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A Study to Learn About the Study Medicine Called PF-07248144 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment.

NCT07062965 · Pfizer
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Official title
An Interventional, Open-Label, Randomized, Multicenter, Phase 3 Study of PF-07248144 Plus Fulvestrant Compared to Investigator's Choice of Therapy in Adult Participants With Hormone Receptor-Positive, HER2-Negative Advanced/Metastatic Breast Cancer Whose Disease Progressed After Prior CDK4/6 Inhibitor-based Therapy
About this study
The purpose of this study is to learn about the safety and effects of the study medicine PF-07248144 when given along with fulvestrant for the possible treatment of HR-positive, HER2-negative advanced or metastatic breast cancer. HR-positive breast cancer cells have proteins on their surface called receptors that bind to hormones like estrogen and progesterone (female sex hormones). These hormones can promote the growth of cancer cells. 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. Advanced cancer is a term that is often used to describe cancer that is unlikely to be cured. Metastatic cancer is the type where the cancer cells spread from one part of the body to another. This study is seeking for participants whose breast cancer has gotten worsen after receiving cyclin dependent kinase (CDK) 4/6 inhibitor-based therapy. Half of participants in this study will receive their usual study treatment, everolimus with endocrine therapy (either exemestane or fulvestrant) for HR-positive/HER2-negative advanced or metastatic breast cancer (A/mBC). The study doctor will discuss which hormone therapy is right for the participant before treatment begins. PF-07248144 is a tablet that will be taken by mouth at home every day in a 28-day cycle. Fulvestrant will be given as two injections (one injection in the buttock) at visits to the study clinic. Everolimus and exemestane are also tablets and will be taken by mouth at home every day in a 28-day cycle. The study will compare the experiences of people receiving PF-07248144 in combination with fulvestrant to those of the people who do not. This will help see if PF-07248144 in combination with fulvestrant is safe and effective.
Eligibility criteria
Inclusion Criteria: * Confirmed diagnosis of HR-positive HER2-negative breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent. * Prior CDK4/6 inhibitor therapy in combination with endocrine therapy in advance metastatic setting or in adjuvant setting with documented progression during or within 12 months after the last dose of CDK4/6i. * Participants are eligible if they previously received CDK4/6i or ET as a monotherapy, or in combination for rechallenge therapy in the advance or metastatic setting; have received prior therapy targeting estrogen receptor 1 (ESR1) or breast cancer gene (BRCA)1/2. * 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 (PS) 0 or 1. Exclusion Criteria: * Documented detectable PIK3CA/AKT1/PTEN alterations in tissue * Received greater than two prior lines of systemic therapy in the advance or metastatic setting * Had received any prior chemotherapy, including antibody drug conjugates (ADCs), in advance or metastatic setting. Participants who have previously received chemotherapy in the (neo)adjuvant setting are not excluded from the study. * Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study. * Renal impairment, hepatic dysfunction, or hematologic abnormalities.
