A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)

April 17, 2026 updated by: Seagen, a wholly owned subsidiary of Pfizer

A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)

This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).

In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.

All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Control arm: Placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days

Experimental arm: Tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days

Trastuzumab and pertuzumab will be administered as follows:

• Trastuzumab will be given intravenously (IV) at a dose of 6 mg/kg or subcutaneously (SC) at a fixed dose of 600 mg, once every 21 days.

AND

  • Pertuzumab will be given IV at 420 mg every 21 days. OR
  • Fixed dose combination of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given SC, once every 21 days, in lieu of trastuzumab and pertuzumab individually.

Study Type

Interventional

Enrollment (Actual)

654

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Macquarie University, New South Wales, Australia, 2109
        • Macquarie University Clinical Trials Unit.
      • Westmead, New South Wales, Australia, 2145
        • Western Sydney Local Health District (WSLHD), Westmead Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Cancer Research SA
      • Adelaide, South Australia, Australia, 5000
        • St Andrews Medical Centre
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
    • Washington
      • Subiaco, Washington, Australia, 6008
        • St John of God Subiaco Hospital Clinical Trials Unit Bendat Family Comprehensive Cancer Centre
  • Austria
      • Graz, Austria, A-8036
        • Medizinische Universität Graz
      • Graz, Austria, A-8010
        • Medizinische Universität Graz
      • Linz, Austria, A-4010
        • Ordensklinikum Linz GmbH Barmherzige Schwestern
      • Vienna, Austria, A-1090
        • Medizinische Universitat Wien Universitatsklinik Fur Frauenheilkunde
    • Other
      • Schwaz, Other, Austria, A-6130
        • Ordination Priv.-Doz. Dr. Michael Hubalek
  • Belgium
      • Anderlecht, Belgium, 1070
        • Jules Bordet lnstituut
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
      • Brussels, Belgium, 1090
        • Universitair Ziekenhuis Brussel (UZ Brussel)
      • Ottignies, Belgium, 1340
        • Clinique St-Pierre
  • Brazil
      • Porto Alegre/RS, Brazil, 90050-170
        • Irmandade da Santa Casa de Misericordia de Porto Alegre centro Multidisciplinar de pesquisa clinica
      • São José do Rio Preto, Brazil, 15090-000
        • Faculdade Regional de Medicina de Sao Jose do Rio Preto
      • São Paulo, Brazil, 04014-002
        • Sao Camilo Oncologia
      • São Paulo, Brazil, 01246-000
        • ICESP- Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira
      • São Paulo, Brazil, CEP: 01317-000
        • Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecologica e Mamária Ltda.
    • Ceará
      • Fortaleza, Ceará, Brazil, 60336-232
        • CRIO - Centro Regional lntegrado de Oncologia
    • Goiás
      • Goiânia, Goiás, Brazil, 74605-070
        • Hospital Araujo Jorge
    • Other
      • Sao Paulo/SP, Other, Brazil, 01.509-010
        • A.C. Camargo Câncer Center
    • Paraná
      • Londrina, Paraná, Brazil, 86015-520
        • Hospital do Cancer de Londrina
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59075-740
        • Liga Norte-Rio Grandense Contra o Cancer
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
        • Hospital De Clinicas De Porto Alegre
      • Porto Alegre, Rio Grande do Sul, Brazil, CEP 90110-270
        • Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital do Cancer Mae de Deu
      • Porto Alegre, Rio Grande do Sul, Brazil, CEP 90850-170
        • Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital do Cancer Mae de Deu
    • São Paulo
      • Barretos, São Paulo, Brazil, CEP: 14784-400
        • Fundacao Pio XII, Hospital do Amor de Barretos
      • Jaú, São Paulo, Brazil, CEP: 17210-080
        • Fundacao Dr Amaral Carvalho
      • Santo André, São Paulo, Brazil, 09060-650
        • CEPHO- Centro de Estudos e Pesquisas de Hematologia e Oncologia
      • Santo André, São Paulo, Brazil, 09060-870
        • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • BC Cancer Agency
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 5H6
        • Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H2X 3E4
        • Centre Hospitalier de l'Universite de Motreal (CHUM)
  • Chile
      • Talca, Chile, 3460000
        • Clinica Universidad Catolica del Maule
      • Temuco, Chile, 4810469
        • James Lind Centro de Investigacion del Cancer
      • Temuco, Chile, 4810297
        • Clinica Alemana Temuco
    • Santiago Metropolitan
      • Recoleta, Santiago Metropolitan, Chile, 8420323
        • Centro de Investigacion Clinica Bradford Hill
    • Valparaiso
      • Viña del Mar, Valparaiso, Chile
        • Oncocentro Apys
  • China
      • Beijing, China, 100730
        • Beijing Hospital
      • Beijing, China, 100010
        • Beijing Hospital
      • Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center
      • Tianjin, China, 300181
        • Tianjin Cancer Hospital Binhai Campus
    • Anhui
      • Hefei, Anhui, China, 230601
        • The Second Hospital of Anhui Medical University
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Guangdong Provincial People's Hospital
      • Meizhou, Guangdong, China, 514031
        • Meizhou People's hospital
    • Guangxi
      • Liuchow, Guangxi, China, 545006
        • Liuzhou people's Hospital
      • Nanning, Guangxi, China, 530021
        • The People's Hospital of Guangxi Zhuang Autonomous Region
      • Nanning, Guangxi, China, 530021
        • Guangxi Medical University Affiliated Tumor Hospital
    • Hainan
      • Haikou, Hainan, China, 570102
        • The First Affiliated Hospital of Hainan Medical University
    • Hebei
      • Baoding, Hebei, China, 071000
        • Affiliated Hospital of Hebei University
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Henan Cancer Hospital
    • Hubei
      • Wuhan, Hubei, China, 430079
        • Hubei Cancer Hospital
      • Wuhan, Hubei, China, 430030
        • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
    • Hunan
      • Changsha, Hunan, China, 410011
        • The second Xiangya Hospital of Central South University
    • Jiangsu
      • Nanjing, Jiangsu, China, 210036
        • Nanjing Medical University (NMU) - Jiangsu Province Hospital
    • Jiangxi
      • Nanchang, Jiangxi, China, 330008
        • The Second Affiliated Hospital of Nanchang University
    • Jilin
      • Changchun, Jilin, China, 130021
        • The First Hospital of Jilin University
    • Liaoning
      • Shenyang, Liaoning, China, 110042
        • Liaoning Cancer Hospital & Insitute
      • Shenyang, Liaoning, China, 110167
        • The First Affiliated Hospital of China Medical University
    • Other
      • Shanghai, Other, China, 200025
        • Ruijin Hospital of Shanghai Jiaotong University School of Medicine
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • The First Affiliated Hospital of Xi'an Jiaotong University
      • Xi'an, Shaanxi, China, 710068
        • Shaanxi Provincial People's Hospital
    • Shandong
      • Jinan, Shandong, China, 250013
        • Jinan Central Hospital
      • Linyi, Shandong, China, 276034
        • Linyi Cancer Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310016
        • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Hangzhou, Zhejiang, China, 310005
        • Zhejiang Cancer Hospital
      • Hangzhou, Zhejiang, China, 310052
        • The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Czechia
      • Brno, Czechia, 656 53
        • Masarykuv onkologicky ustav
      • Prague, Czechia, 128 08
        • Všeobecná fakultní nemocnice v Praze
      • Praha 5 - Motol, Czechia, 15006
        • Fakultni nemocnice v Motole Onkologicka klinika 2. LF UK a FN Motol
      • Praha 5 - Motol, Czechia, 15006
        • Nemocnicni lekarna Fakultni nemocnice v Motole
    • Other
      • Brno, Other, Czechia, 656 53
