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Breast CancerPhase 3VERITAC-3NCT05909397

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

A Phase 3 study testing Vepdegestrant (ARV-471/PF-07850327), Palbociclib and Letrozole in people with Breast Cancer, run by Pfizer at 29 sites in 10 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Vepdegestrant (ARV-471/PF-07850327), Palbociclib and Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
29 sitesin 10 countries
Study dates
9 Aug 2023to 30 Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

29 sites in 10 countries.

29 sites in 10 countries

Spain6 sites

  • Institut Català d'Oncologia (ICO) - Badalona

    Badalona, Barcelona [barcelona], 08916

  • Hospital Universitari Dexeus

    Barcelona, Catalunya [cataluña], 08028

  • Hospital Unviersitario Virgen Nieves

    Granada, 18012

  • Complejo Hospitalario de Jaén

    Jaén, JAÉN, 23007

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario Virgen de la Victoria

    Málaga, Málaga, 29010

Other trials in Spain

Brazil4 sites

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

    Porto Alegre, Rio Grande do Sul, 90110-270

  • Centro de Pesquisa Clínica - Área Administrativa

    Porto Alegre, Rio Grande do Sul, 90850-170

  • Hospital Mae de Deus

    Porto Alegre, Rio Grande do Sul, 90880-480

  • Hospital Santa Rita de Cassia

    Vitória, Espírito Santo, 29043-260

Other trials in Brazil

China4 sites

  • Cancer Hospital Chinese Academy of Medical Science

    Beijing, Beijing Municipality, 100021

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

  • Hubei Cancer Hospital

    Wuhan, Hubei, 430079

  • The First Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, Shaanxi, 710061

Other trials in China

United States3 sites

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • BRCR Global

    Plantation, Florida, 33322

  • BRCR Medical Center Inc

    Plantation, Florida, 33322

Other trials in United States

Italy3 sites

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

    Meldola, Emilia-Romagna, 47014

  • Fondazione IRCCS San Gerardo dei Tintori

    Monza, Lombardy, 20900

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale

    Naples, Campania, 80131

Other trials in Italy

Japan3 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Aichi Cancer Center Hospital

    Nagoya, Aichi-ken, 464-8681

Other trials in Japan

Australia2 sites

  • Cancer Research SA

    Adelaide, South Australia, 5000

  • Barwon Health

    Geelong, Victoria, 3220

Other trials in Australia

Slovakia2 sites

  • Nemocnica na okraji mesta n o

    Partizánske, 95801

  • Fakultna nemocnica s poliklinikou J.A. Reimana Presov

    Prešov, 080 01

Other trials in Slovakia

Hungary1 site

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, 04032

Other trials in Hungary

Switzerland1 site

  • Tumor Zentrum Aarau

    Aarau, Canton of Aargau, 5000

Other trials in Switzerland

About this study

Official title: A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY OF VEPDEGESTRANT (ARV-471/PF-07850327) PLUS PALBOCICLIB VERSUS LETROZOLE PLUS PALBOCICLIB FOR THE TREATMENT OF PARTICIPANTS WITH ESTROGEN RECEPTOR POSITIVE, HER2 NEGATIVE BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE (VERITAC-3)

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:

Read more
  • 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.

Read the detailed description

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
Breast Cancer
Being tested
Vepdegestrant (ARV-471/PF-07850327), Palbociclib, Letrozole
Keywords
Advanced tumor of the breast, Advanced cancer of the breast, Breast neoplasm, Breast tumor, Breast cancer, ER positive, Estrogen receptor positive, HER2-negative, Metastatic breast cancer, Palbociclib, Letrozole, ARV-471, Vepdegestrant
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vepdegestrant (ARV-471/PF-07850327)Drug

    Also called Vepdegestrant

    Pharmaceutical form: Tablets. Route of Administration: Oral

  • PalbociclibCombination product

    Also called IBRANCE®

    Pharmaceutical form: Capsules. Route of Administration: Oral.

  • LetrozoleDrug

    Also called FEMARA®

    Pharmaceutical form: Capsules. Route of Administration: Orally

  • PalbociclibCombination product

    Also called IBRANCE®

    Pharmaceutical form: Capsules. Route of Administration: Oral.

Study groups in NCT05909397
Study groupRoleWhat they receive
Arm A (Investigational Arm)ExperimentalParticipants 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
Receives: Drug: Vepdegestrant (ARV-471/PF-07850327); Combination Product: Palbociclib
Arm B (Comparator Arm):Active comparatorParticipants 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.
Receives: Drug: Letrozole; Combination Product: Palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Study Lead-in (SLI): Incidence of Grade 4 neutropenia

    It is defined as the number of participants with Grade 4 neutropenia AE (graded by NCI CTCAE v.5.0) with onset within the first 4 cycles divided by the number of participants.

    Measured: From randomization date up to Cycle 4 (each cycle is 28 days).

  2. SLI: Incidence of dose reduction

    It is defined as the number of participants reducing the dose of palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.

    Measured: From randomization date up to Cycle 4 (each cycle is 28 days).

  3. SLI: Incidence of drug discontinuation.

    It is defined as the number of participants discontinuing palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.

    Measured: From randomization date up to Cycle 4 (each cycle is 28 days).

  4. Phase 3: Progression-Free Survival

    Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or death due to any cause, whichever come first.

    Measured: From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.

Secondary outcomes (12)

  1. SLI and Phase 3. Objective Response Rate

    Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as best overall response determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1, from the date of randomization to the date of disease progression or death due to any cause, whichever occurs first.

    Measured: From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).

  2. SLI and Phase 3: Duration of Response

    Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1 or death due to any cause, whichever occurs first.

    Measured: From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).

  3. SLI and Phase 3: Clinical Benefit Rate

    Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR at any time or SD or non CR/non PD for at least 24 weeks determined by Investigators (SLI) or by BICR (Phase 3) as per RECIST version 1.1, from the date of randomization until disease progression or death due to any cause, whichever occurs first.

    Measured: Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).

  4. Phase 3: Overall Survival

    Overall survival is defined as the time interval from the date of randomization to the date of documented death, due to any cause.

    Measured: From randomization date, every 3 months, to date of death (up to approximately 6 years)

  5. SLI and Phase 3: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    It is defined as the number of participants with TEAEs and SAEs divided by the number of participants. AEs and SAEs will be graded according to NCI CTCAE V5.0.

    Measured: From baseline to date to end of treatment (up to approximately 4 years)

  6. SLI and Phase 3: Incidence of laboratory abnormalities

    It is defined as the number of participants with laboratory abnormalities divided by the number of participants. Laboratory abnormalities will be graded according to NCI CTCAE V5.0.

    Measured: From baseline to end of treatment (up to approximately 4 years)

  7. SLI and Phase 3: Incidence of Electrocardiogram (ECG) Abnormalities

    It is defined as the number of participants with ECG abnormalities divided by the number of participants. ECG abnormalities will be graded according to NCI CTCAE V5.0.

    Measured: From baseline up to the end of treatment (up to approximately 4 years)

  8. SLI and Phase 3: Plasma concentrations of vepdegestrant and palbociclib

    Plasma concentrations of vepdegestrant and palbociclib

    Measured: From randomization date up to Cycle 5 (each cycle is 28 days)

  9. Phase 3: Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)

    Change from baseline between treatment comparison in Quality of Life using the EQ-5D 5L questionnaire.

    Measured: From baseline, each cycle up to cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days

  10. Phase 3: Disease-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)

    Change from baseline between treatment comparison in Quality of Life using the EORTC QLQ-C30 questionnaire.

    Measured: From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.

  11. Phase 3: Disease- and treatment-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) questionnaire.

    Change from baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) questionnaire.

    Measured: From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.

  12. Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)

    Quantitative changes from baseline

    Measured: From baseline to end of treatment (up to approximately 4 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2023
  2. Study start9 Aug 2023
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05909397
Sponsor's protocol ID
C4891002
Other IDs
2022-500545-24-00
Acronym
VERITAC-3
Status last verified
Feb 2026
First submitted
25 May 2023
Last updated
10 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vepdegestrant (ARV-471/PF-07850327), Palbociclib and Letrozole in people with Breast Cancer, run by Pfizer at 29 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in Spain, Brazil, China, United States, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Study Lead-in (SLI): Incidence of Grade 4 neutropenia (time frame: From randomization date up to Cycle 4 (each cycle is 28 days).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05909397.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.

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