A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer (IMpassion050)
Breast Cancer

About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of HER2-positive breast cancer, and hormonal and PD-L1 status, as documented through central testing of a representative tumor tissue specimen
- Primary breast tumor size of > 2 cm by any radiographic measurement
- Stage at presentation: T2-T4, N1-N3, M0 as determined by AJCC staging system, 8th edition
- Pathologic confirmation of nodal involvement with malignancy must be determined by fine needle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not permitted.
- Patients with multifocal tumors are eligible provided at least one focus is sampled and centrally confirmed as HER2-positive.
- Patients with multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as HER2-positive.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Baseline LVEF >= 55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
- Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
- For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
Exclusion Criteria:
- Prior history of invasive breast cancer
- Stage IV (metastatic) breast cancer
- Patients with synchronous bilateral invasive breast cancer
- Prior systemic therapy for treatment of breast cancer
- Previous therapy with anthracyclines or taxanes for any malignancy
- Ulcerating or inflammatory breast cancer
- Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
- Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy
- History of other malignancy within 5 years prior to screening, with the exception of those patients who have a negligible risk of metastasis or death
- Cardiopulmonary dysfunction
- Dyspnea at rest
- Active or history of autoimmune disease or immune deficiency
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab/placebo, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or trastuzumab emtansine whichever occurs last
Exclusion Criteria Related to Trastuzumab Emtansine in the Adjuvant Setting:
- Patients who achieved pCR
- Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery
- Unable to complete surgery with curative intent after conclusion of neoadjuvant systemic therapy
- Patient discontinued treatment with trastuzumab because of toxicity during the neoadjuvant phase of the study
- Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, or sclerosis cholangitis
- Patients with Grade >=2 peripheral neuropathy
- Prior treatment with trastuzumab emtansine
Sites / Locations
- HCA Midwest Division
- New York University Medical Center PRIME; NYU Langone Medical Center
- Tennessee Oncology
- Hospital Sao Rafael - HSR
- Hospital Araujo Jorge; Departamento de Ginecologia E Mama
- Hospital Sao Lucas - PUCRS
- Hospital Nossa Senhora da Conceicao
- Hospital Perola Byington
- Tom Baker Cancer Centre-Calgary
- BCCA-Vancouver Cancer Centre
- Jewish General Hospital
- Hopital du Saint Sacrement
- Masarykuv onkologicky ustav
- Fakultni nemocnice Olomouc; Onkologicka klinika
- Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
- Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
- Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
- Sankt Elisabeth Krankenhaus; Gynaekology
- Rotkreuzklinikum München; Frauenklinik
- Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe
- St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik
- Universitätsfrauenklinik Ulm; Abteilung Gynäkologie
- Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
- Università degli Studi Federico II; Clinica di Oncologia Medica
- Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
- Policlinico Universitario Agostino Gemelli
- ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica
- ASST DI MONZA; Oncologia Medica
- Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
- Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
- IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
- National Hospital Organization Shikoku Cancer Center
- Fukushima Medical University Hospital
- Hiroshima City Hiroshima Citizens Hospital
- Hiroshima University Hospital
- National Hospital Organization Hokkaido Cancer Center
- Hyogo Cancer Center
- Kanagawa Cancer Center
- Tokai University Hospital
- Kumamoto Shinto General Hospital
- Niigata Cancer Center Hospital
- Saitama Medical University International Medical Center
- Toranomon Hospital
- Showa University Hospital
- Gachon University Gil Medical Center
- Korea University Anam Hospital
- Seoul National University Hospital
- Samsung Medical Centre; Oncology
- Instytut "Centrum Zdrowia Matki Polki"; Klinika Onkologii
- Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; Centr.Diagn.i Lecz.Chor.Piersi
- Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Onkologii Klinicznej
- Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
- Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
- FSBI National Medical Research Radiological Center; A. TSYB MEDICAL RADIOLOGICAL RESEARCH CENTER
- City Clinical Oncology Hospital
- SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
- Blokhin Cancer Research Center; Combined Treatment
- Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
- Petrov Research Inst. of Oncology
- Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- Hospital Universitario Virgen de La Arrixaca; Servicio De Oncologia
- Clinica Universitaria de Navarra; Servicio de Oncologia
- Hospital Clínic i Provincial; Servicio de Hematología y Oncología
- Complejo Asistencial Universitario De Burgos; Servicio de Oncologia
- Hospital Clinico de Granada; Servicio de Oncologia
- Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
- Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
- Clinica Universidad de Navarra Madrid; Servicio de Oncología
- Centro Integral Oncologico Clara Campal; Servicio de Oncología
- Hospital Universitario Virgen Macarena; Servicio de Oncologia
- Hospital Universitario Virgen del Rocio; Servicio de Oncologia
- China Medical University Hospital; Surgery
- Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
- Mackay Memorial Hospital; Dept of Surgery
- Chang Gung Medical Foundation - Linkou; Dept of Surgery
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Atezolizumab +ddAC-PacHP
Placebo + ddAC-PacHP
Participants will receive atezolizumab (atezo) 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 & cyclophosphamide 600 mg/m2 IV), followed by atezo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8mg/kg IV loading dose) Q3W for 4 cycles, & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant and adjuvant setting: atezo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo must be discontinued.
Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 & cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W for 4 cycles & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant & adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo must be discontinued.