        • Ustavni lekarna Masarykuv onkologicky ustav
      • Praha 4 - Krc, Other, Czechia, 14059
        • Fakultni Thomayerova nemocnice Onkologicka klinika 1. LF UK a FTN
  • Finland
      • Tampere, Finland
        • Tampere University Hospital
      • Tampere, Finland, 33520
        • Tampere University Hospital, FONK/RSYO
  • France
      • Besançon, France, 25000
        • CHU Besançon
      • Bobigny, France, 93009 Cedex
        • Hôpital Avicenne
      • Caen, France, 14076 Cedex 5
        • CENTRE FRANCOIS BACLESSE - Service lmagerie medicale
      • Caen, France, 14076
        • Centre de Lutte contre le Cancer - François Baclesse
      • Caen, France, 14076 Cedex 5
        • Centre François Baclesse
      • Clermont-Ferrand, France, 63000
        • Centre Jean Perrin
      • Lille, France, 59020 Cedex
        • Centre Oscar Lambret
      • Lyon, France, 69373 Cedex 08
        • Center Leon Berard
      • Montpellier, France, 34298
        • Institut Regional du Cancer de Montpellier
      • Montpellier, France, 34298 Cedex 5
        • Institut Regional du Cancer de Montpellier Service lmagerie medicale
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Pierre-Bénite, France, 69310
        • Hospices Civils de Lyon
      • Plérin, France, 22190
        • "CARIO - Centre Armoricain de Radiotherapie lmagerie medicate et d'Oncologie -Hopital Prive des
      • Rennes, France, cedex 35042
        • Centre Eugene Marquis
      • Rouen, France, 76038 Cedex 1
        • Centre Henri Becquerel
      • Saint-Cloud, France, 92210
        • Institut Curie - site St-Cloud
      • Strasbourg, France, 67033
        • Centre de Lutte contre le Cancer Paul Strauss - CPS
    • Brittany Region
      • Rouen, Brittany Region, France, 76038
        • Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer
    • Cedex
      • Bordeaux, Cedex, France, 33076
        • Institut Bergonie
    • Languedoc-roussillon
      • Montpellier, Languedoc-roussillon, France, 34070
        • Centre de Cancerologie du Grand Montpellier
    • Loire-atlantique
      • Saint-Herblain, Loire-atlantique, France, 44800
        • Institut de Cancerologie de lOuest - Site Rene Gauducheau
      • Saint-Herblain, Loire-atlantique, France, 44805
        • Institut de Cancerologie de lOuest-Saint Herblain
    • Other
      • Avignon, Other, France, 84918
        • Institut Sainte-Catherine.
      • Avignon, Other, France, 84918
        • Sainte Catherine lnstitut du Cancer Avignon Provence
      • Dijon, Other, France, 21079
        • Center Georges-Francois Leclerc
  • Germany
      • Augsburg, Germany, 86156
        • "Universitatsklinikum Augsburg Klinik fur Frauenheilkunde und Geburtshilfe"
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin Berlin
      • Berlin, Germany, 10117
        • Charite Universtitatsmedizin Berlin Klinik fur Gynakologie mit Brustzentrum
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf (UKE)
      • München, Germany, 81675
        • Klinik und Poliklinik fur Frauenheilkunde der Technischen Universitat Munchen
      • Ulm, Germany, 89075
        • Universitatsklinikum Ulm Klinik fur Frauenheilkunde und Geburtshilfe
      • Würzburg, Germany, 97080
        • Universitatsklinikum Wurzburg Frauenklinik und Poliklinik
      • Würzburg, Germany, 97080
        • Universitatsklinikum Wurzburg, Comprehensive Cancer Center - Mainfranken (CCCMF)
    • North Rhine-Westphalia
      • Münster, North Rhine-Westphalia, Germany, 48149
        • University Hospital Muenster Senology
    • Other
      • Manheim, Other, Germany, 68167
        • Universitätsmedizin Mannheim Universitätsfrauenklinik
      • Mannheim, Other, Germany, 68167
        • Pharmacy:Fortuna Herstellung GmbH
  • Greece
      • Larissa, Greece, 41110
        • University General Hospital of Larissa, Oncology Clinic
      • Marousi, Greece, 15123
        • IASO General Clinic Oncology Clinic
      • Pireaus, Greece, 18537
        • Metaxa Anticancer Hospital of Piraeus
    • Attica
      • Athens, Attica, Greece, 11528
