Clinical trial NCT06760637: 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
Official title: AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER PHASE 3 STUDY OF PF-07220060 PLUS LETROZOLE COMPARED TO CDK4/6 INHIBITOR PLUS LETROZOLE IN PARTICIPANTS OVER 18 YEARS OF AGE WITH HORMONE RECEPTOR (HR)-POSITIVE, HER2-NEGATIVE ADVANCED/METASTATIC BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTICANCER TREATMENT FOR ADVANCED/METASTATIC DISEASE (FOURLIGHT-3)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2025-01-07
Enrollment: 1020
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study participants will be randomly assigned into 1 of 2 groups in parallel for the entire duration of the study. The experimental arm will receive PF-07220060 and letrozole (Arm A) while the comparator arm with receive the study doctors choice of CDK4/6i and letrozole (Arm B).
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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:

* 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.

Primary outcomes:
measure: Progression Free Survival (PFS) by BICR
timeFrame: From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization until death due to any cause (up to approximately 13 years).
measure: Progression Free Survival (PFS) by Investigator
timeFrame: From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)
measure: OR by BICR and by investigator
timeFrame: From randomization to progression or death whichever occurs first (up to approximately 4 years)
measure: Duration of Response (DoR) by BICR and by investigator
timeFrame: From the date of CR or PR until objective progressive disease, or death (up to approximately 4 years)
measure: Incidence of treatment emergent treatment relatedadverse events (AE)
timeFrame: Duration of the study approximately up to 13 years.
measure: Incidence of treatment emergent treatment relatedserious adverse events
timeFrame: Duration of the study approximately up to 13 years.
measure: Estimated mean change from baseline in EORTC QLQ C30
timeFrame: Baseline to end of treatment (up to approximately 4 years)
measure: Estimated mean change from baseline in BPI-SF
timeFrame: Baseline to end of treatment (up to approximately 4 years)
measure: Estimated mean change from baseline in EQ-5D-5L
timeFrame: Baseline to end of treatment (up to approximately 4 years)
measure: Estimated mean change from baseline in EORTC Breast Cancer Module (BR42)
timeFrame: Baseline to end of treatment (up to approximately 4 years)
measure: Mean change from baseline of ctDNA
timeFrame: Baseline to end of treatment (up to approximately 4 years)
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Gilbert
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Glendale
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Mesa
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Mesa
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Phoenix
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Scottsdale
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Alamitos
country: United States
facility: Cancer and Blood Research Center, LLC
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic / Cancer and Blood Research Center, LLC
state: California
city: Torrance
country: United States
facility: Cancer AND Blood Specialty Clinic
state: California
city: Golden
country: United States
facility: Intermountain Health Lutheran Hospital
state: Colorado
city: Golden
country: United States
facility: Lutheran Hospital - Cancer Centers of Colorado
state: Colorado
city: Grand Junction
country: United States
facility: Cancer Centers of Colorado St. Mary's Regional Hospital
state: Colorado
city: Grand Junction
country: United States
facility: Intermountain Health Saint Mary's Regional Hospital
state: Colorado
city: Grand Junction
country: United States
facility: Intermountain Health
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Altamonte Springs
country: United States
facility: AdventHealth Altamonte Infusion Center
state: Florida
city: Altamonte Springs
country: United States
facility: AdventHealth Altamonte Springs
state: Florida
city: Altamonte Springs
country: United States
facility: AdventHealth Medical Group Altamonte
state: Florida
city: Aventura
country: United States
facility: Mount Sinai Medical Center, Aventura
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: AdventHealth Medical Group Orlando
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando Infusion Center
state: Florida
city: Savannah
country: United States
facility: Summit Cancer Care, PC
state: Georgia
city: Elmhurst
country: United States
facility: Endeavor Health
state: Illinois
city: Evanston
country: United States
facility: Ascension Illinois - Evanston Infusion Center
state: Illinois
city: Naperville
country: United States
facility: Endeavor Health
state: Illinois
city: Skokie
country: United States
facility: Ascension Illinois-Skokie Infusion Center
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: Annapolis
country: United States
facility: Velocity Clinical Research
state: Maryland
city: Baltimore
country: United States
facility: Mercy Medical Center - Baltimore
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Newton
country: United States
facility: Dana-Farber Cancer Institute - Chestnut Hill
state: Massachusetts
city: Coon Rapids
country: United States
facility: Allina Health Cancer Institute - Mercy Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute - Abbott Northwestern Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Allina Health Cancer Institute - United Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Reno
country: United States
facility: Renown Health
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center Investigational Drug Services
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Investigational Drug Service - Westside
state: Oregon
city: Portland
country: United States
facility: Providence Oncology and Hematology Care Clinic - Westside
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler on behalf of UT Health East Texas HOPE Cancer
state: Texas
city: Douglas
country: Australia
facility: Townsville University Hospital
state: Queensland
city: Capel Sound
country: Australia
facility: Rosebud Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdika EOOD
state: Sofia (stolitsa)
city: Burgas
country: Bulgaria
facility: Complex Oncology Center - Burgas
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Dr. Tota Venkova AD
city: Haskovo
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology - Haskovo
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv EOOD
city: Shumen
country: Bulgaria
facility: Complex Oncology Center - Shumen
city: Fredericton
country: Canada
facility: Dr. Everett Chalmers Regional Hospital
state: New Brunswick
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer hospital
state: Beijing
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The 2nd Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Linhai
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
state: Praha 5
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Hovedstaden
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby
state: Midtjylland
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala
state: Pirkanmaa
city: Vaasa
country: Finland
facility: Vaasan Keskussairaala
state: Pohjanmaa
city: Helsinki
country: Finland
facility: Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
state: Uusimaa
city: Turku
country: Finland
facility: Turku University Hospital
state: Varsinais-suomi
city: La Roche-sur-Yon
country: France
facility: CHD Vendee
state: Vendée
city: Koblenz
country: Germany
facility: InVO Institut für Versorgungsforschung in der Onkologie
state: Rheinland-pfalz
city: Marousi
country: Greece
facility: Hygeia Hospital
state: Attikí
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Institute And Research Centre
state: Delhi
city: Surat
country: India
facility: Nirmal Hospital Pvt Ltd.
state: Gujarat
city: Gurugram
country: India
facility: Artemis hospital
state: Haryana
city: Bangalore
country: India
facility: Spandana Oncology Centre (SOC)
state: Karnataka
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Nashik
country: India
facility: Apex Wellness Hospital
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Thane
country: India
facility: Bhakti Vedanta Hospital and Research Institute
state: Maharashtra
city: Hyderabad
country: India
facility: Basavatarakam Indo American Cancer Hospital & Research Institute
state: Telangana
city: Kolkata
country: India
facility: Apollo Multispeciality Hospitals limited
state: WEST Bengal
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
state: Hamerkaz
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Hatsafon
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
state: Tell Abīb
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carità
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Otashi
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Yokohama
country: Japan
facility: Kanagawa cancer center
state: Kanagawa
city: Sakyo-ku
country: Japan
facility: Kyoto University Hospital
state: Kyoto
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Shinagawa
country: Japan
facility: Showa University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
state: Tokyo
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Kumamoto
country: Japan
facility: Kumamoto Shinto General Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Kraków
country: Poland
facility: Pratia MCM Krakow
state: Małopolskie
city: Skórzewo
country: Poland
facility: AIDPORT Sp. z o.o.
state: Wielkopolskie
city: Łódź
country: Poland
facility: Instytut MSF Sp zoo
state: Łódzkie
city: Komarno
country: Slovakia
facility: Nemocnica AGEL Komarno
state: Nitriansky KRAJ
city: Banka
country: Slovakia
facility: Medeon, s.r.o.
state: Trnavský KRAJ
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Málaga
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
city: Gävle
country: Sweden
facility: Sjukhuset I Gävle
state: Gävleborgs LÄN [se-21]
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
state: Uppsala LÄN [se-03]
city: Västerås
country: Sweden
facility: Västmanlands Sjukhus Västerås
state: Västmanlands LÄN [se-19]
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
state: Västra Götalands LÄN [se-14]
city: Jönköping
country: Sweden
facility: Lanssjukhuset Ryhov
city: Sundsvall
country: Sweden
facility: Sundsvalls Sjukhus
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Zhu Bei City
country: Taiwan
facility: National Taiwan University Hospital - Hsinchu branch
state: Hsinchu
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch
city: Istanbul
country: Turkey
facility: İ.A.Ü VM Medical Park Florya Hastanesi
state: İ̇stanbul
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Diyarbakir
country: Turkey
facility: Dicle Üniversitesi
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: London, CITY OF
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: