    China

    Site Not Available

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, 04032
    Hungary

    Site Not Available

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale

    Napoli, Campania 80131
    Italy

    Site Not Available

  • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

    Meldola, Emilia-romagna 47014
    Italy

    Site Not Available

  • Fondazione IRCCS San Gerardo dei Tintori

    Monza, Lombardia 20900
    Italy

    Site Not Available

  • Aichi Cancer Center Hospital

    Nagoya, Aichi 464-8681
    Japan

    Site Not Available

  • National Cancer Center Hospital East

    Kashiwa, Chiba 277-8577
    Japan

    Site Not Available

  • National Cancer Center Hospital

    Chuo-ku, Tokyo 104-0045
    Japan

    Site Not Available

  • Nemocnica na okraji mesta n o

    Partizanske, 95801
    Slovakia

    Site Not Available

  • Fakultna nemocnica s poliklinikou J.A. Reimana Presov

    Presov, 080 01
    Slovakia

    Site Not Available

  • Institut Català d'Oncologia (ICO) - Badalona

    Badalona, Barcelona [barcelona] 08916
    Spain

    Site Not Available

  • Hospital Universitari Dexeus

    Barcelona, Catalunya [cataluña] 08028
    Spain

    Site Not Available

  • Complejo Hospitalario de Jaén

    Jaen, Jaén 23007
    Spain

    Site Not Available

  • Hospital Universitario Virgen de la Victoria

    Malaga, Málaga 29010
    Spain

    Site Not Available

  • Hospital Unviersitario Virgen Nieves

    Granada, 18012
    Spain

    Site Not Available

  • Hospital Clinico San Carlos

    Madrid, 28040
    Spain

    Site Not Available

  • Tumor Zentrum Aarau

    Aarau, Aargau 5000
    Switzerland

    Site Not Available

  • CHUV (centre hospitalier universitaire vaudois)

    Lausanne, Vaud 1011
    Switzerland

    Site Not Available

  • Lakeland Regional Cancer Center

    Lakeland, Florida 33805
    United States

    Site Not Available

  • Radiology and Imaging Specialists

    Lakeland, Florida 33805
    United States

    Site Not Available

  • Mid Florida Hematology and Oncology Center

    Orange City, Florida 32763
    United States

    Site Not Available

  • BRCR Medical Center Inc

    Plantation, Florida 33322
    United States

    Site Not Available

  • POM MRI & Radiology Center of Plantation

    Plantation, Florida 33313
    United States

    Site Not Available

  • University of Michigan

    Ann Arbor, Michigan 48109
    United States

    Site Not Available

  • Mercy Clinic Oncology and Hematology

    Ballwin, Missouri 63011
    United States

    Site Not Available

  • Mercy Research - David C. Pratt Cancer Center

    Saint Louis, Missouri 63141
    United States

    Site Not Available

  • SCRI Oncology Partners

    Nashville, Tennessee 37203
    United States

    Site Not Available

  • Sarah Cannon Research Institute

    Nashville, Tennessee 37203
    United States

    Site Not Available

  • Virginia Oncology Associates

    Norfolk, Virginia 23502
    United States

    Site Not Available

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