        • General Hospital of Athens "Alexandra" Clinical Therapeutics Department, Hematology/Oncology Unit
    • Peloponnese
      • Patra, Peloponnese, Greece, 26504
        • University General Hospital of Patras, Oncology Department, Internal Medicine Clinic
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
      • Bologna, Italy, 40138
        • SSD Oncologia Medica Addarii - Zamagni, Policlinico Sant'Orsola - Malpighi
      • Milan, Italy, 20089
        • Istituto Clinico Humanitas
      • Milan, Italy, 20141
        • Divisione di Senologia Medica; Istituto Europeo di Oncologia
      • Parma, Italy, 43126
        • UOC di Oncologia Medica, Azienda Ospedaliero Universitaria (AOU) di Parma
      • Pavia, Italy, 27100
        • Istituti Clinici Scientifici Maugeri IRCCS
    • Campania
      • Naples, Campania, Italy, 80131
        • Azienda Ospedaliera Universitaria Federico II
      • Naples, Campania, Italy, 80131
        • lstituto Nazionale Tumori IRCCS - Fondazione Pascale U.O.C. Oncologia Medica Senologica
    • Genoa
      • Genova, Genoa, Italy, 16132
        • IRCCS Azienda Ospedaliera Metropolitana
    • Lombardy
      • Monza (MB), Lombardy, Italy, 20900
        • ASST Monza Ospedale San Gerardo Centro Ricerca di Fase 1
    • Sicily
      • Catania (CT), Sicily, Italy, 95045
        • Humanitas lstituto Clinico Catanese
    • The Marches
      • Torrette, The Marches, Italy, 60126
        • Azienda Ospedaliero Universitaria delle Marche SOD Clinica Oncologica
    • Trentino-Alto Adige
      • Trento, Trentino-Alto Adige, Italy, 38122
        • Divisione Oncologia Medica, Ospedale di Trento - Presidio Ospedaliero (PO) Santa Chiara
      • Trento, Trentino-Alto Adige, Italy, 38122
        • SOC Farmacia, Ospedale di Trento - Presidio Ospedaliero (PO)
    • Tuscany
      • Livorno, Tuscany, Italy, 57124
        • Oncologia Medica Azienda Usl Toscana Nord Ovest - Ospedali Riuniti di Livor
      • Prato, Tuscany, Italy, 59100
        • S.O.C. Oncologia Medica - Nuovo Ospedale di Prato Santo Stefano
  • Japan
    • Chiba
      • Kamogawa, Chiba, Japan, 296-8602
        • Tesshokai Kameda General Hospital
      • Kashiwa-Shi, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Ehime
      • Matsuyama, Ehime, Japan, 791-0280
        • NHO Shikoku Cancer Center
    • Fukuoka
      • Fukuoka, Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center
    • Fukushima
      • Fukushima, Fukushima, Japan, 960-1295
        • Fukushima Medical University Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 003-0804
        • National Hospital Organization Hokkaido Cancer Center
    • Ibaraki
      • Tsukuba, Ibaraki, Japan, 305-8576
        • University of Tsukuba Hospital
    • Ishikawa-ken
      • Kanazawa, Ishikawa-ken, Japan, 920-8530
        • Ishikawa Prefectural Central Hospital
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 241-8515
        • Kanagawa Cancer Center
    • Okinawa
      • Naha, Okinawa, Japan, 901-0154
        • Naha Nishi Clinic
    • Osaka
      • Osakasayama-shi, Osaka, Japan, 589-8511
        • Kindai University Hospital
      • Sakai, Osaka, Japan, 590-0197
        • Kindai University Hospital
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Chuo-ku, Tokyo, Japan, 104-8560
        • St. Luke's International Hospital.
      • Minato-ku, Tokyo, Japan, 105-8470
        • Toranomon Hospital
      • Shinagawa-ku, Tokyo, Japan, 142-8666
        • Showa University Hospital
  • Netherlands
      • Dordrecht, Netherlands, 3318 AT
        • Albert Schweitzer Ziekenhuis
      • Utrecht, Netherlands, 3543 AZ
        • St. Antonius Hospital
      • Venlo, Netherlands, 5912 BL
        • VieCuri Medsich Centrum
    • South Holland
      • Doedrecht, South Holland, Netherlands, 3318AT
        • Albert Schweitzer Hospital
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne
      • Lodz, Poland, 91-211
        • Salve Medica
      • Lodz, Poland, 91-211
        • Salve Medica Apteka Szpitalna
      • Opole, Poland, 45-061
        • SP ZOZ Opolskie Centrum Onkologii im. prof. Tadeusza Koszarowskiego w Opolu
    • Other
