Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast Cancer (VERITAC-3)

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:

• 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Combination product: Palbociclib; Drug: Letrozole; Drug: Vepdegestrant (ARV-471/PF-07850327)

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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research SA
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Barwon Health
• Brazil
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29043-260
      • Hospital Santa Rita de Cassia
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
      • Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa
    • Porto Alegre, Rio Grande do Sul, Brazil, 90880-480
      • Hospital Mae de Deus
    • Porto Alegre, Rio Grande do Sul, Brazil, 90850-170
      • Centro de Pesquisa Clínica - Área Administrativa
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Science
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun yat-sen University Cancer Center
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
• Hungary
  • Debrecen, Hungary, 04032
    • Debreceni Egyetem Klinikai Kozpont
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
  • Lombardy
    • Monza, Lombardy, Italy, 20900
      • Fondazione IRCCS San Gerardo dei Tintori
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Slovakia
  • Partizánske, Slovakia, 95801
    • Nemocnica na okraji mesta n o
  • Prešov, Slovakia, 080 01
    • Fakultna nemocnica s poliklinikou J.A. Reimana Presov
• Spain
  • Granada, Spain, 18012
    • Hospital Unviersitario Virgen Nieves
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Barcelona [barcelona]
    • Badalona, Barcelona [barcelona], Spain, 08916
      • Institut Català d'Oncologia (ICO) - Badalona
  • Catalunya [cataluña]
    • Barcelona, Catalunya [cataluña], Spain, 08028
      • Hospital Universitari Dexeus
  • JAÉN
    • Jaén, JAÉN, Spain, 23007
      • Complejo Hospitalario de Jaén
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
• Switzerland
  • Canton of Aargau
    • Aarau, Canton of Aargau, Switzerland, 5000
      • Tumor Zentrum Aarau
• United States
  • Florida
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center Inc
    • Plantation, Florida, United States, 33322
      • BRCR Global
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Combination product: Palbociclib; Pharmaceutical form: Capsules. Route of Administration: Oral.; Other Names: IBRANCE®; Drug: Letrozole; Pharmaceutical form: Capsules. Route of Administration: Orally; Other Names: FEMARA®
Experimental: 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	Combination product: Palbociclib; Pharmaceutical form: Capsules. Route of Administration: Oral.; Other Names: IBRANCE®; Drug: Vepdegestrant (ARV-471/PF-07850327); Pharmaceutical form: Tablets. Route of Administration: Oral; Other Names: Vepdegestrant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From randomization date up to Cycle 4 (each cycle is 28 days).
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.	From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.
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.	From randomization date up to Cycle 4 (each cycle is 28 days).
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.	From randomization date up to Cycle 4 (each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).
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.	From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).
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.	Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).
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.	From randomization date, every 3 months, to date of death (up to approximately 6 years)
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.	From baseline to date to end of treatment (up to approximately 4 years)
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.	From baseline to end of treatment (up to approximately 4 years)
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.	From baseline up to the end of treatment (up to approximately 4 years)
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.	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
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.	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.
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.	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.
Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)	Quantitative changes from baseline	From baseline to end of treatment (up to approximately 4 years)
SLI and Phase 3: Plasma concentrations of vepdegestrant and palbociclib	Plasma concentrations of vepdegestrant and palbociclib	From randomization date up to Cycle 5 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Arvinas Estrogen Receptor, Inc.
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; Metastatic breast cancer; Estrogen receptor positive; ER positive; Letrozole; Palbociclib; Breast neoplasm; HER2-negative; Breast tumor; ARV-471; Advanced cancer of the breast; Vepdegestrant; Advanced tumor of the breast
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nitriles; Triazoles; Letrozole; palbociclib
• Other Study ID Numbers: C4891002; 2022-500545-24-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No