A Study to Learn About the Study Medicine PF-07220060 Together With Letrozole Compared to Letrozole Alone in Women Post Menopause

AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER, PHASE 2 STUDY OF PF-07220060 PLUS LETROZOLE COMPARED TO LETROZOLE ALONE IN POSTMENOPAUSAL WOMEN 18 YEARS OR OLDER WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER IN THE NEOADJUVANT SETTING

The purpose of this study is to learn about the effects of the study medicine PF-07220060 plus letrozole, compared with the effects of taking letrozole alone without PF-07220060 for treatment of breast cancer.

This study is seeking for participants who are:

• women of age 18 years and older post menopause (either naturally or surgically).
• confirmed to have Hormone receptor (HR) positive, Human epidermal growth factor receptor 2 (HER2) negative breast cancer. HER2 negative describes cells that have a small amount or none of a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface.
• not been treated for their cancer before this study.

Participants will be randomly assigned (like flipping a coin) to receive the treatment (PF-07220060 plus letrozole) or letrozole alone. Both PF-07220060 and letrozole are taken by mouth. PF-07220060 will be taken twice a day for 14 days. Letrozole will be taken once a day for 14 days.

Participants will have a screening period for up to 28 days. If deemed fit, they will receive study treatment for 14 days, and then will have a follow-up visit about 28 days after their last dose.

All participants will have at least one biopsy during the study. Biopsy is the removal of cells or tissues for examining. All participants will have a biopsy on Day 14.

Additional assessments for safety including blood draws and interviews done by the site staff will be completed during the study.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: PF-07220060; Drug: letrozole

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Parkville, Victoria, Australia, 3052
      • Royal Melbourne Hospital
• Belgium
  • Bruxelles-capitale, Région de
    • Anderlecht, Bruxelles-capitale, Région de, Belgium, 1070
      • Institut Jules Bordet
  • Vlaams-brabant
    • Leuven, Vlaams-brabant, Belgium, 3000
      • UZ Leuven
• France
  • Ille-et-vilaine
    • Rennes, Ille-et-vilaine, France, 35042
      • Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer
  • Languedoc-roussillon
    • Montpellier, Languedoc-roussillon, France, 34070
      • Centre de Cancerologie du Grand Montpellier
  • Loire-atlantique
    • Saint-Herblain, Loire-atlantique, France, 44805
      • Institut de Cancérologie de l'Ouest
  • Pays de la Loire Region
    • Saint Priest En Jarez, Pays de la Loire Region, France, 42271
      • CHU de Saint-Etienne
  • Rhône
    • Pierre-Bénite, Rhône, France, 69310
      • Centre Hospitalier Lyon Sud
    • Saint-Genis-Laval, Rhône, France, 69230
      • HCL, Centre Hospitalier Lyon Sud
  • Val-de-marne
    • Villejuif, Val-de-marne, France, 94800
      • Gustave Roussy
• Germany
  • Saarland
    • Saarbrücken, Saarland, Germany, 66113
      • Caritasklinikum Saarbrücken St. Theresia
• Italy
  • Brindisi, Italy, 72100
    • Ospedale Antonio Perrino
  • Novara, Italy, 28100
    • Azienda Ospedaliero Universitaria Maggiore della Carità
  • 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
  • Tuscany
    • Livorno, Tuscany, Italy, 57124
      • Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno
• Poland
  • Greater Poland Voivodeship
    • Skórzewo, Greater Poland Voivodeship, Poland, 60-185
      • AIDPORT Sp. z o.o.
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-727
      • Pratia MCM Krakow
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
  • Podkarpackie Voivodeship
    • Przemyśl, Podkarpackie Voivodeship, Poland, 37-700
      • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Narodny Onkologicky Ustav
  • Nitra Region
    • Komárno, Nitra Region, Slovakia, 945 05
      • Nemocnica AGEL Komarno
• South Korea
  • Seoul-teukbyeolsi [seoul]
    • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03080
      • Seoul National University Hospital
• Spain
  • Granada, Spain, 18016
    • Hospital Universitario San Cecilio
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
  • Barcelona [barcelona]
    • Barcelona, Barcelona [barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
  • Catalunya [cataluña]
    • Barcelona, Catalunya [cataluña], Spain, 08041
      • Hospital De La Santa Creu I Sant Pau
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital Jerez de la Frontera
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28041
      • Hospital Universitario 12 de octubre
    • Madrid, Madrid, Comunidad de, Spain, 28009
      • Hospital General Universitario Gregorio Marañon
  • Murcia, Región de
    • El Palmar, Murcia, Región de, Spain, 30120
      • Hospital Clínico Universitario Virgen de la Arrixaca
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
• Sweden
  • Gävleborgs LÄN [se-21]
    • Gävle, Gävleborgs LÄN [se-21], Sweden, 80187
      • Sjukhuset I Gävle
  • Uppsala LÄN [se-03]
    • Uppsala, Uppsala LÄN [se-03], Sweden, 751 85
      • Akademiska Sjukhuset
• Switzerland
  • Baden, Switzerland, 5404
    • Kantonsspital Baden
  • Canton of Aargau
    • Aarau, Canton of Aargau, Switzerland, 5000
      • Tumor Zentrum Aarau
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • University Hospital Basel
• Taiwan
  • Tainan City, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
• United States
  • Illinois
    • Barrington, Illinois, United States, 60010
      • Advocate Good Shepherd Hospital
    • Crystal Lake, Illinois, United States, 60014
      • AMG -Crystal Lake
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor St. Luke's Medical Center
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Medical Center
    • Houston, Texas, United States, 77054
      • Harris Health System - Smith Clinic
    • Houston, Texas, United States, 77054
      • O'Quinn Medical Tower - McNair Campus
    • San Antonio, Texas, United States, 78229
      • START San Antonio