      • Lodz, Other, Poland, 93-513
        • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
    • Silesian Voivodeship
      • Gliwice, Silesian Voivodeship, Poland, 44-102
        • Narodowy lnstytut Onkologii im. Marii Sklodowskiej-Curie-Panstwowy lnstytut Badawczy
  • Portugal
      • Coimbra, Portugal, 3000-075
        • Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE (IPO, Coimbra)
      • Lisbon, Portugal, 1400-038
        • Fundacao Champalimaud
    • Other
      • Braga, Other, Portugal, 4710-243
        • Centro Clinico Academico Braga Hospital de Braga
      • Lisbon, Other, Portugal, 1998-018
        • Hospital CUF Descobertas
  • South Korea
      • Busan, South Korea, 49201
        • Dong-A University Hospital
      • Incheon, South Korea, 21565
        • Gachon University Gil Medical Center
      • Seoul, South Korea, 02841
        • Korea University Anam Hospital
    • Gangwon-do
      • Wŏnju, Gangwon-do, South Korea, 26426
        • Yonsei University Wonju Severance Christian Hospital
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, South Korea, 10408
        • National Cancer Center
      • Seongnam-si, Gyeonggi-do, South Korea, 13620
        • Seoul National University Bundang Hospital
      • Suwon, Gyeonggi-do, South Korea, 16499
        • Ajou University Hospital
      • Suwon, Gyeonggi-do, South Korea, 16247
        • The Catholic university of Korea, St. Vincent's Hospital
    • North Chungcheong
      • Cheongju-si, North Chungcheong, South Korea, 28644
        • Chungbuk Nationl University Hospital
    • Other
      • Seoul, Other, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, Other, South Korea, 05505
        • Asan Medical Center
      • Seoul, Other, South Korea, 06273
        • Gangnam Severance Hospital, Yonsei University Health System
      • Seoul, Other, South Korea, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Other, South Korea, 07985
        • Ewha Womans University Mokdong Hospital
    • Seoul-teukbyeolsi [seoul]
      • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03722
        • Severance Hospital Yonsei University Health System
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08035
        • Fundació Hospital Universitari Vall d'Hebron - Institut de Recerca
      • Barcelona, Spain, 08025
        • Fundacio de Gestio Sanitaria de I'Hospital de la Santa Creu i Sant Pau
      • Bilbao, Spain, 48013
        • Hospital Universitario de Basurto
      • Girona, Spain, 17007
        • Institut Català d'Oncologia Girona - ICO Girona
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves
      • Lleida, Spain, 25198
        • Hospital Universitari Arnau de Vilanova
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca (Spain Salamanca)
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46009
        • Fundacion lnstituto Valenciano de Oncologia
    • Andalusia
      • Málaga, Andalusia, Spain, 29016
        • Hospital El Angel Grupo Hla, S.L.U
    • Balearic Islands
      • Palma de Mallorca, Balearic Islands, Spain, 07120
        • Hospital Universitario Son Espases
    • Murcia
      • EI Palmar, Murcia, Spain, 30120
        • Hospital Universitario Virgen de La Arrixaca
    • Other
      • Barcelona, Other, Spain, 08035
        • Fundación Privada Instituto de Investigación Oncológica de Vall Hebron
      • Cáceres, Other, Spain, 10003
        • Hospital San Pedro De Alcantara
      • Madrid, Other, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Valencia, Other, Spain, 46010
        • Hospital Clinico Universitario de Valencia
    • Santa CRUZ DE Tenerife
      • La Laguna Tenerife, Santa CRUZ DE Tenerife, Spain, 38320
        • Hospital Universitario de Canarias
    • Valencia
      • Alicante, Valencia, Spain, 03010
        • Hospital General Universitario Alicante
  • Switzerland
      • Baden, Switzerland, 5404
        • Kantonsspital Baden.
      • Zurich, Switzerland, 8008
        • Brust-Zentrum AG
    • Canton of Zurich
      • Winterthur, Canton of Zurich, Switzerland, 8401
        • Kantonsspital Winterthur
  • Taiwan
