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)

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial 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

This study (also known as IMpassion050) will evaluate the efficacy and safety of atezolizumab compared with placebo when given in combination with neoadjuvant dose-dense anthracycline (doxorubicin) + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab (ddAC-PacHP) in patients with early HER2-positive breast cancer (T2-4, N1-3, M0).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Atezolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab Emtansine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 454
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • GO
    • Goiania, GO, Brazil, 74605-070
      • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora da Conceicao
  • SP
    • Sao Paulo, SP, Brazil, 01317-000
      • Hospital Perola Byington
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre-Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint Sacrement
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
• Germany
  • Essen, Germany, 45136
    • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
  • Freiburg, Germany, 79110
    • Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
  • Hamburg, Germany, 20357
    • Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
  • Leipzig, Germany, 04277
    • Sankt Elisabeth Krankenhaus; Gynaekology
  • Muenchen, Germany, 80637
    • Rotkreuzklinikum München; Frauenklinik
  • Münster, Germany, 48149
    • Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe
  • Paderborn, Germany, 33098
    • St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik
  • Ulm, Germany, 89075
    • Universitätsfrauenklinik Ulm; Abteilung Gynäkologie
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Università degli Studi Federico II; Clinica di Oncologia Medica
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
  • Friuli-Venezia Giulia
    • Aviano, Friuli-Venezia Giulia, Italy, 33081
      • Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica
    • Monza, Lombardia, Italy, 20900
      • ASST DI MONZA; Oncologia Medica
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
  • Piemonte
    • Candiolo, Piemonte, Italy, 10060
      • Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
• Japan
  • Ehime, Japan, 791-0280
    • National Hospital Organization Shikoku Cancer Center
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Hokkaido, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center
  • Hyogo, Japan, 673-0021
    • Hyogo Cancer Center
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Kanagawa, Japan, 259-1193
    • Tokai University Hospital
  • Kumamoto, Japan, 862-8655
    • Kumamoto Shinto General Hospital
  • Miyagi, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Saitama, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 142-8666
    • Showa University Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 135-170
    • Samsung Medical Centre; Oncology
• Poland
  • ?ód?, Poland, 93-338
    • Instytut "Centrum Zdrowia Matki Polki"; Klinika Onkologii
  • Gliwice, Poland, 44-101
    • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; Centr.Diagn.i Lecz.Chor.Piersi
  • Grudzi?dz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Onkologii Klinicznej
  • Kraków, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
  • Warszawa, Poland, 02-781
    • Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
• Russian Federation
  • Sankt Petersburg, Russian Federation, 197758
    • Petrov Research Inst. of Oncology
  • Kaluga
    • Obninsk, Kaluga, Russian Federation, 249036
      • FSBI National Medical Research Radiological Center; A. TSYB MEDICAL RADIOLOGICAL RESEARCH CENTER
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 143423
      • City Clinical Oncology Hospital
    • Moskva, Moskovskaja Oblast, Russian Federation, 111123
      • SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
    • Moskva, Moskovskaja Oblast, Russian Federation, 115478
      • Blokhin Cancer Research Center; Combined Treatment
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Burgos, Spain, 09006
    • Complejo Asistencial Universitario De Burgos; Servicio de Oncologia
  • Granada, Spain, 18016
    • Hospital Clinico de Granada; Servicio de Oncologia
  • Jaen, Spain, 23007
    • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
  • Lerida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra Madrid; Servicio de Oncología
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal; Servicio de Oncología
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
    • Sant Andreu de La Barca, Barcelona, Spain, 08740
      • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Universitario Virgen de La Arrixaca; Servicio De Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oncologia
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital; Surgery
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital; Dept of Surgery
  • Taipei City, Taiwan, 11259
    • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou; Dept of Surgery
• United States
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Division
  • New York
    • New York, New York, United States, 10016
      • New York University Medical Center PRIME; NYU Langone Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Nashville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab +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.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedule specified in the respective arm.; Other Names: Tecentriq; Drug: Doxorubicin; Doxorubicin will be administered as per the schedule specified in the respective arm.; Other Names: Adriamycin; Drug: Cyclophosphamide; Cyclophosphamide will be administered as per the schedule specified in the respective arm.; Other Names: Cytoxan; Neosar; Drug: Paclitaxel; Paclitaxel will be administered as per the schedule specified in the respective arm.; Other Names: Taxol; Drug: Trastuzumab; Trastuzumab will be administered as per the schedule specified in the respective arm.; Other Names: Herceptin; Drug: Pertuzumab; Pertuzumab will be administered as per the schedule specified in the respective arm.; Other Names: Perjeta; Drug: Trastuzumab Emtansine; Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.; Other Names: Kadcyla
Placebo Comparator: Placebo + ddAC-PacHP; 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.	Drug: Doxorubicin; Doxorubicin will be administered as per the schedule specified in the respective arm.; Other Names: Adriamycin; Drug: Cyclophosphamide; Cyclophosphamide will be administered as per the schedule specified in the respective arm.; Other Names: Cytoxan; Neosar; Drug: Paclitaxel; Paclitaxel will be administered as per the schedule specified in the respective arm.; Other Names: Taxol; Drug: Trastuzumab; Trastuzumab will be administered as per the schedule specified in the respective arm.; Other Names: Herceptin; Drug: Pertuzumab; Pertuzumab will be administered as per the schedule specified in the respective arm.; Other Names: Perjeta; Drug: Trastuzumab Emtansine; Participants without pCR have the option of receiving adjuvant atezolizumab/placebo combined with Trastuzumab Emtansine 3.6 mg/kg IV Q3W.; Other Names: Kadcyla; Drug: Placebo; Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pathological Complete Response (pCR) in the PD-L1-Positive Population (IC 1/2/3)	pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer [AJCC] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (estrogen receptor (ER) positive and/or progesterone receptor (PgR) positive vs. ER negative and PgR negative).	From randomization to approximately 6 months
pCR in the ITT Population	pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer [AJCC] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (ER positive and/or PgR positive vs. ER negative and PgR negative).	From randomization to approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With pCR Based on Hormone Receptor Status	pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor [ER]/progesterone receptor [PgR] positive or ER/PgR negative).	From randomization to approximately 24 months
Percentage of Participants With pCR in the PD-L1-Negative Population	pCR (ypT0/is ypN0) in the IC 0 Population	From randomization to approximately 24 months
Event-Free Survival (EFS)	EFS defined as the time from randomization to the first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause, whichever occurs first, in all patients and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3).	From randomization to first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause (up to approximately 54 months)
Mean Changes From Baseline in Function (Role, Physical)	EORTC QLQ-C30 is a self-reported questionnaire that included functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), global health scale/quality of life (GHS/QOL) and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Questions 1-28 on the QLQ-C30 were on a 4-point scale (1=Not at All to 4=Very Much). Questions 29-30 (GHS scale) were on a 7-point scale (1=Very Poor to 7=Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement).	Baseline; Day 1 of Cycle 1-9, on Day 1 of every other cycle thereafter until Cycle 22; at the treatment discontinuation or early termination visit and follow up visit. Cycle 1-4, each cycle is 14 days. Cycle 5-22, each cycle is 21 days.
Mean Changes From Baseline in Global Health Status	EORTC QLQ-C30 is a self-reported questionnaire that included functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), GHS/QOL and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Questions 1-28 on the QLQ-C30 were on a 4-point scale (1=Not at All to 4=Very Much). Questions 29-30 (GHS scale) were on a 7-point scale (1=Very Poor to 7=Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement).	Baseline; Day 1 of Cycle 1-9, on Day 1 of every other cycle thereafter until Cycle 22; at the treatment discontinuation or early termination visit and follow up visit. Cycle 1-4, each cycle is 14 days. Cycle 5-22, each cycle is 21 days.
Maximum Serum Concentration (Cmax) of Atezolizumab	Cmax is the maximum (or peak) concentration that a study drug achieves in the body.	30 minutes post infusion on Day 1 Cycle (C) 1.
Minimum Serum Concentration (Cmin) of Atezolizumab	Cmin is the minimum (or trough) concentration that a study drug achieves in the body.	Pre-dose on Day 1 Cycle (C) 2, 3, 4, 8, 12, 16, ATDV (an average of 1 year). C 2-4, each C is 14 days. C 8-16, each C is 21 days. With protocol version 5, collection is only required ATDV/completion (an average of 1 year).
Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum		Pre-dose on Day 1 Cycle (C) 8, 12, and at treatment discontinuation visit (ATDV) (an average of 1 year). C 1-4, each C is 14 days. C 8-12, each C is 21 days. With protocol version 5, collection is only required ATDV/completion (an average of 1 year).
Cmax of Trastuzumab Emtansine in Serum	Cmax is the maximum (or peak) concentration that a study drug achieves in the body.	Day 1 of Cycle 9 and Cycle 12, at treatment disontinuation visit (an average of 1 year). Cycle 9 and 12 are each 21 days. With protocol version 5, collection is only required at the time of treatment discontinuation/completion (an average of 1 year).
Cmin of Trastuzumab Emtansine in Serum	Cmin is the minimum (or trough) concentration that a study drug achieves in the body.	Day 1 of Cycle 9 and Cycle 12, at treatment disontinuation visit (an average of 1 year). Cycle 9 and 12 are each 21 days. With protocol version 5, collection is only required at the time of treatment discontinuation/completion (an average of 1 year).
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab	Participants were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be treatment-emergent ADA-negative if they were ADA-negative or were missing data at baseline and all post-baseline samples were negative, or if they were ADA-positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer units greater than the titer of the baseline sample (treatment unaffected).	Day 1 Cycle (C) 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit (ATDV) (an average of 1 year). C 1-4, each C is 14 days. C 8-16, each C is 21 days. With protocol version 5, collection is only required ATDV/completion (an average of 1 year).
Number of Participants With Treatment-Emergent ADAs to Trastuzumab	Participants were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be treatment-emergent ADA-negative if they were ADA-negative or were missing data at baseline and all post-baseline samples were negative, or if they were ADA-positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer units greater than the titer of the baseline sample (treatment unaffected).	Day 1 Cycle (C) 1, 8, 12 and at treatment discontinuation visit (ATDV) (an average of 1 year). C 1-4, each C is 14 days. C 8-12, each C is 21 days. With protocol version 5, collection is only required ATDV/completion (an average of 1 year).
Number of Participants With Treatment-Emergent ADAs to Pertuzumab	Participants were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be treatment-emergent ADA-negative if they were ADA-negative or were missing data at baseline and all post-baseline samples were negative, or if they were ADA-positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer units greater than the titer of the baseline sample (treatment unaffected).	Day 1 of Cycle (C) 1, 8, 12, and at treatment discontinuation visit (ATDV) (an average of 1 year). C 1-4, each C is 14 days. C 8-12, each C is 21 days. With protocol version 5, collection is only required ATDV/completion (an average of 1 year).
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine	Participants were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be treatment-emergent ADA-negative if they were ADA-negative or were missing data at baseline and all post-baseline samples were negative, or if they were ADA-positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer units greater than the titer of the baseline sample (treatment unaffected).	Day 1 of Cycle 9 and Cycle 12, at treatment disontinuation visit (an average of 1 year). Cycle 9 and 12 are each 21 days. With protocol version 5, collection is only required at the time of treatment discontinuation/completion (an average of 1 year).
Percentage of Participants With pCR Based on PIK3CA Mutation Status	pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer [AJCC] staging system, 8th edition).	From randomization to approximately 24 months
EFS Based on PIK3CA Mutation Status		From randomization to first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause (up to approximately 54 months)
DFS Based on PIK3CA Mutation Status		Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)
OS Based on PIK3CA Mutation Status		From randomization to date of death from any cause (up to approximately 54 months)
Disease-Free Survival (DFS)	DFS defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first, in all patients who undergo surgery and based upon PD-L1 status (IC 0; IC 1/2/3).	Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)
Overall Survival (OS)	OS defined as the time from randomization to death from any cause in all participants and based upon PD-L1 status (IC 0; IC 1/2/3).	From randomization to date of death from any cause (up to approximately 54 months)
Percentage of Participants With Adverse Events		From randomization up end of study (approximately 4 years and 7 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Huober J, Barrios CH, Niikura N, Jarzab M, Chang YC, Huggins-Puhalla SL, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E, Zhang H; IMpassion050 Trial Investigators. Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022 Sep 1;40(25):2946-2956. doi: 10.1200/JCO.21.02772. Epub 2022 Jun 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2019
• Primary Completion (Actual): February 5, 2021
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: October 30, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): November 5, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Immunoconjugates; Immunotoxins; Trastuzumab; Atezolizumab; Ado-Trastuzumab Emtansine; Cyclophosphamide; Doxorubicin; Paclitaxel; Pertuzumab; Maytansine
• Other Study ID Numbers: BO40747

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No