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Postmenopausal women with histologically confirmed HR-positive and HER2-negative BC (per local assessment)
• Documented by estrogen receptor (ER) and/or progesterone receptor (PR)-positive disease by IHC or ISH
• Participants must have Ki-67 score >/=10% with unilateral, invasive T1c-T4c, N0-N2, M0 BC
• Participants must be willing and able to undergo a baseline and Day 14 biopsy and must have an ECOG PS or 0 or 1.
• Participants must be treatment naive for the treatment of BC and cannot have had prior treatment with any systemic therapy (e.g., chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents or use of hormone replacement therapy (HRT) or any other estrogen-containing medication (including vaginal estrogen) within 2 weeks prior to diagnostic tissue sample taken.

Exclusion Criteria:

• No prior systemic therapy, radiation, surgery, investigational therapy for treatment of breast cancer
• Certain medical conditions in the previous 6 months, for example: myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism or other clinically significant episode of thromboembolism
• Lab abnormalities outside protocol specified parameters

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
Experimental: Arm A/Experimental/PF-07220060 plus letrozole; PF-07220060 given as tablet by mouth twice a day for 14 days. Letrozole given as tablet by mouth once a day for 14 days.	Drug: PF-07220060; PF-07220060 given as tablet by mouth twice a day for 14 days.; Drug: letrozole; Letrozole given as tablet by mouth once a day for 14 days; Other Names: Femara
Active Comparator: Arm B/Control/letrozole; Letrozole given by mouth once a day for 14 days.	Drug: letrozole; Letrozole given as tablet by mouth once a day for 14 days; Other Names: Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Ki-67	Centrally assessed biopsy	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)		Baseline, Day 14, and Day 28 post last treatment follow-up visit
Incidence of Serious AEs		Baseline, Day 14, and Day 28 post last treatment follow-up visit
Incidence of AEs leading to Discontinuation		Baseline, Day 14, and Day 28 post last treatment follow-up visit
Ctrough and peri-biopsy plasma concentrations of PF-07220060	Ctrough was defined as pre-dose serum concentration during multiple dosing and observed directly from data.	Pre-dose within 30 minutes and post-dose within 1 hour before or after biopsy
Circulating tumor DNA (ctDNA) measurements	Evaluate response on treatment	Baseline and Day 14
Percentage of Ki-67	All participants will have Ki-67 staining from the biopsy sample on Day 14 and Screening if not previously available	Screening and Day 14

Collaborators and Investigators

• Sponsor: Pfizer
• 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): July 11, 2024
• Primary Completion (Actual): July 10, 2025
• Study Completion (Actual): July 10, 2025

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Neoadjuvant; HR-Positive; Postmenopausal; HER2-negative; Breast Cancer (BC); human epidermal growth factor receptor 2 (HER2); hormone receptor (HR)
• 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
• Other Study ID Numbers: C4391025; 2024-512848-30-00 (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
• product manufactured in and exported from the U.S.: Yes