      • Changhua, Taiwan, 500 (R.O.C.)
        • Changhua Christian Medical Foundation Changhua Christian Hospital
      • Kaohsiung City, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • New Taipei City, Taiwan, 23561 (R.O.C.)
        • Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare
      • New Taipei City, Taiwan, 23561 (R.O.C)
        • Taipei Medical University - Shuang Ho Hospital, Ministry of Health and Welfare
      • Taichung, Taiwan, 40447 (R.O.C.)
        • China Medical University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Taipei, Taiwan, 11490, R.O.C.
        • Tri-Service General Hospital
      • Taoyuan, Taiwan, 333
        • Chang Gung Memorial Hospital LinKou
    • Other
      • Tainan, Other, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Other, Taiwan, 10449
        • MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital
      • Taipei, Other, Taiwan, 112
        • Koo Foundation Sun Yat-Sen Cancer Center
    • R.o.c
      • Taipei, R.o.c, Taiwan, 100
        • National Taiwan University Hospital
    • Tainan
      • Tainan, Tainan, Taiwan, 710
        • Chi Mei Medical Center
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden
      • London, United Kingdom, N12 0JE
        • Finchley Memorial Hospital
      • London, United Kingdom, NW1 2PG
        • University College London Hospital (UCLH) NHS Foundation Trust
      • Manchester, United Kingdom, M20 4BX
        • Christie Hospital NHS Foundation Trust
    • England
      • London, England, United Kingdom, NW3 2QG
        • Academic Oncology
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • The Royal Marsden
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Central Arkansas Radiation Therapy Institute Inc d.b.a CARTI
    • California
      • Beverly Hills, California, United States, 90212
        • UCLA Hematology/Oncology - Beverly Hills
      • Burbank, California, United States, 91505
        • UCLA Hematology/Oncology - Burbank
      • Encinitas, California, United States, 92024
        • UCSD Medical Center - Encinitas
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • La Jolla, California, United States, 92037
        • Sulpizio Cardiovascular Center at UC San Diego Health
      • La Jolla, California, United States, 92037
        • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
      • La Jolla, California, United States, 92037
        • UCSD Perlman Medical Offices
      • La Jolla, California, United States, 92037
        • UCSD Koman Family Outpatient Pavilion
      • Laguna Hills, California, United States, 92653
        • UCLA Hematology/Oncology - Laguna Hills
      • Los Angeles, California, United States, 90095
        • UCLA Hematology/Oncology
      • Los Angeles, California, United States, 90095
        • Administrative Address: UCLA Hematology/Oncology
      • San Diego, California, United States, 92103
        • UC San Diego Medical Center - Hillcrest
      • San Diego, California, United States, 912101
        • UCSD Medical Center - Bankers Hill
      • San Luis Obispo, California, United States, 93401
        • UCLA Hematology/Oncology - San Luis Obispo
      • Santa Barbara, California, United States, 93101
        • UCLA Hematology/Oncology- Santa Barbara
      • Santa Monica, California, United States, 90404
        • UCLA Hematology/Oncology - Santa Monica
      • Santa Monica, California, United States, 90404
        • UCLA Hematology/Oncology Parkside
      • Torrance, California, United States, 90509
        • Harbor-UCLA Medical Center
      • Torrance, California, United States, 90502
        • The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
      • Torrance, California, United States, 90502
        • Clinical And Translational Research Center
      • Valencia, California, United States, 91355
        • UCLA Hematology/Oncology - Santa Clarita
      • Vista, California, United States, 92081
        • UCSD Medical Center - Vista
      • Westlake Village, California, United States, 91361
        • UCLA Hematology/Oncology- Westlake
    • Florida