Study design
Enrollment target: 400 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-08-05
Estimated completion: 2030-11-04
Last updated: 2026-05-06
Interventions
Drug: PF-07248144Drug: FulvestrantDrug: EverolimusDrug: Exemestane
Primary outcomes
  • Progression Free Survival (PFS) as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (From the date of randomization until disease progression or death due to any cause (up to approximately 2 years))
Sponsor
Pfizer · industry
Contacts & investigators
ContactPfizer CT.gov Call Center · contact · ClinicalTrials.gov_Inquiries@pfizer.com · 1-800-718-1021
InvestigatorPfizer CT.gov Call Center · study_director, Pfizer
All locations (202)
Ironwood Cancer & Research CentersRecruiting
Chandler, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Gilbert, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Glendale, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Goodyear, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Mesa, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Mesa, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Phoenix, Arizona, United States
Ironwood Cancer & Research CentersRecruiting
Scottsdale, Arizona, United States
Ventura County Hematology Oncology SpecialistsNot Yet Recruiting
Camarillo, California, United States
Los Angeles Cancer Network - (Admin Only / Central IDS) - No PatientsNot Yet Recruiting
Glendale, California, United States
Los Angeles Cancer Network - Good SamaritanNot Yet Recruiting
Los Angeles, California, United States
Los Angeles Hematology Oncology Medical GroupNot Yet Recruiting
Los Angeles, California, United States
Rolling Oaks Radiology - OxnardNot Yet Recruiting
Oxnard, California, United States
Ventura County Hematology Oncology SpecialistsNot Yet Recruiting
Oxnard, California, United States
Dr. Manoj Khatore, MD, FACC (Cardiology Practice)Not Yet Recruiting
Oxnard, California, United States
Ventura County Hematology Oncology SpecialistsNot Yet Recruiting
Ventura, California, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Aurora, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Boulder, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Centennial, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Denver, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Englewood, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Lakewood, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Littleton, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Lone Tree, Colorado, United States
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Longmont, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Pueblo, Colorado, United States
Rocky Mountain Cancer Centers LLPNot Yet Recruiting
Thornton, Colorado, United States
Smilow Cancer Hospital - DerbyRecruiting
Derby, Connecticut, United States
Smilow Cancer Hospital - FairfieldRecruiting
Fairfield, Connecticut, United States
Smilow Cancer Hospital - GlastonburyRecruiting
Glastonbury, Connecticut, United States
Smilow Cancer Hospital - GreenwichRecruiting
Greenwich, Connecticut, United States
Smilow Cancer Hospital - GuilfordRecruiting
Guilford, Connecticut, United States
Smilow Cancer Hospital at Saint FrancisRecruiting
Hartford, Connecticut, United States
Smilow Cancer Hospital - Yale New Haven HealthRecruiting
New Haven, Connecticut, United States
Smilow Cancer Hospital - North HavenRecruiting
North Haven, Connecticut, United States
Smilow Cancer Hospital - Long RidgeRecruiting
Stamford, Connecticut, United States
Smilow Cancer Hospital - WaterburyRecruiting
Waterbury, Connecticut, United States
MedStar Washington Hospital CenterNot Yet Recruiting
Washington D.C., District of Columbia, United States
Emory University Hospital MidtownRecruiting
Atlanta, Georgia, United States
Summit Cancer Care, PCRecruiting
Savannah, Georgia, United States
Summit Cancer CareRecruiting
Savannah, Georgia, United States
Memorial Hospital.Recruiting
Shiloh, Illinois, United States
Orchard Healthcare Research Inc.Not Yet Recruiting
Skokie, Illinois, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Annapolis, Maryland, United States
Mfsmc-HjwciNot Yet Recruiting
Baltimore, Maryland, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Bethesda, Maryland, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Columbia, Maryland, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Germantown, Maryland, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Largo, Maryland, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Rockville, Maryland, United States
Maryland Oncology Hematology P.A.Not Yet Recruiting
Silver Spring, Maryland, United States
The Cancer & Hematology CentersRecruiting
Holland, Michigan, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Burnsville, Minnesota, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Coon Rapids, Minnesota, United States
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Edina, Minnesota, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Maple Grove, Minnesota, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Maplewood, Minnesota, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Minneapolis, Minnesota, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Plymouth, Minnesota, United States
Minnesota Oncology Hematology, P.A.Not Yet Recruiting
Woodbury, Minnesota, United States
Siteman Cancer Center - St PetersRecruiting
City of Saint Peters, Missouri, United States
Siteman Cancer Center - North CountyRecruiting
Florissant, Missouri, United States
Saint Luke's Hospital of Kansas CityNot Yet Recruiting
Kansas City, Missouri, United States
Siteman Cancer CenterRecruiting
St Louis, Missouri, United States
Comprehensive Cancer Centers of NevadaNot Yet Recruiting
Henderson, Nevada, United States
Comprehensive Cancer Centers of NevadaNot Yet Recruiting
Henderson, Nevada, United States
Comprehensive Cancer Centers of NevadaNot Yet Recruiting
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of NevadaNot Yet Recruiting
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of NevadaNot Yet Recruiting
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of NevadaNot Yet Recruiting
Las Vegas, Nevada, United States
Hackensack University Medical CenterNot Yet Recruiting
Hackensack, New Jersey, United States
The West Clinic, PLLC dba West Cancer CenterNot Yet Recruiting
Germantown, Tennessee, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
Henry-Joyce Cancer ClinicRecruiting
Nashville, Tennessee, United States
Texas Oncology-Northeast TexasRecruiting
Allen, Texas, United States
Texas Oncology - Central South (Balcones Dr)Recruiting
Austin, Texas, United States
Texas Oncology - Central South (James Casey)Recruiting
Austin, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Denison, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Denton, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Flower Mound, Texas, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
MD Anderson West HoustonRecruiting
Houston, Texas, United States
US Oncology Investigational Product Center (IPC)Recruiting
Irving, Texas, United States
US Oncology Investigational Products CenterRecruiting
Irving, Texas, United States
MD Anderson League CityRecruiting
League City, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Lewisville, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Longview, Texas, United States
Texas Oncology - Central South (South 2nd)Recruiting
McAllen, Texas, United States
Texas Oncology-Northeast TexasRecruiting
McKinney, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Palestine, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Paris, Texas, United States
Texas Oncology-Northeast TexasRecruiting
Tyler, Texas, United States
Huntsman Cancer InstituteRecruiting
Salt Lake City, Utah, United States
Virginia Oncology AssociatesNot Yet Recruiting
Chesapeake, Virginia, United States
Virginia Cancer SpecialistsNot Yet Recruiting
Manassas, Virginia, United States
Bon Secours Cancer Institute at Memorial Regional Medical CenterRecruiting
Mechanicsville, Virginia, United States
Virginia Cancer Specialists, PCNot Yet Recruiting
Reston, Virginia, United States
Virginia Oncology AssociatesNot Yet Recruiting
Virginia Beach, Virginia, United States
Virginia Oncology AssociatesNot Yet Recruiting
Williamsburg, Virginia, United States
Fred Hutchinson Cancer CenterNot Yet Recruiting
Seattle, Washington, United States
ICON Cancer Centre - Kurralta ParkNot Yet Recruiting
Kurralta Park, South Australia, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
Western Health-Sunshine & Footscray HospitalsRecruiting
St Albans, Victoria, Australia
Algemeen Ziekenhuis klinaRecruiting
Brasschaat, Antwerpen, Belgium
Institut Jules BordetRecruiting
Anderlecht, Bruxelles-capitale, Région de, Belgium
Cliniques universitaires Saint-LucNot Yet Recruiting
Brussels, Bruxelles-capitale, Région de, Belgium
AZ Groeninge Campus KennedylaanRecruiting
Kortrijk, West-vlaanderen, Belgium
Afecc Associacao Feminina Educacao Combate CancerRecruiting
Vitória, Espírito Santo, Brazil
ONCOSITE - Centro de Pesquisa Clinica em OncologiaRecruiting
Ijuí, Rio Grande do Sul, Brazil
Hospital São Lucas da PUCRSNot Yet Recruiting
Porto Alegre, Rio Grande do Sul, Brazil
ANIMI - Unidade de Tratamento OncologicoRecruiting
Lages, Santa Catarina, Brazil
IBCC - Núcleo de Pesquisa e EnsinoNot Yet Recruiting
São Paulo, Brazil
Multiprofile Hospital for Active Treatment Serdikamed EOODRecruiting
Sofia, Sofia (stolitsa), Bulgaria
Specialized Hospital for Active Treatment of Oncology - HaskovoRecruiting
Haskovo, Bulgaria
Complex Oncology Center - ShumenRecruiting
Shumen, Bulgaria
Centre Hospitalier de l'Université de MontréalNot Yet Recruiting
Montreal, Quebec, Canada
CHU de Québec-Université Laval, Hôpital du Saint-SacrementRecruiting
Québec, Quebec, Canada
CHU de Québec-Université LavalRecruiting
Québec, Canada
Anhui Provincial Cancer HospitalRecruiting
Hefei, Anhui, China
Fujian Medical University Union HospitalRecruiting
Fuzhou, Fujian, China
Sun Yat-sen University Cancer CenterRecruiting
Guangzhou, Guangdong, China
Southern Medical University Nanfang HospitalRecruiting
Guangzhou, Guangdong, China
Affiliated Hospital of Hebei UniversityNot Yet Recruiting
Baoding, Hebei, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and TechnologyRecruiting
Wuhan, Hubei, China
Hunan Cancer HospitalNot Yet Recruiting
Changsha, Hunan, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical SchoolRecruiting
Nanjing, Jiangsu, China
The 2nd Affiliated Hospital of Dalian Medical UniversityRecruiting
Dalian, Liaoning, China
Shandong Cancer HospitalRecruiting
Jinan, Shandong, China
Fudan University Shanghai Cancer CenterRecruiting
Shanghai, Shanghai Municipality, China
Fakultni Thomayerova nemocniceRecruiting
Prague, Praha 4, Czechia
Fakultni nemocnice v MotoleRecruiting
Prague, Praha 5, Czechia
Nemocnice AGEL Novy Jicin a.s.Recruiting
Nový Jičín, Czechia
Kuopion Yliopistollinen SairaalaRecruiting
Kuopio, Northern Savonia, Finland
Tampereen yliopistollinen sairaalaRecruiting
Tampere, Pirkanmaa, Finland
Docrates SyöpäsairaalaRecruiting
Helsinki, Uusimaa, Finland
Centre Eugène Marquis Rennes - Centre de Lutte Contre le CancerNot Yet Recruiting
Rennes, Brittany Region, France
Institut Régional du Cancer MontpellierNot Yet Recruiting
Montpellier, Hérault, France
Institut de Cancérologie de Lorraine Alexis VautrinNot Yet Recruiting
Vandœuvre-lès-Nancy, Lorraine, France
Hôpital de la Croix-RousseNot Yet Recruiting
Lyon, Rhône, France
Centre Hospitalier Lyon SudNot Yet Recruiting
Pierre-Bénite, Rhône, France
Institut BergoniéNot Yet Recruiting
Bordeaux, France
Centre François BaclesseNot Yet Recruiting
Caen, France
Universitätsklinik UlmNot Yet Recruiting
Ulm, Baden-Wurttemberg, Germany
Universitaetsklinikum ErlangenRecruiting
Erlangen, Bavaria, Germany
Charité Universitaetsmedizin Berlin - Campus MitteRecruiting
Berlin, Germany
Mammazentrum HH am Krankenhaus JerusalemNot Yet Recruiting
Hamburg, Germany
