A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer

HER2 Positive Breast Cancer Clinical Trial

— HER2CLIMB-05  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05132582
• Other study ID #: SGNTUC-028
• Status: Recruiting
• Phase: Phase 3
• Start date: March 7, 2022
• Est. completion date: June 30, 2027

Study information

• Verified date: June 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 650
• Est. completion date: June 30, 2027
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2 Positive Breast Cancer

Intervention

Drug:
• Tucatinib
300mg given by mouth (orally) twice daily
• Trastuzumab
6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days
• Pertuzumab
420mg given by IV every 21 days
• 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.
• Placebo
Given orally twice daily

Locations

Country	Name	City	State
Australia	Cancer Research South Australia	Adelaide	Other
Australia	Flinders Medical Centre	Bedford Park	Other
Australia	Box Hill Hospital	Box Hill	Other
Australia	Chris O'Brien Lifehouse	Camperdown	Other
Australia	Peninsula and South East Oncology	Frankston	Other
Australia	Austin Health	Heidelberg	Other
Australia	Macquarie University Hospital	Macquarie University	Other
Australia	St John of God Subiaco Hospital	Subiaco	Other
Australia	Westmead Hospital	Sydney	Other
Austria	LKH- Universitat Klinikum Graz	Graz	Other
Austria	Medizinische Universitat Innsbruck	Innsbruck	Other
Austria	Ordensklinikum Linz GmbH Barmherzige Schwestern	Linz	Other
Austria	Ordination Priv.-Doz. Dr. M. Hubalek	Schwaz	Other
Austria	AKH - Medizinische Universitat Wien	Vienna	Other
Belgium	Institut Jules Bordet	Anderlecht	Other
Belgium	UCL Saint-Luc	Brussels	Other
Belgium	Universitair Ziekenhuis Brussel	Bruxelles-Capitale	Other
Belgium	Clinique Saint Pierre	Ottignies	Other
Belgium	GZA Hospital Sint-Augustinus	Wilrijk	Other
Brazil	Hospital de Cancer de Barretos - Fundacao Pio XII	Barretos	Other
Brazil	Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda.	Bela Vista	Other
Brazil	INCAN - Instituto do Cancer - Hospital Pompeia	Caxias do Sul	Other
Brazil	Centro Regional Integrado de Oncologia	Fortaleza	Other
Brazil	Hospital Araujo Jorge - Associacao de Combate ao Cancer em Goias	Goiania	Other
Brazil	Fundacao Doutor Amaral Carvalho	Jaú	Other
Brazil	Hospital do Cancer de Londrina	Londrina	Other
Brazil	Liga Norte-Rio-Grandense Contra o Cancer	Natal	Other
Brazil	Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa	Porto Alegre	Other
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Other
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	Other
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Other
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo Andre	Other
Brazil	Praxis Pesquisa Medica	Santo Andre	Other
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Jose Rio Preto	Other
Brazil	Fundacao Antonio Prudente (AC Camargo Cancer Center)	Sao Paulo	Other
Brazil	Sao Camilo Oncologia	Sao Paulo	Other
Brazil	ICESP - Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira	São Paulo	Other
Canada	CIUSSS du Saguenay Lac Saint Jean	Chicoutimi	Quebec
Canada	University of Alberta / Cross Cancer Institute	Edmonton	Alberta
Canada	BC Cancer Kelowna	Kelowna	British Columbia
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Chile	Centro de Investigacion Clinica Bradford Hill	Santiago	Other
Chile	Pontificia Universidad Catolica De Chile Santiago	Santiago	Other
Chile	Clinica Universidad Catolica del Maule	Talca	Other
Chile	Sociedad de Investigaciones Medicas Limitada	Temuco	Other
Chile	Oncocentro APYS	Viña del Mar	Other
China	Affiliated Hospital of Hebei University	Baoding	Other
China	Beijing Hospital	Beijing	Other
China	The First Bethune Hospital of Jilin University	Changchun	Other
China	The Second Xiangya Hospital of Central South University	Changsha	Other
China	Affiliated Hospital of Chengde Medical University	Chengde	Other
China	The First People's Hospital of Foshan	Foshan	Other
China	900TH Hospital of Joint Logistics Support Force	Fuzhou	Other
China	Fujian Provincial Cancer Hospital	Fuzhou	Other
China	Guangdong Provincial People's Hospital	Guangzhou	Other
China	The first Affiliated Hospital of Hainan Medical University	Haikou	Other
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Other
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Other
China	Zhejiang Cancer Hospital	Hangzhou City	Other
China	Harbin Medical University Cancer Hospital	Harbin	Other
China	The Second Hospital of Anhui Medical University	Hefei	Other
China	The Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Other
China	Jinan Central Hospital	Jinan	Other
China	Linyi Cancer Hospital	Linyi	Other
China	Liuzhou People's Hospital	Liuzhou	Other
China	Meizhou People's Hospital - Guangdong Province	Meizhou	Other
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Other
China	Nanchang Third Hospital	Nanchang City
China	Nanjing Medical University (NMU) - Jiangsu Province Hospital	Nanjing	Other
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Other
China	Nantong Tumor Hospital	Nantong	Other
China	Fudan University Shanghai Cancer Center	Shanghai	Other
China	Ruijin Hospital of Shanghai Jiaotong University School of Medicine	Shanghai	Other
China	Liaoning Cancer Hospital and Institute	Shenyang	Other
China	The First Hospital of China Medical University	Shenyang	Other
China	Tianjin Medical University - Cancer Institute & Hospital	Tianjin	Other
China	Hubei Cancer Hospital	Wuhan	Other
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan City	Other
China	Shaanxi Provincial People's Hospital	Xi'an	Other
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Other
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang	Other
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Other
China	Xuzhou Central Hospital	Xuzhou	Other
China	Yantai Yuhuangding Hospital	Yantai	Other
China	Henan Cancer Hospital	Zhengzhou	Other
China	Henan Provincial People's Hospital	Zhengzhou	Other
Czechia	Masaryk Memorial Cancer Institute	Brno	Other
Czechia	Nemocnice Horovice (NH Hospital) a.s.	Praha	Other
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2	Other
Czechia	Thomayer University Hospital (Fakultní Thomayerova nemocnice)	Praha 4-Krc	Other
Czechia	Fakultni nemocnice v Motole	Praha 5	Other
Finland	Helsinki University Hospital	Helsinki	Other
Finland	Kuopio University Hospital	Kuopio	Other
Finland	Tampere University Hospital	Tampere, Pirkanmaa	Other
Finland	Vaasa Central Hospital	Vaasa	Other
France	Sainte Catherine Institut du Cancer Avignon Provence	Avignon	Other
France	Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz	Besancon Cedex	Other
France	Centre Hospitalier Universitaire Hopital Avicenne	Bobigny	Other
France	Institut Bergonie	Bordeaux	Other
France	Centre de Lutte contre le Cancer - Francois Baclesse	Caen Cedex 5	Other
France	Centre Jean Perrin	Clermont-Ferrand	Other
France	CARIO - Centre Armoricain De Radiothérapie, D'imagerie Médicale Et D'oncologie	Cotes d'Armor	Other
France	Center Georges Francois Leclerc	Dijon	Other
France	Centre de Lutte contre le Cancer (CLCC) - Centre Oscar Lambret	Lille	Other
France	Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren	Limoges Cedex	Other
France	Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes	Lyon cedex 08	Other
France	Centre de Cancerologie du Grand Montpellier	Montpellier	Other
France	Institut Regional du Cancer de Montpellier	Montpellier	Other
France	Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne	Nice Cedex 2	Other
France	Institut Curie	Paris
France	Hopitaux Civils de Lyon	Pierre Benite	Other
France	Centre Eugene Marquis	Rennes	Other
France	Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer	Rouen	Other
France	Institut de Cancerologie de lOuest - Site Rene Gauducheau	Saint Herblain cedex	Other
France	Institut Curie	Saint-Cloude	Other
France	Institut de cancerologie Strasbourg Europe	Strasbourg	Other
Germany	Universitatsklinikum Augsburg	Augsburg	Other
Germany	Charite Universitatsmedizin Berlin	Berlin	Other
Germany	Universitaetsklinikum Dusseldorf	Dusseldorf	Other
Germany	Universitatsklinikum Erlangen	Erlangen	Other
Germany	Universitaetsklinikum Essen	Essen	Other
Germany	Klinikum Esslingen GmbH	Esslingen	Other
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE)	Hamburg	Other
Germany	Medizinische Hochschule Hannover	Hannover	Other
Germany	St. Elisabeth-Krankenhaus Koln-Hohenlind	Koln	Other
Germany	Universitatsklinikum Schleswig-Holstein - Campus Lubeck	Lubeck	Other
Germany	Medical Faculty Mannheim, Heidelberg University	Mannheim	Other
Germany	Klinikum Rechts der Isar der Technischen Universitaet Muenchen	München	Other
Germany	Universitaetsklinikum Muenster	Münster	Other
Germany	Krankenhaus St. Josef	Regensburg
Germany	Universitatsklinik Tuebingen	Tubingen	Other
Germany	Universitatsklinikum Ulm	Ulm	Other
Germany	Uniklinikum Wurzburg	Wurzburg	Other
Greece	Alexandra General Hospital of Athens	Athens	Other
Greece	University Hospital Attikon	Haidari	Other
Greece	University General Hospital of Heraklion (PAGNI)	Heraklion	Other
Greece	University Hospital of Larissa	Larissa	Other
Greece	Hygeia Hospital	Marousi	Other
Greece	IASO	Maroussi	Other
Greece	General Hospital of Thessaloniki Papageorgiou	Nea Efkarpia	Other
Greece	Metropolitan General Hospital	Neo Faliro	Other
Greece	University Hospital of Patras	Patras	Other
Greece	Metaxa Anticancer Hospital of Piraeus	Pireaus	Other
Greece	Euromedica General Clinic	Thessaloniki	Other
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna	Other
Italy	Azienda Ospedaliero-Universitaria di Ferrara	Cona (FE)	Other
Italy	Azienda Ospedaliera Universitaria San Martino	Genova	Other
Italy	Azienda Usl Toscana Nord Ovest	Livorno	Other
Italy	Istituto Europeo di Oncologia	Milano	Other
Italy	Humanitas Istituto Clinico Catanese	Misterbianco (CT)	Other
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Other
Italy	Azienda Ospedaliera Universitaria (AOU) Federico II	Napoli	Other
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli	Other
Italy	Ospedale Sacro Cuore Don Calabria	Negrar Di Valpolicella	Other
Italy	Istituto Oncologico Veneto - IRCCS	Padova	Other
Italy	XX.Servizio Sanitario Regionale Emilia-Romagna Azienda Ospedaliero Universitaria di Parma	Parma	Other
Italy	IRCCS ICS Maugeri	Pavia	Other
Italy	Azienda USL 4 Prato - Ospedale Misericordia e Dolce di Prato	Prato	Other
Italy	Istituto Clinico Humanitas-Humanitas Cancer Center	Rozzano (Milano)	Other
Italy	A.O.U. - Ospedali Riuniti di Ancona	Torrette (AN)	Other
Italy	Azienda Provinciale per i Servizi Sanitari Provincia Autonoma di Trento - Presidio Ospedaliero S. Chiara	Trento	Other
Japan	National Cancer Center Hospital	Chuo-ku	Other
Japan	St. Luke's International Hospital	Chuo-ku	Other
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Other
Japan	Fukushima Medical University Hospital	Fukushima-shi	Other
Japan	University of Tsukuba Hospital	Ibaraki	Other
Japan	Tesshokai Kameda General Hospital	Kamogawa-shi	Other
Japan	Ishikawa Prefectural Central Hospital	Kanazawa-shi	Other
Japan	National Cancer Center Hospital East	Kashiwa-shi	Other
Japan	NHO Shikoku Cancer Center	Matsuyama	Other
Japan	Toranomon Hospital	Minato-ku	Other
Japan	Naha Nishi Clinic	Naha-shi	Other
Japan	Kindai University Hospital	Osakasayama-Shi	Other
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo-shi	Other
Japan	Showa University Hospital	Shinagawa-ku	Other
Japan	Kanagawa Cancer Center	Yokohama	Other
Korea, Republic of	Dong-A University Hospital	Busan	Other
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Other
Korea, Republic of	National Cancer Center	Goyang-si	Other
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Other
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Other
Korea, Republic of	Asan Medical Center	Seoul	Other
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul	Other
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul	Other
Korea, Republic of	Seoul National University Hospital	Seoul	Other
Korea, Republic of	Seoul Saint Mary's Hospital	Seoul	Other
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Other
Korea, Republic of	Ajou University Hospital	Suwon-si	Other
Korea, Republic of	St. Vincent's Hospital, The Catholic University of Korea	Suwon-si	Other
Korea, Republic of	Severance Hospital, Yonsei University Health System	Wonju-si	Other
Netherlands	Netherlands Cancer Institute	Amsterdam	Other
Netherlands	Albert Schweitzer Hospital	Doedrecht	Other
Netherlands	Medisch Centrum Leeuwarden (MCL)	Leeuwarden	Other
Netherlands	St. Antonius Hospital	Nieuwegein	Other
Netherlands	VieCuri Medisch Centrum	Venlo	Other
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Other
Poland	Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO)	Gliwice	Other
Poland	Przychodnia Lekarska KOMED Roman Karaszewski	Konin	Other
Poland	Salve Medica	Lodz	Other
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im.M.Kopernika w Lodzi	Lodz	Other
Poland	SP ZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego	Opole	Other
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa	Other
Portugal	Hospital de Braga	Braga	Other
Portugal	Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE (IPO, Coimbra)	Coimbra	Other
Portugal	Hospital Cuf Descobertas	Lisboa	Other
Portugal	Hospital Santa Maria	Lisboa	Other
Portugal	Champalimaud Clinical Center	Lisbon	Other
Portugal	Centro Hospitalar De Vila Nova De Gaia Espinho	Vila Nova de Gaia	Other
Spain	Hospital General Universitario Alicante	Alicante	Other
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Other
Spain	Hospital Del Mar	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	Hospital Universitario de Basurto	Bilbao	Other
Spain	Complejo Hospitalario De Caceres - Hospital General San Pedro De Alcantara	Caceres	Other
Spain	Institut Catala d'Oncologia Girona - ICO Girona	Girona	Other
Spain	Hospital Universitario Virgen de las Nieves	Granada	Other
Spain	Hospital Universitari Arnau de Vilanova	Lleida	Other
Spain	Hospital General Universitario Gregorio Maranon	Madrid	Other
Spain	Hospital Universitario Ramon y Cajal Servicio de Oncologia Medica Oficina de Ensayos Clinicos	Madrid	Other
Spain	Hospital Universitario Virgen de la Victoria	Malaga	Other
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia	Other
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Other
Spain	Hospital Clinico Universitario de Salamanca	Salamanca	Other
Spain	Hospital Universitario de Canarias	San Cristóbal de la Laguna	Other
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Other
Spain	Hospital Clinico Universitario de Valencia	Valencia	Other
Spain	Valencian Institute of Oncology Foundation	Valencia	Other
Switzerland	Kantonsspital Baden AG	Baden	Other
Switzerland	Kantonsspital Winterthur (KSW)	Winterthur	Other
Switzerland	Brust-Zentrum Zurich	Zurich	Other
Taiwan	Changhua Christian Hospital	Changhua	Other
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung	Other
Taiwan	Taipei Medical University Hospital	New Taipei City	Other
Taiwan	China Medical University Hospital	Taichung	Other
Taiwan	Chi Mei Hospital Liouying	Tainan	Other
Taiwan	National Cheng-Kung University Hospital	Tainan	Other
Taiwan	Central Hospital of the Ministry of National Defense	Taipei	Other
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Sun Yat-sen University Cancer Center	Taipei	Other
Taiwan	Taipei Veterans General Hospital	Taipei	Other
Taiwan	Mackay Memorial Hospital	Taipei City	Other
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan	Other
United Kingdom	The University of Edinburgh	Edinburgh	Other
United Kingdom	Royal Free London NHS Foundation Trust	London	Other
United Kingdom	The Royal Marsden NHS Foundation Trust (RM)	London	Other
United Kingdom	University College London Hospitals NHS Foundation Trust	London	Other
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester	Other
United Kingdom	The Royal Marsden NHS Foundation Trust (RM)	Sutton	Other
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Mercy Medical Center -Weinberg Center	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Charleston Oncology	Charleston	South Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	Zangmeister Cancer Center	Columbus	Ohio
United States	Nebraska Cancer Specialists	Grand Island	Nebraska
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Rutgers Cancer Institute of New Jersey	Jersey City	New Jersey
United States	Saint Luke's Cancer Institute LLC	Kansas City	Missouri
United States	UC San Diego / Moores Cancer Center	La Jolla	California
United States	Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	Saint Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Medical College of Wisconsin (Milwaukee)	Milwaukee	Wisconsin
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Oncology Hematology West, P.C.	Omaha	Nebraska
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	Orlando Health, Inc. TRIO	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	UCLA Department of Medicine - Hematology & Oncology	Santa Monica	California
United States	Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Community Medical Center	Toms River	New Jersey
United States	Lundquist Institute/Harbor-UCLA	Torrance	California
United States	Thomas Jefferson University	Willow Grove	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  Finland,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	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	Overall survival (OS)	The time from randomization to death from any cause.	Up to approximately 5 years
Secondary	PFS by blinded independent central review (BICR) per RECIST v1.1	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
Secondary	Time to deterioration of health-related quality of life (HRQoL)	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
Secondary	Central nervous system (CNS) PFS	The time from randomization to investigator assessed disease progression in brain (RECIST v1.1), or death from any cause	Up to approximately 3 years
Secondary	Incidence of adverse events (AEs)	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
Secondary	Incidence of laboratory abnormalities	To be summarized using descriptive statistics.	Through 30 days after last study treatment, approximately 18 months
Secondary	Incidence of tucatinib dose alterations	To be summarized using descriptive statistics.	Through 30 days after last study treatment, approximately 18 months
Secondary	Incidence of trastuzumab dose alterations	To be summarized using descriptive statistics.	Through 30 days after last study treatment, approximately 18 months
Secondary	Incidence of pertuzumab dose alterations	To be summarized using descriptive statistics.	Through 30 days after last study treatment, approximately 18 months
Secondary	Maximum concentration (Cmax)	To be summarized using descriptive statistics.	Through 30 days after last study treatment, approximately 18 months
Secondary	Trough concentration (Ctrough)	To be summarized using descriptive statistics.	Through 30 days after last study treatment, approximately 18 months