      • Altamonte Springs, Florida, United States, 32701
        • AdventHealth Altamonte Infusion Center
      • Altamonte Springs, Florida, United States, 32701
        • AdventHealth Medical Group Altamonte(second location)
      • Altamonte Springs, Florida, United States, 32701
        • AdventHealth Medical Group Altamonte
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Florida
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando Infusion Center
      • Orlando, Florida, United States, 32804
        • AdventHealth Medical Group Orlando
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute
      • Atlanta, Georgia, United States, 30322
        • Emory University Clinic
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Hospital and Health Systems
      • Chicago, Illinois, United States, 60612
        • University of Illinois Hospital and Health Systems (Outpatient Cancer Center)
      • Chicago, Illinois, United States, 60612
        • University of Illinois Hospital and Health Systems (Investigational Drug Pharmacy)
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Norton Cancer Institute, St. Matthews Campus
      • Louisville, Kentucky, United States, 40207
        • Norton Cancer Institute, St Matthews Campus
      • Louisville, Kentucky, United States, 40241
        • Norton Cancer Institute, Brownsboro Hospital Campus
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute, Downtown
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute - Downtown
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Cancer Institute.
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • Oncology Hematology West, PC dba Nebraska Cancer Specialists - Grand Island
      • Grand Island, Nebraska, United States, 68803
        • Oncology Hematology West PC dba Nebraska Cancer Specialists
      • Omaha, Nebraska, United States, 68130
        • Oncology Hematology West PC dba Nebraska Cancer Specialists
      • Omaha, Nebraska, United States, 68124
        • Oncology Hematology West PC dba Nebraska Cancer Specialists
      • Omaha, Nebraska, United States, 68114
        • Oncology Hematology West PC dba Nebraska Cancer Specialists
      • Papillion, Nebraska, United States, 68046
        • Oncology Hematology West PC dba Nebraska Cancer Specialists
    • New Jersey
      • Jersey City, New Jersey, United States, 07302
        • RWJBarnabas Health- Jersey City Medical Center
      • Lakewood, New Jersey, United States, 08701
        • RWJBarnabas Health- Monmouth Medical Center-Southern Campus
      • Livingston, New Jersey, United States, 07039
        • RWJBarnabas Health- Cooperman Barnabas Medical Center
      • Long Branch, New Jersey, United States, 07740
        • RWJBarnabas Health- Monmouth Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Somerville, New Jersey, United States, 08876
        • Steeplechase Cancer Center
      • Somerville, New Jersey, United States, 08876
        • RWJBarnabas Health-Robert Wood Johnson University Hospital, Somerset
      • Toms River, New Jersey, United States, 08755
        • RWJBarnabas Health - Community Medical Center
      • West Long Branch, New Jersey, United States, 07764
        • Satellite Infusion Center-Monmouth Medical Center Vantage Point Infusion Center
    • New York
      • The Bronx, New York, United States, 10461
        • Montefiore Einstein Comprehensive Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
      • Strongsville, Ohio, United States, 44136
        • Cleveland Clinic Cancer Center - Strongsville
    • Pennsylvania
      • Willow Grove, Pennsylvania, United States, 19090
        • Asplundh Cancer Pavillion
    • Tennessee
      • Gallatin, Tennessee, United States, 37066
        • Tennessee Oncology, PLLC
      • Murfreesboro, Tennessee, United States, 37129
        • Tennessee Oncology, PLLC
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute- Pharmacy
      • Shelbyville, Tennessee, United States, 37160
        • Tennessee Oncology, PLLC
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital/Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).

  • Have unresectable locally advanced or metastatic disease.

    • If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab and pertuzumab received in the early breast cancer setting for advanced HER2+ disease.
  • Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
  • Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

  • CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:

    • No evidence of brain metastases
    • Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane

    • Previously treated brain metastases which are asymptomatic

      • Brain metastases previously treated with local therapy must not have progressed since treatment

Exclusion Criteria:

  • Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
  • Unable to undergo contrast-enhanced MRI of the brain

  • CNS Exclusion - Based on screening brain MRI and clinical assessment

    • Symptomatic brain metastasis after CNS-directed local therapy
    • Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
    • Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent)
    • Any untreated brain lesion in an anatomic site which may pose risk to participant
    • Known or suspected leptomeningeal disease (LMD)
    • Poorly controlled (>1/week) seizures, or other persistent neurologic symptoms

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tucatinib + trastuzumab + pertuzumab
Drug: Tucatinib
300mg given by mouth (orally) twice daily
Other Names:
  • TUKYSA, ONT-380, ARRY-380
Drug: Trastuzumab
6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days
Other Names:
  • Herceptin, Herceptin Hylecta
Drug: Pertuzumab
420mg given by IV every 21 days
Other Names:
  • Perjeta
Drug: Combination product: Trastuzumab + Pertuzumab
600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.
Other Names:
  • Phesgo
Active Comparator: Placebo + trastuzumab + pertuzumab
Drug: Trastuzumab
6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days
Other Names:
  • Herceptin, Herceptin Hylecta
Drug: Pertuzumab
420mg given by IV every 21 days
Other Names:
  • Perjeta
Drug: Combination product: Trastuzumab + Pertuzumab
600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.
Other Names:
  • Phesgo
Drug: Placebo
Given orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to approximately 3 years
The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause
Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to approximately 5 years
The time from randomization to death from any cause.
Up to approximately 5 years
PFS by blinded independent central review (BICR) per RECIST v1.1
Time Frame: Up to approximately 3 years
The time from the date of randomization to the documented disease progression assessed by BICR according to RECIST v1.1 or death from any cause
Up to approximately 3 years
Time to deterioration of health-related quality of life (HRQoL)
Time Frame: Up to approximately 3 years
Will be measured based on patient reported outcomes (PROs) according to the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30).
Up to approximately 3 years
Central nervous system (CNS) PFS
Time Frame: Up to approximately 3 years
The time from randomization to investigator assessed disease progression in brain (RECIST v1.1), or death from any cause
Up to approximately 3 years
Incidence of adverse events (AEs)
Time Frame: Through 30 days after last study treatment, approximately 18 months
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Through 30 days after last study treatment, approximately 18 months
Incidence of laboratory abnormalities
Time Frame: Through 30 days after last study treatment, approximately 18 months
To be summarized using descriptive statistics.
Through 30 days after last study treatment, approximately 18 months
Incidence of tucatinib dose alterations
Time Frame: Through 30 days after last study treatment, approximately 18 months
To be summarized using descriptive statistics.
Through 30 days after last study treatment, approximately 18 months
Incidence of trastuzumab dose alterations
Time Frame: Through 30 days after last study treatment, approximately 18 months
To be summarized using descriptive statistics.
Through 30 days after last study treatment, approximately 18 months
Incidence of pertuzumab dose alterations
Time Frame: Through 30 days after last study treatment, approximately 18 months
To be summarized using descriptive statistics.
Through 30 days after last study treatment, approximately 18 months
Maximum concentration (Cmax)
Time Frame: Through 30 days after last study treatment, approximately 18 months
To be summarized using descriptive statistics.
Through 30 days after last study treatment, approximately 18 months
Trough concentration (Ctrough)
Time Frame: Through 30 days after last study treatment, approximately 18 months
To be summarized using descriptive statistics.
Through 30 days after last study treatment, approximately 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seagen, a wholly owned subsidiary of Pfizer

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2022

Primary Completion (Actual)

September 5, 2025

Study Completion (Estimated)

September 28, 2027

Study Registration Dates

First Submitted

November 12, 2021

First Submitted That Met QC Criteria

November 12, 2021

First Posted (Actual)

November 24, 2021

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 17, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGNTUC-028
  • C4251007 (Other Identifier: Alias Study Number)
  • 2023-503826-37-00 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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