CClinicalTrials.gg
Active, not recruitingNCT06760637FourLight-3Updated May 19, 2026

Study of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease

A Phase 3 interventional study of PF-07220060 and letrozole in Breast Cancer, sponsored by Pfizer. Active, not recruiting at 463 sites in 30 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-19.

Sponsored by Pfizer · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,035
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the safety and efficacy of PF-07220060 with letrozole compared to approved treatments (ie, palbociclib, ribociclib or abemaciclib with letrozole) in people with breast cancer:

  • HR-positive (breast cancer cells that need estrogen or progesterone to grow)
  • HER2-negative (cells that have a small amount or none of a protein called HER2 on their surface);
  • locally advanced (that has spread from where it started to nearby tissue or lymph nodes) or metastatic disease (the spread of cancer to other places in the body)
  • who have not received any prior systemic anti-cancer treatment for advanced/metastatic disease.

Approximately half of the participants will receive PF-07220060 plus letrozole while the other half of participants will receive the investigator's choice of treatment plus letrozole.

The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

02

Conditions studied

  • Breast Cancer

Keywords

  • Locally advanced or metastatic breast cancer
  • Estrogen receptor positive [ER(+)]
  • Progesterone receptor positive [PR(+)]
  • Hormone receptor positive [HR(+)]
  • Human epidermal growth factor receptor 2 negative [HER2(-)]
  • ER(+)/HER2(-)
  • PR(+)/HER2(-)
  • HR(+)/HER2(-)
  • Advanced Breast Cancer
  • Breast tumor
  • Breast cancer
  • Palbociclib
  • Abemaciclib
  • Ribociclib
  • Partial Response+ (PR+)
  • Metastatic breast cancer
  • Hormone Therapy
  • Hormone positive breast cancer
  • Recurrent breast cancer
  • HR+
  • HER2-negative
  • Relapse
  • Recurrent
  • First line treatment
  • Left Sided Breast Cancer
  • Left-Sided Breast Cancer
  • Right Sided Breast Cancer
  • Right-Sided Breast Cancer
  • Unilateral Breast Cancer
  • Cancer of the breast
  • CDK4i
  • CDK4/6i
  • Bilateral Breast Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histological confirmation of breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent.
  • Documented estrogen receptor (ER) and/or progesterone receptor (PR)-positive tumor
  • Documented HER2-negative tumor
  • Previously untreated with any systemic anticancer therapy for their locally advanced or metastatic disease.
  • Measurable disease or non-measurable bone only disease as defined by RECIST version 1.1

Exclusion criteria

Exclusion Criteria:

  • In visceral crisis at risk of immediately life-threatening complications in the short term.
  • Current or past history of central nervous system metastases.
  • Have received prior (neo)adjuvant endocrine therapy (ET) and had recurrence during or within 12 months after the last dose of ET.
  • Have received prior (neo)adjuvant CDK4/6i and had recurrence during or within 12 months after the last dose of CDK4/6i.
  • Inadequate renal function, hepatic dysfunction, or hematologic abnormalities.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,035 participants (actual)

Study arms

  • Experimental
    Arm A

    PF-07220060 tablet taken by mouth plus Letrozole tablet taken by mouth

    Drug: PF-07220060 · Drug: letrozole

  • Active comparator
    Arm B

    Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth

    Drug: letrozole · Drug: abemaciclib · Drug: palbociclib · Drug: ribociclib

Interventions

  • DrugPF-07220060

    CDK4 inhibitor

  • Drugletrozole

    endocrine therapy

  • Drugabemaciclib

    CDK4/6 inhibitor

  • Drugpalbociclib

    CDK4/6 inhibitor

  • Drugribociclib

    CDK4/6 inhibitor

05

What researchers measure

Primary outcomes

  1. Progression Free Survival (PFS) by BICR

    Time from the date of randomization to the date of the first documentation of objective progressive disease as determined by blinded independent central review (BICR) per RECIST v1.1, or death due to any cause, whichever occurs first

    Time frame: From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)

Secondary outcomes

  1. Overall Survival (OS)

    Time from the date of randomization to the date of death due to any cause

    Time frame: From the date of randomization until death due to any cause (up to approximately 13 years).

  2. Progression Free Survival (PFS) by Investigator

    Time from the date of randomization to the date of the first documentation of objective progressive disease as determined by investigator per RECIST v1.1, or death due to any cause, whichever occurs first

    Time frame: From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)

  3. OR by BICR and by investigator

    Time from randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) to the date of progression OR death whichever occurs first

    Time frame: From randomization to progression or death whichever occurs first (up to approximately 4 years)

  4. Duration of Response (DoR) by BICR and by investigator

    Time from the date of CR or PR to the first documentation of objective progressive disease, or death due to any cause, whichever occurs first

    Time frame: From the date of CR or PR until objective progressive disease, or death (up to approximately 4 years)

  5. Incidence of treatment emergent treatment related adverse events (AE)

    Incidence and severity of AEs graded according to the NCI CTCAE v5.0

    Time frame: Duration of the study approximately up to 13 years.

  6. Incidence of treatment emergent treatment related serious adverse events

    Incidence and severity of AEs graded according to NCI CTCAE v5.0

    Time frame: Duration of the study approximately up to 13 years.

  7. Estimated mean change from baseline in EORTC QLQ C30

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  8. Estimated mean change from baseline in BPI-SF

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  9. Estimated mean change from baseline in EQ-5D-5L

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  10. Estimated mean change from baseline in EORTC Breast Cancer Module (BR42)

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  11. Mean change from baseline of ctDNA

    Time frame: Baseline to end of treatment (up to approximately 4 years)

06

Study locations

463 sites
  • The Kirklin Clinic of UAB Hospital
    Birmingham, Alabama 35233, United States
  • The University of Alabama at Birmingham
    Birmingham, Alabama 35249, United States
  • University of Alabama at Birmingham Hospital
    Birmingham, Alabama 35249, United States
  • Ironwood Cancer & Research Centers
    Chandler, Arizona 85224, United States
  • Ironwood Cancer & Research Centers
    Gilbert, Arizona 85297, United States
  • Ironwood Cancer & Research Centers
    Glendale, Arizona 85306, United States
  • Ironwood Cancer & Research Centers
    Goodyear, Arizona 85395, United States
  • Ironwood Cancer & Research Centers
    Mesa, Arizona 85202, United States
  • Ironwood Cancer & Research Centers
    Mesa, Arizona 85206, United States
  • Ironwood Cancer & Research Centers
    Phoenix, Arizona 85028, United States
  • Ironwood Cancer & Research Centers
    Scottsdale, Arizona 85260, United States
  • CARTI Cancer Center Saline County
    Bryant, Arkansas 72022, United States
  • CARTI Cancer Center Conway
    Conway, Arkansas 72034, United States
  • Highlands Oncology
    Fayetteville, Arkansas 72703, United States
  • CARTI Cancer Center
    Little Rock, Arkansas 72205, United States
  • CARTI Cancer Center North Little Rock Urology
    North Little Rock, Arkansas 72117, United States
  • CARTI Cancer Center North Little Rock
    North Little Rock, Arkansas 72117, United States
  • CARTI Cancer Center Pine Bluff
    Pine Bluff, Arkansas 71603, United States
  • Highlands Oncology
    Rogers, Arkansas 72758, United States
  • Highlands Oncology Group
    Springdale, Arkansas 72762, United States
  • Providence Medical Foundation
    Anaheim, California 92805, United States
  • Sutter Auburn Faith Hospital
    Auburn, California 95602, United States
  • Sutter Health Alta Bates
    Berkeley, California 94704, United States
  • Cedars-Sinai Cancer Beverly Hills (drug treatment and dispensing location)
    Beverly Hills, California 90211, United States
  • Cedars-Sinai Cancer Beverly Hills
    Beverly Hills, California 90211, United States
  • Marshall Cancer Center
    Cameron Park, California 95682, United States
  • Enloe Medical Center
    Chico, California 95926, United States
  • Enloe Regional Cancer Center
    Chico, California 95926, United States
  • City of Hope Investigational Drug Service (IDS)
    Duarte, California 91010, United States
  • City of Hope(City of Hope National Medical Center,City of Hope Medical Center)
    Duarte, California 91010, United States
  • UCSF Washington Hospital Cancer Center/ Washington Hospital Healthcare System
    Fremont, California 94538, United States
  • Premier Cancer Care and Infusion Center - Fresno - North Thesta Street
    Fresno, California 93710, United States
  • Providence Medical Foundation
    Fullerton, California 92835, United States
  • Providence St. Jude Medical Center
    Fullerton, California 92835, United States
  • City of Hope - Seacliff
    Huntington Beach, California 92648, United States
  • City of Hope at Irvine Lennar
    Irvine, California 92618, United States
  • City of Hope Investigational Drug Service (IDS)
    Irvine, California 92618, United States
  • Hoag Health Center Irvine
    Irvine, California 92618, United States
  • Hoag Hospital Irvine
    Irvine, California 92618, United States
  • City of Hope-Antelope Valley
    Lancaster, California 93534, United States
  • City of Hope at Long Beach Elm
    Long Beach, California 90813, United States
  • Cancer and Blood Research Center, LLC
    Los Alamitos, California 90720, United States
  • Cancer and Blood Specialty Clinic / Cancer and Blood Research Center, LLC
    Los Alamitos, California 90720, United States
  • Keck Hospital of USC
    Los Angeles, California 90033, United States
  • Los Angeles General Medical Center
    Los Angeles, California 90033, United States
  • Norris Healthcare Center 3 (HC3)
    Los Angeles, California 90033, United States
  • USC/Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • Cedars-Sinai Cancer at Cedars-Sinai Medical Center (drug treatment and dispensing location)
    Los Angeles, California 90048, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • Ellison Medical Institute
