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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03726879
Recruitment Status : Active, not recruiting
First Posted : November 1, 2018
Results First Posted : March 25, 2022
Last Update Posted : November 22, 2022
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Atezolizumab
Drug: Placebo
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Paclitaxel
Drug: Trastuzumab
Drug: Pertuzumab
Drug: Trastuzumab Emtansine
Enrollment 454
Recruitment Details The study was conducted at 74 centers in 12 countries.
Pre-assignment Details A total of 669 participants were screened, of which a total of 454 participants were enrolled.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued. Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Period Title: Overall Study
Started 226 228
Completed 0 0
Not Completed 226 228
Reason Not Completed
Death             6             4
Physician Decision             0             2
Protocol Violation             0             1
Withdrawal by Subject             5             5
TSH result is unstable             0             1
Continuing on Study             215             215
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP Total
Hide Arm/Group Description Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued. Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued. Total of all reporting groups
Overall Number of Baseline Participants 226 228 454
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 226 participants 228 participants 454 participants
50.3  (10.7) 50.8  (10.4) 50.6  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 226 participants 228 participants 454 participants
Female
225
  99.6%
227
  99.6%
452
  99.6%
Male
1
   0.4%
1
   0.4%
2
   0.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 226 participants 228 participants 454 participants
Hispanic or Latino 26 33 59
Not Hispanic or Latino 195 191 386
Not Reported 5 4 9
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 226 participants 228 participants 454 participants
American Indian or Alaska Native 1 1 2
Asian 62 66 128
Black or African American 8 13 21
White 149 142 291
Multiple 2 3 5
Unknown 4 3 7
1.Primary Outcome
Title Percentage of Participants With Pathological Complete Response (pCR) in the PD-L1-Positive Population (IC 1/2/3)
Hide Description 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).
Time Frame From randomization to approximately 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The PD-L1-positive population is defined as participants in the Intent-to-Treat (ITT) population whose PD-L1 status is IC1/2/3 at the time of randomization.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 109 109
Measure Type: Number
Unit of Measure: Percentage of Participants
64.2 72.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atezolizumab +ddAC-PacHP, Placebo + ddAC-PacHP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1846
Comments The threshold for statistical significance was a p-value =0.048
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.37 to 1.21
Estimation Comments [Not Specified]
2.Primary Outcome
Title pCR in the ITT Population
Hide Description 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).
Time Frame From randomization to approximately 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 226 228
Measure Type: Number
Unit of Measure: Percentage of Participants
62.4 62.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atezolizumab +ddAC-PacHP, Placebo + ddAC-PacHP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9551
Comments The threshold for statistical significance was a p-value =0.002
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.67 to 1.46
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With pCR Based on Hormone Receptor Status
Hide Description pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor [ER]/progesterone receptor [PgR] positive or ER/PgR negative).
Time Frame From randomization to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 226 228
Measure Type: Number
Unit of Measure: Percentage of Participants
ER+ and/or PgR+ Number Analyzed 116 participants 117 participants
50.9 54.7
ER- and/or PgR- Number Analyzed 110 participants 111 participants
74.5 71.2
4.Secondary Outcome
Title Percentage of Participants With pCR in the PD-L1-Negative Population
Hide Description pCR (ypT0/is ypN0) in the IC 0 Population
Time Frame From randomization to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The PD-L1-negative population is defined as participants in the ITT population whose PD-L1 status is IC 0 at the time of randomization.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 117 119
Measure Type: Number
Unit of Measure: Percentage of Participants
60.7 53.8
5.Secondary Outcome
Title Event-Free Survival (EFS)
Hide Description 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).
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)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Disease-Free Survival (DFS)
Hide Description 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).
Time Frame Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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).
Time Frame From randomization to date of death from any cause (up to approximately 54 months)
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Mean Changes From Baseline in Function (Role, Physical)
Hide Description 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).
