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 Cancérologie 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 Carita
  • 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, 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
Percentage of Participants With Complete Cell Cycle Arrest (CCCA) at Day 14	CCCA was determined by antigen Kiel 67 (Ki-67) value as decided by Sponsor. Ki-67 was extensively used as a prognostic and predictive biomarker for cancer diagnosis and treatment. Ki-67 expression was measured by immunohistochemistry. Assessment at Day 14 was done in blinded manner by centrally assessed biopsy.	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity and was congenital anomaly/birth defect. AEs that occurred on or after the first dose of study treatment and before the end of treatment (35 days after last dose of study treatment or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first) was considered TEAEs. All AEs (SAEs and all other AEs) were considered for evaluation.	From start of study intervention (Day 1) up to 35 days after the last dose of study intervention or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first (approximately up to 49 days)
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity and was congenital anomaly/birth defect. AEs that occurred on or after the first dose of study treatment and before the end of treatment (35 days after last dose of study treatment or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first) was considered TEAEs.	From start of study intervention (Day 1) up to 35 days after the last dose of study intervention or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first (approximately up to 49 days)
Number of Participant With AEs Leading to Any Study Intervention Discontinuation	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	During study treatment (maximum up to 14 days)
Circulating Tumor Deoxyribonucleic Acid (ctDNA) Methylation Tumor Fraction Values at Baseline and Day 14	The methylation-based tumor fraction of a single sample was estimated from methylation signals across targeted regions from the methylation panel, was calibrated using training data including cancer free donors and participants with mixed cancer types. The method included a data-informed differentially methylated region selection targeting regions with high pan cancer signal to noise ratio. This value was an estimate of the proportion of the sample that was tumor derived and expressed as percentage of DNA. ctDNA methylation tumor fraction values were reported in percentage at Baseline and Day 14 were assessed from central laboratory.	Baseline (the last measurement on or prior to date of the first dose of study intervention if the first dose is not missing, otherwise, on or prior to the randomization date), Day 14 (pre-dose)
Plasma Concentration (Ctrough) of PF-07220060 on Day 14	Ctrough was pre-dose plasma concentration.	Pre-dose (within 30 minutes before dosing) on Day 14
Plasma Concentration at the Time of Biopsy (Cperi-biopsy) of PF-07220060 on Day 14	Cperi-biopsy was plasma concentration at the time of biopsy.	Within 1 hour before or 1 hour after biopsy on Day 14
Change From Baseline in Antigen Ki-67 at Day 14	Ki-67 was extensively used as a prognostic and predictive biomarker for cancer diagnosis and treatment. Ki-67 expression was measured by immunohistochemistry and expressed as percentage of cells. Assessment at baseline and Day 14 was done in blinded manner by centrally assessed biopsy.	Baseline (the last measurement on or prior to date of the first dose of study intervention if the first dose was not missing, otherwise, on or prior to the randomization date), Day 14 (pre-dose)
Relative Reduction (%) of Ki-67 From Baseline at Day 14	Ki-67 was extensively used as a prognostic and predictive biomarker for cancer diagnosis and treatment. Ki-67 expression was measured by immunohistochemistry. Assessment at baseline and Day 14 was done in blinded manner by centrally assessed biopsy. Relative reduction at Day 14 was calculated as:100 *(1-Ki-67 at Day 14/Ki-67 at Baseline). Relative reduction was expressed in percentage reduction.	Baseline (the last measurement on or prior to date of the first dose of study intervention if the first dose was not missing, otherwise, on or prior to the randomization date), Day 14 (pre-dose)

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 (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

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