    Los Angeles, California 90064, United States
  • UCLA Department of Medicine - Hematology/Oncology
    Los Angeles, California 90095, United States
  • Hoag Memorial Hospital Presbyterian
    Newport Beach, California 92663, United States
  • Keck Medicine of USC Norris Oncology/Hematology - Newport Beach Treatment Center
    Newport Beach, California 92663, United States
  • USC Norris Oncology/Hematology - Newport Beach
    Newport Beach, California 92663, United States
  • Sutter Health Palo Alto
    Palo Alto, California 94301, United States
  • Clinical and Translational Research Unit (CTRU)
    Palo Alto, California 94304, United States
  • Stanford Cancer Center
    Palo Alto, California 94304, United States
  • Stanford Women's Cancer Center
    Palo Alto, California 94304, United States
  • Keck Medical Center of USC Pasadena
    Pasadena, California 91105, United States
  • Marshall Hospital
    Placerville, California 95667, United States
  • UCLA Hematology/Oncology - Porter Ranch
    Porter Ranch, California 91326, United States
  • Sutter Roseville Medical Center
    Roseville, California 95661, United States
  • Sutter Health - Sutter Institute for Medical Research
    Sacramento, California 95816, United States
  • University of California Davis (UC Davis) Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • University of California Davis Medical Center
    Sacramento, California 95817, United States
  • University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
    San Francisco, California 94158, United States
  • UCLA Hematology/Oncology - San Luis Obispo
    San Luis Obispo, California 93401, United States
  • Tower Saint John's Imaging
    Santa Monica, California 90403, United States
  • Providence Saint John's Health Center
    Santa Monica, California 90404, United States
  • UCLA Hematology/Oncology - Parkside
    Santa Monica, California 90404, United States
  • UCLA Hematology/Oncology - Santa Monica
    Santa Monica, California 90404, United States
  • City of Hope-South Pasadena
    South Pasadena, California 91030, United States
  • Stanford Health Care, Investigational Drug Service
    Stanford, California 94305, United States
  • Sutter Health Sunnyvale
    Sunnyvale, California 94086, United States
  • Cedars-Sinai Cancer Tarzana
    Tarzana, California 91356, United States
  • Cancer AND Blood Specialty Clinic
    Torrance, California 90505, United States
  • Hunt Cancer Institute, an Affiliate of Cedars-Sinai Cancer
    Torrance, California 90505, United States
  • Tahoe Forest Cancer Center
    Truckee, California 96161, United States
  • City of Hope - Upland
    Upland, California 91786, United States
  • Wellness Oncology Hematology
    West Hills, California 91307, United States
  • Breast Health Services Building
    West Hollywood, California 90048, United States
  • UCLA Hematology/Oncology - Westlake
    Westlake Village, California 91361, United States
  • Denver Health and Hospital Authority
    Denver, Colorado 80204, United States
  • Intermountain Health Lutheran Hospital
    Golden, Colorado 80401, United States
  • Lutheran Hospital - Cancer Centers of Colorado
    Golden, Colorado 80401, United States
  • Cancer Centers of Colorado St. Mary's Regional Hospital
    Grand Junction, Colorado 81501, United States
  • Intermountain Health Saint Mary's Regional Hospital
    Grand Junction, Colorado 81501, United States
  • Intermountain Health
    Grand Junction, Colorado 81505, United States
  • MedStar Washington Hospital Center
    Washington D.C., District of Columbia 20010, United States
  • AdventHealth Altamonte Infusion Center
    Altamonte Springs, Florida 32701, United States
  • AdventHealth Altamonte Springs
    Altamonte Springs, Florida 32701, United States
  • AdventHealth Medical Group Altamonte
    Altamonte Springs, Florida 32701, United States
  • Boca Raton Regional Hospital
    Boca Raton, Florida 33486, United States
  • Baptist MD Anderson Cancer Center
    Jacksonville, Florida 32207, United States
  • AdventHealth Orlando
    Orlando, Florida 32803, United States
  • AdventHealth Medical Group Orlando
    Orlando, Florida 32804, United States
  • AdventHealth Orlando Infusion Center
    Orlando, Florida 32804, United States
  • Summit Cancer Care, PC
    Savannah, Georgia 31405, United States
  • St. Luke's Cancer Institute: Boise
    Boise, Idaho 83712, United States
  • St. Luke's Regional Medical Center
    Boise, Idaho 83712, United States

Showing the first 100 of 463 sites across 30 countries.

07

References and documents

Individual participant data

Plan to share: 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.

08

Registry details

Key details

Study ID
NCT06760637
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Jan 7, 2025
Start date
Jan 6, 2025
Primary completion
Jan 2, 2029 (estimated)
Completion
Dec 29, 2037 (estimated)
Last update
May 19, 2026

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion