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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)

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ClinicalTrials.gov Identifier: NCT03726879
Recruitment Status : Active, not recruiting
First Posted : November 1, 2018
Results First Posted : March 25, 2022
Last Update Posted : August 31, 2022
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 30, 2018
First Posted Date  ICMJE November 1, 2018
Results First Submitted Date  ICMJE January 21, 2022
Results First Posted Date  ICMJE March 25, 2022
Last Update Posted Date August 31, 2022
Actual Study Start Date  ICMJE January 11, 2019
Actual Primary Completion Date February 5, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2022)
  • Percentage of Participants With Pathological Complete Response (pCR) in the PD-L1-Positive Population (IC 1/2/3) [ Time Frame: From randomization to approximately 6 months ]
    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).
  • pCR in the ITT Population [ Time Frame: From randomization to approximately 6 months ]
    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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 30, 2018)
Percentage of Participants with Pathological Complete Response (pCR) [ Time Frame: From randomization to approximately 24 months ]
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) in the intent-to-treat (ITT) population.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2022)
  • Percentage of Participants With pCR Based on Hormone Receptor Status [ Time Frame: From randomization to approximately 24 months ]
    pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor [ER]/progesterone receptor [PgR] positive or ER/PgR negative).
  • Percentage of Participants With pCR in the PD-L1-Negative Population [ Time Frame: From randomization to approximately 24 months ]
    pCR (ypT0/is ypN0) in the IC 0 Population
  • Event-Free Survival (EFS) [ Time Frame: 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) ]
    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).
  • Disease-Free Survival (DFS) [ Time Frame: Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months) ]
    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 hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3).
  • Overall Survival (OS) [ Time Frame: From randomization to date of death from any cause (up to approximately 54 months) ]
    OS defined as the time from randomization to death from any cause 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).
  • Mean Changes From Baseline in Function (Role, Physical) [ Time Frame: 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. ]
    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).
  • Mean Changes From Baseline in Global Health Status [ Time Frame: 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. ]
    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).
  • Percentage of Participants With Adverse Events [ Time Frame: From randomization up until clinical cut-off date (approximately 24 months) ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: 30 minutes post infusion on Day 1 Cycle (C) 1. ]
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: 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). ]
    Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
  • Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum [ Time Frame: 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 [ Time Frame: 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). ]
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
  • Cmin of Trastuzumab Emtansine in Serum [ Time Frame: 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 is the minimum (or trough) concentration that a study drug achieves in the body.
  • Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: 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). ]
    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).
  • Number of Participants With Treatment-Emergent ADAs to Trastuzumab [ Time Frame: 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). ]
    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).
  • Number of Participants With Treatment-Emergent ADAs to Pertuzumab [ Time Frame: 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). ]
    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).
  • Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine [ Time Frame: 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). ]
    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).
  • Percentage of Participants With pCR Based on PIK3CA Mutation Status [ Time Frame: From randomization to approximately 24 months ]
    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).
  • EFS Based on PIK3CA Mutation Status [ Time Frame: 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 Frame: Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months) ]
  • OS Based on PIK3CA Mutation Status [ Time Frame: From randomization to date of death from any cause (up to approximately 54 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2018)
  • Percentage of Participants with pCR Based on Hormone Receptor Status [ Time Frame: From randomization to approximately 24 months ]
    pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor [ER]/progesterone receptor [PgR] positive or ER/PgR negative).
  • Percentage of Participants with pCR Based on PD-L1 Status [ Time Frame: From randomization to approximately 24 months ]
    pCR (ypT0/is ypN0) based upon PD-L1 status (IC 0; IC 1/2/3)
  • Event-Free Survival (EFS) [ Time Frame: From randomization to first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause (up to approximately 48 months) ]
    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.
  • Disease-Free Survival (DFS) [ Time Frame: From time from surgery to first documented disease recurrence or death from any cause (up to approximately 48 months) ]
    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.
  • Overall Survival (OS) [ Time Frame: From randomization to date of death from any cause (up to approximately 48 months) ]
    OS defined as the time from randomization to death from any cause in all patients.
  • Mean Changes From Baseline in Function (Role, Physical) [ Time Frame: 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 score in function (role, physical) will be assessed by the functional scales of EORTC QLQ-C30.
  • Mean Changes From Baseline in Global Health Status [ Time Frame: 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 will be assessed by the GHC/HRQoL scales of the EORTC QLQ-C30.
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline to end of study (approximately 48 months) ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]
    Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
  • Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]
  • Percentage of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]
  • Percentage of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) to Trastuzumab [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]
  • Percentage of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) to Pertuzumab [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
    Other Name: Tecentriq
  • Drug: Placebo
    Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Doxorubicin
    Doxorubicin will be administered as per the schedule specified in the respective arm.
    Other Name: 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 Name: Taxol
  • Drug: Trastuzumab
    Trastuzumab will be administered as per the schedule specified in the respective arm.
    Other Name: Herceptin
  • Drug: Pertuzumab
    Pertuzumab will be administered as per the schedule specified in the respective arm.
    Other Name: 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 Name: Kadcyla
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Drug: Paclitaxel
    • Drug: Trastuzumab
    • Drug: Pertuzumab
    • Drug: Trastuzumab Emtansine
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
    • Drug: Paclitaxel
    • Drug: Trastuzumab
    • Drug: Pertuzumab
    • Drug: Trastuzumab Emtansine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 11, 2021)
454
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2018)
224
Estimated Study Completion Date  ICMJE August 24, 2023
Actual Primary Completion Date February 5, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   Czechia,   Germany,   Italy,   Japan,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Taiwan,   United States
Removed Location Countries China
 
Administrative Information
NCT Number  ICMJE NCT03726879
Other Study ID Numbers  ICMJE BO40747
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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).
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Chugai Pharmaceutical
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP