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

NCT05909397 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: C48910022022-500545-24-00
• Study Type: interventional
• Target: 59
• Locations: 10 countries
• Sites: 29

Brief 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. 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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (4)

• 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).

• 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).

• 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.

Secondary Outcomes (12)

• SLI and Phase 3. Objective Response Rate

  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

  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

  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

  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)

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

Study Arms (2)

Arm A (Investigational Arm)

EXPERIMENTAL

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

Drug: Vepdegestrant (ARV-471/PF-07850327); Combination Product: Palbociclib

Arm B (Comparator Arm):

ACTIVE COMPARATOR

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.

Drug: Letrozole; Combination Product: Palbociclib

Interventions

Palbociclib COMBINATION_PRODUCT

Pharmaceutical form: Capsules. Route of Administration: Oral.

Also known as: IBRANCE®

Arm A (Investigational Arm)

Letrozole DRUG

Pharmaceutical form: Capsules. Route of Administration: Orally

Also known as: FEMARA®

Arm B (Comparator Arm):

Vepdegestrant (ARV-471/PF-07850327) DRUG

Pharmaceutical form: Tablets. Route of Administration: Oral

Also known as: Vepdegestrant

Arm A (Investigational Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (29)

BRCR Global

Plantation, Florida, 33322, United States

Location

BRCR Medical Center Inc

Plantation, Florida, 33322, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Cancer Research SA

Adelaide, South Australia, 5000, Australia

Location

Barwon Health

Geelong, Victoria, 3220, Australia

Location

Hospital Santa Rita de Cassia

Vitória, Espírito Santo, 29043-260, Brazil

Location

Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Centro de Pesquisa Clínica - Área Administrativa

Porto Alegre, Rio Grande do Sul, 90850-170, Brazil

Location

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, 90880-480, Brazil

Location

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, 100021, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 04032, Hungary

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Naples, Campania, 80131, Italy

Location

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

Meldola, Emilia-Romagna, 47014, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy, 20900, Italy

Location

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Nemocnica na okraji mesta n o

Partizánske, 95801, Slovakia

Location

Fakultna nemocnica s poliklinikou J.A. Reimana Presov

Prešov, 080 01, Slovakia

Location

Institut Català d'Oncologia (ICO) - Badalona

Badalona, Barcelona [barcelona], 08916, Spain

Location

Hospital Universitari Dexeus

Barcelona, Catalunya [cataluña], 08028, Spain

Location

Complejo Hospitalario de Jaén

Jaén, JAÉN, 23007, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, 29010, Spain

Location

Hospital Unviersitario Virgen Nieves

Granada, 18012, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Tumor Zentrum Aarau

Aarau, Canton of Aargau, 5000, Switzerland

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 18, 2023
• Study Start: August 9, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); CH (1); JP (3); IT (3); BR (4); HU (1); CN (4); SL (2); US (3); ES (6)