IASO General ClinicRecruiting
Athens, Attica, Greece
Hygeia HospitalRecruiting
Marousi, Attikí, Greece
University General Hospital of HeraklionRecruiting
Heraklion, Irakleío, Greece
Semmelweis EgyetemNot Yet Recruiting
Budapest, Hungary
Debreceni Egyetem Klinikai KozpontNot Yet Recruiting
Debrecen, Hungary
Nirmal Hospital Pvt Ltd.Recruiting
Surat, Gujarat, India
Spandana Oncology Centre (SOC)Recruiting
Bengaluru, Karnataka, India
Apex Wellness HospitalNot Yet Recruiting
Nashik, Maharashtra, India
Sahyadri Super Speciality HospitalNot Yet Recruiting
Pune, Maharashtra, India
Rabin Medical CenterRecruiting
Petah Tikva, Central District, Israel
Shaare Zedek Medical CenterRecruiting
Jerusalem, Jerusalem, Israel
Hadassah Medical CenterRecruiting
Jerusalem, Jerusalem, Israel
Rambam Health Care CampusRecruiting
Haifa, Northern District, Israel
Sourasky Medical CenterNot Yet Recruiting
Tel Aviv, TELL ABĪB, Israel
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'OrsolaRecruiting
Bologna, Emilia-Romagna, Italy
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"Recruiting
Meldola, Emilia-Romagna, Italy
Istituto Nazionale dei Tumori IRCCS Fondazione G PascaleNot Yet Recruiting
Naples, Naples, Italy
Ospedale San RaffaeleNot Yet Recruiting
Milan, Italy
National Cancer Center Hospital EastRecruiting
Kashiwa, Chiba, Japan
Gunma Prefectural Cancer CenterRecruiting
Otashi, Gunma, Japan
Tokai University HospitalRecruiting
Isehara, Kanagawa, Japan
Kanagawa cancer centerRecruiting
Yokohama, Kanagawa, Japan
Juntendo University HospitalRecruiting
Bunkyo-ku, Tokyo, Japan
National Hospital Organization Kyushu Cancer CenterRecruiting
Fukuoka, Japan
Showa Medical University HospitalRecruiting
Tokyo, Japan
Centro de Investigacion Clinica de OaxacaRecruiting
Oaxaca City, Oaxaca, Mexico
COI Centro Oncologico Internacional S.A.P.I. de C.V.Recruiting
Mexico City, Mexico
Franciscus Vlietland ZiekenhuisRecruiting
Schiedam, South Holland, Netherlands
Centrum Onkologii im. Prof. Franciszka LukaszczykaNot Yet Recruiting
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o.Not Yet Recruiting
Krakow, Lesser Poland Voivodeship, Poland
Onkologicky Ustav sv. AlzbetyRecruiting
Bratislava, Bratislava Region, Slovakia
Vychodoslovensky Onkologicky ustav a.s.Recruiting
Košice, Košice Region, Slovakia
Narodny onkologicky ustavRecruiting
Bratislava, Slovakia
Seoul National University Bundang HospitalRecruiting
Seongnam-si, Kyǒnggi-do, South Korea
Gangnam Severance Hospital, Yonsei University Health SystemRecruiting
Gangnam-gu, Seoul-teukbyeolsi [seoul], South Korea
Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Samsung Medical CenterRecruiting
Seoul, Seoul-teukbyeolsi [seoul], South Korea
CHUAC-Complejo Hospitalario Universitario A CoruñaRecruiting
A Coruña, A Coruña [LA Coruña], Spain
Hospital Universitari Vall d'HebronRecruiting
Barcelona, Barcelona [barcelona], Spain
Osi Bilbao-BasurtoRecruiting
Bilbao, Basque Country, Spain
Hospital Clínic de BarcelonaRecruiting
Barcelona, Catalunya [cataluña], Spain
Hospital Universitario Virgen de la VictoriaRecruiting
Málaga, Málaga, Spain
Hospital Universitario San CecilioRecruiting
Granada, Spain
Hospital Universitario de JaenRecruiting
Jaén, Spain
Hospital Universitario Miguel ServetRecruiting
Zaragoza, Spain
SödersjukhusetRecruiting
Stockholm, Stockholms LÄN [se-01], Sweden
Sahlgrenska UniversitetssjukhusetRecruiting
Gothenburg, Sweden
Chi Mei Medical CenterRecruiting
Tainan, Tainan, Taiwan
Taipei Veterans General HospitalRecruiting
Taipei, Taiwan
Medipol Mega Universite HastanesiRecruiting
Istanbul, İ̇stanbul, Turkey (Türkiye)
Memorial Ankara HastanesiRecruiting
Ankara, Turkey (Türkiye)
Ankara Bilkent Şehir HastanesiRecruiting
Ankara, Turkey (Türkiye)
Dicle ÜniversitesiRecruiting
Diyarbakır, Turkey (Türkiye)
Musgrove Park HospitalNot Yet Recruiting
Taunton, Somerset, United Kingdom
A Study to Learn About the Study Medicine Called PF-07248144 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment. · TrialPath