Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast Cancer

NCT ID: NCT05909397

Last Updated: 2026-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-09

Study Completion Date

2026-12-30

Brief Summary

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

In the Phase 3, half of the participants will take vepdegestrant 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.

Detailed Description

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The purpose of this study is to demonstrate that vepdegestrant (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, vepdegestrant 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.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (Investigational Arm)

Participants will receive:

* Vepdegestrant, orally, once daily, continuously, in a 28-day cycle, plus
* Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle

Group Type EXPERIMENTAL

Vepdegestrant (ARV-471/PF-07850327)

Intervention Type DRUG

Pharmaceutical form: Tablets. Route of Administration: Oral

Palbociclib

Intervention Type COMBINATION_PRODUCT

Pharmaceutical form: Capsules. Route of Administration: Oral.

Arm B (Comparator Arm):

Participants will receive:

* Letrozole, orally, once daily, continuously, in a 28-day cycle, plus
* Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.

Group Type ACTIVE_COMPARATOR

Letrozole

Intervention Type DRUG

Pharmaceutical form: Capsules. Route of Administration: Orally

Palbociclib

Intervention Type COMBINATION_PRODUCT

Pharmaceutical form: Capsules. Route of Administration: Oral.

Interventions

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Vepdegestrant (ARV-471/PF-07850327)

Pharmaceutical form: Tablets. Route of Administration: Oral

Intervention Type DRUG

Palbociclib

Pharmaceutical form: Capsules. Route of Administration: Oral.

Intervention Type COMBINATION_PRODUCT

Letrozole

Pharmaceutical form: Capsules. Route of Administration: Orally

Intervention Type DRUG

Palbociclib

Pharmaceutical form: Capsules. Route of Administration: Oral.

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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Vepdegestrant IBRANCE® FEMARA® IBRANCE®

Eligibility Criteria

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Inclusion Criteria

* Adult participants with loco-regional recurrent or metastatic disease not amenable to 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 Criteria

* Disease recurrence while on, or within 12 months of completion of adjuvant endocrine therapy
* Prior treatment with cyclin dependent kinase 4/6 inhibitors (CDK4/6i), vepdegestrant, fulvestrant, elacestrant and other investigational drugs including novel endocrine therapies, any selective estrogen receptor degraders (SERDs), covalent antagonists (SERCAs) and complete 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 bowel resection that would preclude adequate absorption of study interventions.
* Current use or anticipated need for food, herbal supplements or drugs that are known strong CYP3A4 inhibitors or inducers.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arvinas Estrogen Receptor, Inc.

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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BRCR Global

Plantation, Florida, United States

Site Status

BRCR Medical Center Inc

Plantation, Florida, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Cancer Research SA

Adelaide, South Australia, Australia

Site Status

Barwon Health

Geelong, Victoria, Australia

Site Status

Hospital Santa Rita de Cassia

Vitória, Espírito Santo, Brazil

Site Status

Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Centro de Pesquisa Clínica - Área Administrativa

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, China

Site Status

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status

Hubei Cancer Hospital

Wuhan, Hubei, China

Site Status

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Site Status

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, Campania, Italy

Site Status

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

Meldola, Emilia-Romagna, Italy

Site Status

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy, Italy

Site Status

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status

Nemocnica na okraji mesta n o

Partizánske, , Slovakia

Site Status

Fakultna nemocnica s poliklinikou J.A. Reimana Presov

Prešov, , Slovakia

Site Status

Institut Català d'Oncologia (ICO) - Badalona

Badalona, Barcelona [barcelona], Spain

Site Status

Hospital Universitari Dexeus

Barcelona, Catalunya [cataluña], Spain

Site Status

Complejo Hospitalario de Jaén

Jaén, JAÉN, Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Site Status

Hospital Unviersitario Virgen Nieves

Granada, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Tumor Zentrum Aarau

Aarau, Canton of Aargau, Switzerland

Site Status

Countries

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United States Australia Brazil China Hungary Italy Japan Slovakia Spain Switzerland

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4891002

To obtain contact information for a study center near you, click here.

Other Identifiers

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2022-500545-24-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

C4891002

Identifier Type: -

Identifier Source: org_study_id

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