Brief 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.

Conditions

• HER2 Positive Breast Cancer

Intervention / Treatment

• Drug: Tucatinib
• Drug: Trastuzumab
• Drug: Trastuzumab
• Drug: Pertuzumab
• Drug: Pertuzumab
• Drug: Combination product: Trastuzumab + Pertuzumab
• Drug: Combination product: Trastuzumab + Pertuzumab
• Drug: Placebo

Primary Outcome Measures

• Progression-Free Survival (PFS) as Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 (From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months))
  PFS: time from randomization to the first documented disease progression (PD) (as assessed by investigator per RECIST 1.1) or death from any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum of diameter recorded since the treatment started or the appearance of 1 or more new lesions. Participants without documentation of PD/ death at the time of analysis, were censored at date of last tumor assessment with an overall response of complete response (CR), partial response (PR), stable disease (SD), non-CR/non-PD or no evidence of disease (NED). CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameter since the treatment started. Kaplan-Meier method was used for analysis.

Countries

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

Locations and Investigators

• Cliniques Universitaires Saint-Luc, Sint-Lambrechts-Woluwe, Belgium
  • François, Duhoux
• Institut Jules Bordet, Anderlecht, Belgium
  • Michail, Ignatiadis
• Clinique Saint-Pierre, Ottignies-Louvain-La-Neuve, Belgium
  • Renaud, Poncin
• University Of Helsinki, Helsinki, Finland
  • Johanna, Mattson
• Tampere University Hospital, Tampere, Finland
  • Minna, Tanner
• Kuopio University Hospital, Kuopio, Finland
  • Paivi, Auvinen
• Vaasa Central Hospital, Vaasa, Finland
  • Antti, Jekunen
• Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico, Bologna, Italy
  • Claudio, Zamagni
• Humanitas Research Hospital, Rozzano, Italy
  • Armando, Santoro
• Azienda Ospedaliera Universitaria Federico II Di Napoli, Naples, Italy
  • Grazia, Arpino
• Azienda Ospedaliero Universitaria Delle Marche, Ancona, Italy
  • Rossana, Berardi
• IRCCS Ospedale Policlinico San Martino, Genoa, Italy
  • Lucia, Del Mastro
• Humanitas Istituto Clinico Catanese S.p.A., Misterbianco, Italy
  • Michele, Caruso
• Azienda Provinciale Per I Servizi Sanitari, Trento, Italy
  • Antonella, Ferro
• Istituto Europeo Di Oncologia S.r.l., Milan, Italy
  • Marco, Colleoni
• Istituti Clinici Scientifici Maugeri In Forma Abbreviata Istituti Clinici Scientifici Maugeri O Anche Ics Maugeri O Maugeri S.p.A. Sb, Pavia, Italy
  • Laura, Locati
• Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy
  • Marina, Cazzaniga
• IRCCS Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
  • Michelino, De Laurentiis
• Universita' Degli Studi Di Ferrara, Ferrara, Italy
  • Alessio, Schirone
• Azienda Unita Sanitaria Locale Toscana Nord Ovest, Leghorn, Italy
  • Luigi, Coltelli
• University Of Parma, Parma, Italy
  • Daniela, Boggiani
• Azienda USL Toscana Centro, Prato, Italy
  • Laura, Biganzoli
• Metaxa Cancer Center Hospital Of Piraeus, Pireas, Greece
  • Christos, Kosmas
• Alexandra Hospital, Athens, Greece
  • Flora, Zagouri
• General University Hospital Of Larissa, Larissa, Greece
  • Athanasios, Kotsakis
• Iaso Private General Obstetrics Gynecological & Pediatric Clinic Diagnostic Therapeutic & Research Center S.A., Filothei, Greece
  • Sophia, Karageorgopoulou
• General University Hospital Of Patras, Patras, Greece
  • Angelos, Koutras
• Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy, Gliwice, Poland
  • Michal, Jarzab
• Uniwersyteckie Centrum Kliniczne, Gdansk, Poland
  • Jacek, Jassem
• Opolskie Centrum Onkologii Im. Prof. Tadeusza Koszarowskiego W Opolu Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Opole, Poland
  • Barbara, Radecka
• Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi, Lodz, Poland
  • Monika, Rys-Bednarska
• Ordination PD Dr. M. Hubalek, Schwaz, Austria
  • Michael, Hubalek
• Medical University Of Graz, Graz, Austria
  • Vassiliki, Kolovetsiou-Kreiner
• Medical University Of Vienna, Vienna, Austria
  • Christian, Singer
• Ordensklinikum Linz GmbH, Linz, Austria
  • Andreas, Reichinger
• Institut Catala D'oncologia, Girona, Spain
  • Sonia, Del Barco
• University Hospital Son Espases, Palma, Spain
  • Neus, Ferrer Tur
• University Hospital Virgen Del Rocio S.L., Sevilla, Spain
  • Manuel, Ruiz Borrego
• Hospital General Universitario Dr. Balmis, Alicante, Spain
  • Jose, Ponce Lorenzo
• Hospital Universitari Vall D Hebron, Barcelona, Spain
  • Santiago, Escriva de Romani Munoz
• Hospital Clinico Universitario De Valencia, Valencia, Spain
  • Begona, Bermejo
• Hospital Universitario De Salamanca, Salamanca, Spain
  • Cesar, Rodriguez Sanchez
• Hospital Universitario Virgen De Las Nieves, Granada, Spain
  • Encarnacion, Gonzalez Flores
• Fundacion Instituto Valenciano De Oncologia, Valencia, Spain
  • Joaquin, Gavila Gregori
• Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida, Lleida, Spain
  • Serafin, Morales Murillo
• Hospital Universitario Virgen De La Victoria, Malaga, Spain
  • Maria Emilia, Dominguez Recio
• Hospital De La Santa Creu I Sant Pau, Barcelona, Spain
  • Pablo Rene, Rivera Vargas
• Hospital San Pedro De Alcantara, Caceres, Spain
  • Santiago, Gonzalez Santiago
• Hospital Universitario De Canarias, La Laguna, Spain
  • Josefina, Cruz Jurado
• Hospital Universitario Ramon Y Cajal, Madrid, Spain
  • Elena, Lopez Miranda

And 43 other sites.

Study Officials

• Pfizer CT.gov Call Center (Study Director) — Pfizer