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The patient-reported outcomes (PRO)-evaluable population is defined as participants in the ITT population with a baseline and at least 1 post-baseline PRO assessment.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 223 224
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Role: Baseline Number Analyzed 223 participants 224 participants
91.70  (16.28) 90.85  (20.26)
Role: Cycle (C) 2 Day (D) 1 Number Analyzed 222 participants 222 participants
-13.06  (23.02) -9.83  (23.08)
Role: C3D1 Number Analyzed 219 participants 220 participants
-17.88  (26.20) -15.15  (22.64)
Role: C4D1 Number Analyzed 217 participants 216 participants
-22.27  (27.04) -17.98  (25.10)
Role: C5D1 Number Analyzed 218 participants 219 participants
-24.08  (28.21) -19.79  (26.36)
Role: C6D1 Number Analyzed 215 participants 216 participants
-20.70  (25.46) -18.60  (25.01)
Role: C7D1 Number Analyzed 210 participants 210 participants
-19.21  (25.50) -16.67  (26.34)
Role: C8D1 Number Analyzed 211 participants 208 participants
-21.25  (26.48) -17.79  (26.39)
Role: Adjuvant Week 1 D1 Number Analyzed 206 participants 202 participants
-22.82  (26.70) -26.24  (31.27)
Role: Adjuvant Week 7 D43 Number Analyzed 183 participants 176 participants
-15.48  (22.31) -15.15  (26.50)
Role: Adjuvant Week 13 D85 Number Analyzed 171 participants 163 participants
-14.42  (23.77) -15.24  (26.99)
Role: Adjuvant Week 19 D127 Number Analyzed 155 participants 147 participants
-14.30  (24.26) -15.42  (25.74)
Role: Adjuvant Week 25 D169 Number Analyzed 134 participants 127 participants
-13.68  (24.00) -15.88  (22.99)
Role: Adjuvant Week 31 D211 Number Analyzed 112 participants 110 participants
-13.24  (23.69) -14.55  (24.43)
Role: Adjuvant Week 37 D253 Number Analyzed 91 participants 94 participants
-9.34  (21.11) -15.43  (27.35)
Role: End of Treatment (EOT) Number Analyzed 108 participants 116 participants
-14.04  (25.18) -18.10  (29.04)
Role: Follow-Up (FU) 1 D1 Number Analyzed 62 participants 68 participants
-11.02  (25.06) -17.16  (23.21)
Role: FU2D92 Number Analyzed 20 participants 33 participants
-9.17  (23.24) -14.65  (25.94)
Role: FU3D183 Number Analyzed 3 participants 8 participants
-16.67  (16.67) -10.42  (21.71)
Role: FU4D274 Number Analyzed 3 participants 6 participants
-27.78  (25.46) -25.00  (9.13)
Role: FU5D457 Number Analyzed 0 participants 1 participants
-33.33 [1]   (NA)
Physical: Baseline Number Analyzed 223 participants 224 participants
92.74  (11.60) 92.20  (12.92)
Physical: C2D1 Number Analyzed 222 participants 221 participants
-4.32  (9.75) -3.88  (13.44)
Physical: C3D1 Number Analyzed 219 participants 220 participants
-6.82  (13.39) -7.18  (12.91)
Physical: C4D1 Number Analyzed 217 participants 216 participants
-11.98  (17.67) -9.48  (14.65)
Physical: C5D1 Number Analyzed 218 participants 219 participants
-12.84  (16.76) -10.67  (15.91)
Physical: C6D1 Number Analyzed 215 participants 216 participants
-12.25  (15.97) -11.40  (17.05)
Physical: C7D1 Number Analyzed 210 participants 210 participants
-11.33  (14.86) -11.45  (17.43)
Physical: C8D1 Number Analyzed 211 participants 208 participants
-13.30  (17.11) -11.56  (17.54)
Physical: Adjuvant Week 1 D1 Number Analyzed 206 participants 202 participants
-12.27  (18.26) -12.19  (19.27)
Physical: Adjuvant Week 7 D43 Number Analyzed 183 participants 176 participants
-8.96  (14.74) -8.60  (16.33)
Physical: Adjuvant Week 13 D85 Number Analyzed 171 participants 163 participants
-8.38  (14.97) -8.88  (15.04)
Physical: Adjuvant Week 19 D127 Number Analyzed 154 participants 147 participants
-9.22  (15.17) -10.03  (15.52)
Physical: Adjuvant Week 25 D169 Number Analyzed 134 participants 127 participants
-9.35  (16.19) -8.45  (14.34)
Physical: Adjuvant Week 31 D211 Number Analyzed 112 participants 110 participants
-7.80  (13.69) -9.88  (15.84)
Physical: Adjuvant Week 37 D253 Number Analyzed 91 participants 94 participants
-7.77  (13.67) -10.78  (16.82)
Physical: EOT Number Analyzed 109 participants 116 participants
-8.20  (15.78) -13.05  (19.17)
Physical: FU1D1 Number Analyzed 62 participants 68 participants
-8.06  (18.11) -11.57  (19.29)
Physical: FU2D92 Number Analyzed 20 participants 33 participants
-3.33  (12.52) -9.90  (15.73)
Physical: FU3D183 Number Analyzed 3 participants 8 participants
2.22  (16.78) -14.17  (7.51)
Physical: FU4D274 Number Analyzed 3 participants 6 participants
0.00  (20.00) -6.67  (11.93)
Physical: FU5D457 Number Analyzed 0 participants 1 participants
60.00 [2]   (NA)
[1]
Standard deviation (SD) was non-estimable as only 1 participant was evaluated for this category.
[2]
SD was non-estimable as only 1 participant was evaluated for this category.
9.Secondary Outcome
Title Mean Changes From Baseline in Global Health Status
Hide Description 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).
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO-evaluable population is defined as participants in the ITT population with a baseline and at least 1 post-baseline PRO assessment.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 223 224
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline Number Analyzed 223 participants 224 participants
76.49  (19.33) 76.79  (19.05)
C2D1 Number Analyzed 222 participants 222 participants
-7.28  (19.70) -6.31  (19.54)
C3D1 Number Analyzed 219 participants 220 participants
-10.96  (22.16) -8.33  (20.93)
C4D1 Number Analyzed 217 participants 216 participants
-13.67  (22.47) -10.88  (21.51)
C5D1 Number Analyzed 218 participants 219 participants
-14.14  (23.76) -12.63  (23.66)
C6D1 Number Analyzed 215 participants 216 participants
-12.33  (22.10) -9.99  (20.96)
C7D1 Number Analyzed 210 participants 210 participants
-11.47  (19.81) -10.52  (21.59)
C8D1 Number Analyzed 211 participants 208 participants
-12.72  (22.45) -10.86  (22.66)
Adjuvant Week 1 D1 Number Analyzed 206 participants 202 participants
-7.89  (21.89) -7.14  (23.68)
Adjuvant Week 7 D43 Number Analyzed 183 participants 176 participants
-7.51  (22.97) -5.21  (21.96)
Adjuvant Week 13 D85 Number Analyzed 171 participants 163 participants
-7.07  (22.31) -6.75  (21.13)
Adjuvant Week 19 D127 Number Analyzed 155 participants 147 participants
-7.20  (21.47) -6.01  (20.52)
Adjuvant Week 25 D169 Number Analyzed 134 participants 127 participants
-8.02  (21.10) -5.05  (20.39)
Adjuvant Week 31 D211 Number Analyzed 112 participants 110 participants
-7.29  (21.75) -7.80  (22.56)
Adjuvant Week 37 D253 Number Analyzed 91 participants 94 participants
-5.95  (21.71) -6.03  (20.72)
EOT Number Analyzed 109 participants 116 participants
-5.96  (22.08) -9.41  (24.29)
FU1D1 Number Analyzed 62 participants 68 participants
-3.90  (21.64) -5.15  (21.01)
FU2D92 Number Analyzed 20 participants 33 participants
-1.25  (19.55) -3.03  (16.11)
FU3D183 Number Analyzed 3 participants 8 participants
-8.33  (8.33) -7.29  (15.06)
FU4D274 Number Analyzed 3 participants 6 participants
-13.89  (12.73) -31.94  (37.42)
FU5D457 Number Analyzed 0 participants 1 participants
-16.67 [1]   (NA)
[1]
SD was non-estimable as only 1 participant was evaluated for this category.
10.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame From randomization up until clinical cut-off date (approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety-evaluable population is defined as participants who received at least one dose of any study drug.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 226 225
Measure Type: Number
Unit of Measure: Percentage of Participants
100 100
11.Secondary Outcome
Title Maximum Serum Concentration (Cmax) of Atezolizumab
Hide Description Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
Time Frame 30 minutes post infusion on Day 1 Cycle (C) 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK)-evaluable population is defined as all participants who received any dose of study medication and who have at least one post-baseline PK sample available.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 219 0
Mean (Standard Deviation)
Unit of Measure: micrograms/milliliters (ug/mL)
348  (122)
12.Secondary Outcome
Title Minimum Serum Concentration (Cmin) of Atezolizumab
Hide Description Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
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).
Hide Outcome Measure Data
Hide Analysis Population Description
The PK-evaluable population is defined as all participants who received any dose of study medication and who have at least one post-baseline PK sample available.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 226 0
Mean (Standard Deviation)
Unit of Measure: ug/mL
C2D1/predose Number Analyzed 222 participants 0 participants
103  (40.3)
C3D1/predose Number Analyzed 214 participants 0 participants
163  (44.4)
C4D1/predose Number Analyzed 212 participants 0 participants
204  (51.9)
C8D1/predose Number Analyzed 203 participants 0 participants
225  (97.1)
C12D1/predose Number Analyzed 166 participants 0 participants
217  (101)
C16D1/predose Number Analyzed 133 participants 0 participants
226  (114)
13.Secondary Outcome
Title Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum
Hide Description [Not Specified]
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).
Hide Outcome Measure Data
Hide Analysis Population Description
The PK-evaluable population is defined as all participants who received any dose of study medication and who have at least one post-baseline PK sample available.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 226 225
Mean (Standard Deviation)
Unit of Measure: ug/mL
Pertuzumab: C8D1/predose Number Analyzed 205 participants 201 participants
93.2  (40.7) 94.8  (39.8)
Pertuzumab: C12D1/predose Number Analyzed 150 participants 147 participants
87.7  (58.4) 91.6  (59.7)
Trastuzumab: C8D1/predose Number Analyzed 205 participants 201 participants
58.5  (29.1) 56.5  (23.9)
Trastuzumab: C12D1/predose Number Analyzed 150 participants 147 participants
62.4  (32.7) 60.4  (30.9)
14.Secondary Outcome
Title Cmax of Trastuzumab Emtansine in Serum
Hide Description Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
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).
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Cmin of Trastuzumab Emtansine in Serum
Hide Description Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
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).
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab
Hide Description 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).
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).
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 225 0
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline (BL): ADA Positive
1
   0.4%
BL: ADA Negative
224
  99.6%
Post-BL: Treatment-Emergent ADA Positive
7
   3.1%
Post-BL: Treatment-Emergent ADA Negative
218
  96.9%
17.Secondary Outcome
Title Number of Participants With Treatment-Emergent ADAs to Trastuzumab
Hide Description 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).
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).
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 225 225
Measure Type: Count of Participants
Unit of Measure: Participants
BL: ADA Positive Number Analyzed 220 participants 211 participants
2
   0.9%
1
   0.5%
BL: ADA Negative Number Analyzed 220 participants 211 participants
218
  99.1%
210
  99.5%
Post-BL: Treatment-Emergent ADA Positive Number Analyzed 216 participants 214 participants
1
   0.5%
0
   0.0%
Post-BL: Treatment-Emergent ADA Negative Number Analyzed 216 participants 214 participants
215
  99.5%
214
 100.0%
18.Secondary Outcome
Title Number of Participants With Treatment-Emergent ADAs to Pertuzumab
Hide Description 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).
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).
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 225 225
Measure Type: Count of Participants
Unit of Measure: Participants
BL: ADA Positive Number Analyzed 221 participants 211 participants
6
   2.7%
3
   1.4%
BL: ADA Negative Number Analyzed 221 participants 211 participants
215
  97.3%
208
  98.6%
Post-BL: Treatment-Emergent ADA Positive Number Analyzed 216 participants 214 participants
13
   6.0%
12
   5.6%
Post-BL: Treatment-Emergent ADA Negative Number Analyzed 216 participants 214 participants
203
  94.0%
202
  94.4%
19.Secondary Outcome
Title Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine
Hide Description 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).
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).
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Percentage of Participants With pCR Based on PIK3CA Mutation Status
Hide Description 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).
Time Frame From randomization to approximately 24 months
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Hide Analysis Population Description
The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description:
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued.
Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
Overall Number of Participants Analyzed 226 228
Measure Type: Count of Participants
Unit of Measure: Participants
Mutated Number Analyzed 67 participants 61 participants
40
  59.7%
34
  55.7%
Wildtype Number Analyzed 150 participants 155 participants
98
  65.3%
101
  65.2%
Missing Number Analyzed 9 participants 12 participants
3
  33.3%
8
  66.7%
21.Secondary Outcome
Title EFS Based on PIK3CA Mutation Status
Hide Description [Not Specified]
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)
Outcome Measure Data Not Reported
22.Secondary Outcome
Title DFS Based on PIK3CA Mutation Status
Hide Description [Not Specified]
Time Frame Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)
Outcome Measure Data Not Reported
23.Secondary Outcome
Title OS Based on PIK3CA Mutation Status
Hide Description [Not Specified]
Time Frame From randomization to date of death from any cause (up to approximately 54 months)
Outcome Measure Data Not Reported
Time Frame From randomization up until clinical cut-off date (approximately 24 months)
Adverse Event Reporting Description AEs were recorded for the safety-evaluable population which included all randomized participants who received any dose of study drug.
 
Arm/Group Title Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Hide Arm/Group Description Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo was discontinued. Participants received 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 continued 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 did not achieve pCR had option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo was discontinued.
All-Cause Mortality
Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Affected / at Risk (%) Affected / at Risk (%)
Total   6/226 (2.65%)      4/225 (1.78%)    
Hide Serious Adverse Events
Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   62/226 (27.43%)      44/225 (19.56%)    
Blood and lymphatic system disorders     
ANAEMIA  1  1/226 (0.44%)  1 1/225 (0.44%)  1
APLASTIC ANAEMIA  1  0/226 (0.00%)  0 1/225 (0.44%)  1
FEBRILE NEUTROPENIA  1  10/226 (4.42%)  12 3/225 (1.33%)  3
LEUKOPENIA  1  0/226 (0.00%)  0 1/225 (0.44%)  1
NEUTROPENIA  1  1/226 (0.44%)  1 2/225 (0.89%)  3
Cardiac disorders     
ATRIAL FIBRILLATION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
ATRIAL TACHYCARDIA  1  0/226 (0.00%)  0 1/225 (0.44%)  1
CARDIAC FAILURE  1  3/226 (1.33%)  3 5/225 (2.22%)  6
CARDIAC FAILURE ACUTE  1  0/226 (0.00%)  0 1/225 (0.44%)  1
CARDIAC FAILURE CHRONIC  1  0/226 (0.00%)  0 1/225 (0.44%)  1
CARDIAC FAILURE CONGESTIVE  1  0/226 (0.00%)  0 1/225 (0.44%)  1
MITRAL VALVE INCOMPETENCE  1  0/226 (0.00%)  0 1/225 (0.44%)  1
SUPRAVENTRICULAR TACHYCARDIA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Endocrine disorders     
ADRENAL INSUFFICIENCY  1  4/226 (1.77%)  4 0/225 (0.00%)  0
HYPOPHYSITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
HYPOTHYROIDISM  1  1/226 (0.44%)  1 0/225 (0.00%)  0
SECONDARY ADRENOCORTICAL INSUFFICIENCY  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Eye disorders     
EYE DISCHARGE  1  0/226 (0.00%)  0 1/225 (0.44%)  1
MEIBOMIANITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Gastrointestinal disorders     
COLITIS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
DIARRHOEA  1  1/226 (0.44%)  1 1/225 (0.44%)  1
IMMUNE-MEDIATED PANCREATITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
NAUSEA  1  2/226 (0.88%)  2 1/225 (0.44%)  1
PANCREATITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
STOMATITIS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
General disorders     
ASTHENIA  1  0/226 (0.00%)  0 1/225 (0.44%)  1
CAPSULAR CONTRACTURE ASSOCIATED WITH BREAST IMPLANT  1  0/226 (0.00%)  0 1/225 (0.44%)  1
FATIGUE  1  1/226 (0.44%)  1 0/225 (0.00%)  0
PYREXIA  1  3/226 (1.33%)  3 3/225 (1.33%)  4
Hepatobiliary disorders     
BILIARY COLIC  1  0/226 (0.00%)  0 1/225 (0.44%)  1
HEPATIC HAEMORRHAGE  1  0/226 (0.00%)  0 1/225 (0.44%)  1
HYPERTRANSAMINASAEMIA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
STEATOHEPATITIS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
Infections and infestations     
ABSCESS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
ANAL ABSCESS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
APPENDICITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
BACTERAEMIA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
CELLULITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
COVID-19  1  2/226 (0.88%)  2 1/225 (0.44%)  1
CYSTITIS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
DEVICE RELATED INFECTION  1  2/226 (0.88%)  2 0/225 (0.00%)  0
FEBRILE INFECTION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
GASTRITIS BACTERIAL  1  0/226 (0.00%)  0 1/225 (0.44%)  1
HERPES ZOSTER  1  1/226 (0.44%)  1 0/225 (0.00%)  0
INFLUENZA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
MASTITIS  1  2/226 (0.88%)  3 0/225 (0.00%)  0
PNEUMOCYSTIS JIROVECII PNEUMONIA  1  0/226 (0.00%)  0 1/225 (0.44%)  1
PNEUMONIA  1  4/226 (1.77%)  4 2/225 (0.89%)  2
PNEUMONIA BACTERIAL  1  1/226 (0.44%)  1 0/225 (0.00%)  0
POST PROCEDURAL INFECTION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
POSTOPERATIVE WOUND INFECTION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
SEPSIS  1  2/226 (0.88%)  2 2/225 (0.89%)  2
SEPTIC SHOCK  1  1/226 (0.44%)  1 0/225 (0.00%)  0
STAPHYLOCOCCAL BACTERAEMIA  1  0/226 (0.00%)  0 1/225 (0.44%)  1
STAPHYLOCOCCAL INFECTION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
TOOTH ABSCESS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
UPPER RESPIRATORY TRACT INFECTION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
URINARY TRACT INFECTION  1  2/226 (0.88%)  2 0/225 (0.00%)  0
VASCULAR ACCESS SITE INFECTION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
VULVAL CELLULITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
WOUND INFECTION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Injury, poisoning and procedural complications     
IMPLANTATION COMPLICATION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
INFUSION RELATED REACTION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
LUMBAR VERTEBRAL FRACTURE  1  1/226 (0.44%)  1 0/225 (0.00%)  0
RADIATION PNEUMONITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
SEROMA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
WOUND COMPLICATION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Investigations     
EJECTION FRACTION DECREASED  1  0/226 (0.00%)  0 1/225 (0.44%)  1
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  1/226 (0.44%)  1 0/225 (0.00%)  0
GLYCOSYLATED HAEMOGLOBIN INCREASED  1  1/226 (0.44%)  1 0/225 (0.00%)  0
LIPASE INCREASED  1  1/226 (0.44%)  1 0/225 (0.00%)  0
OXYGEN SATURATION DECREASED  1  0/226 (0.00%)  0 1/225 (0.44%)  1
PLATELET COUNT DECREASED  1  1/226 (0.44%)  1 0/225 (0.00%)  0
TRANSAMINASES INCREASED  1  1/226 (0.44%)  1 0/225 (0.00%)  0
WHITE BLOOD CELL COUNT DECREASED  1  0/226 (0.00%)  0 1/225 (0.44%)  1
Metabolism and nutrition disorders     
DIABETES MELLITUS  1  1/226 (0.44%)  1 1/225 (0.44%)  1
HYPERGLYCAEMIA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
METABOLIC ACIDOSIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
MENINGIOMA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
NERVOUS SYSTEM NEOPLASM BENIGN  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Nervous system disorders     
MENINGITIS NONINFECTIVE  1  0/226 (0.00%)  0 1/225 (0.44%)  1
Product Issues     
DEVICE EXTRUSION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Psychiatric disorders     
DEPRESSION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  2/226 (0.88%)  2 1/225 (0.44%)  1
Reproductive system and breast disorders     
ADNEXAL TORSION  1  1/226 (0.44%)  1 0/225 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ACUTE RESPIRATORY DISTRESS SYNDROME  1  1/226 (0.44%)  1 0/225 (0.00%)  0
ALVEOLITIS  1  1/226 (0.44%)  1 1/225 (0.44%)  1
DYSPNOEA  1  1/226 (0.44%)  1 0/225 (0.00%)  0
DYSPNOEA EXERTIONAL  1  1/226 (0.44%)  1 0/225 (0.00%)  0
IMMUNE-MEDIATED PNEUMONITIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
INTERSTITIAL LUNG DISEASE  1  1/226 (0.44%)  1 0/225 (0.00%)  0
PLEURAL EFFUSION  1  0/226 (0.00%)  0 1/225 (0.44%)  1
PNEUMONITIS  1  9/226 (3.98%)  9 2/225 (0.89%)  2
PULMONARY EMBOLISM  1  1/226 (0.44%)  1 3/225 (1.33%)  3
Vascular disorders     
DEEP VEIN THROMBOSIS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
JUGULAR VEIN THROMBOSIS  1  1/226 (0.44%)  1 0/225 (0.00%)  0
SUBCLAVIAN VEIN THROMBOSIS  1  2/226 (0.88%)  2 0/225 (0.00%)  0
THROMBOSIS  1  0/226 (0.00%)  0 1/225 (0.44%)  1
VASCULAR PAIN  1  0/226 (0.00%)  0 1/225 (0.44%)  1
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atezolizumab +ddAC-PacHP Placebo + ddAC-PacHP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   226/226 (100.00%)      225/225 (100.00%)    
Blood and lymphatic system disorders     
ANAEMIA  1  114/226 (50.44%)  173 114/225 (50.67%)  217
LEUKOPENIA  1  37/226 (16.37%)  105 50/225 (22.22%)  122
LYMPHOPENIA  1  11/226 (4.87%)  21 13/225 (5.78%)  28
NEUTROPENIA  1  66/226 (29.20%)  168 76/225 (33.78%)  188
THROMBOCYTOPENIA  1  22/226 (9.73%)  31 20/225 (8.89%)  40
Endocrine disorders     
HYPERTHYROIDISM  1  22/226 (9.73%)  25 6/225 (2.67%)  7
HYPOTHYROIDISM  1  48/226 (21.24%)  59 21/225 (9.33%)  23
Eye disorders     
DRY EYE  1  15/226 (6.64%)  15 8/225 (3.56%)  8
Gastrointestinal disorders     
ABDOMINAL PAIN  1  15/226 (6.64%)  16 21/225 (9.33%)  23
ABDOMINAL PAIN UPPER  1  25/226 (11.06%)  29 29/225 (12.89%)  36
CONSTIPATION  1  67/226 (29.65%)  92 59/225 (26.22%)  78
DIARRHOEA  1  145/226 (64.16%)  333 137/225 (60.89%)  271
DRY MOUTH  1  13/226 (5.75%)  13 14/225 (6.22%)  15
DYSPEPSIA  1  25/226 (11.06%)  27 27/225 (12.00%)  41
GASTROOESOPHAGEAL REFLUX DISEASE  1  12/226 (5.31%)  19 14/225 (6.22%)  16
HAEMORRHOIDS  1  16/226 (7.08%)  16 14/225 (6.22%)  15
NAUSEA  1  145/226 (64.16%)  313 138/225 (61.33%)  281
STOMATITIS  1  49/226 (21.68%)  66 44/225 (19.56%)  54
VOMITING  1  77/226 (34.07%)  116 53/225 (23.56%)  86
General disorders     
ASTHENIA  1  96/226 (42.48%)  197 85/225 (37.78%)  189
CHILLS  1  8/226 (3.54%)  8 13/225 (5.78%)  14
FATIGUE  1  61/226 (26.99%)  104 38/225 (16.89%)  49
MALAISE  1  11/226 (4.87%)  20 16/225 (7.11%)  21
MUCOSAL INFLAMMATION  1  33/226 (14.60%)  41 29/225 (12.89%)  43
OEDEMA PERIPHERAL  1  14/226 (6.19%)  19 16/225 (7.11%)  17
PAIN  1  15/226 (6.64%)  20 15/225 (6.67%)  21
PYREXIA  1  44/226 (19.47%)  60 42/225 (18.67%)  66
Infections and infestations     
CONJUNCTIVITIS  1  14/226 (6.19%)  16 17/225 (7.56%)  17
NASOPHARYNGITIS  1  17/226 (7.52%)  20 15/225 (6.67%)  17
PARONYCHIA  1  13/226 (5.75%)  13 13/225 (5.78%)  16
UPPER RESPIRATORY TRACT INFECTION  1  19/226 (8.41%)  23 19/225 (8.44%)  20
URINARY TRACT INFECTION  1  23/226 (10.18%)  33 24/225 (10.67%)  29
Injury, poisoning and procedural complications     
INFUSION RELATED REACTION  1  39/226 (17.26%)  58 33/225 (14.67%)  41
PROCEDURAL PAIN  1  15/226 (6.64%)  15 18/225 (8.00%)  18
RADIATION SKIN INJURY  1  51/226 (22.57%)  53 40/225 (17.78%)  41
WOUND COMPLICATION  1  13/226 (5.75%)  14 16/225 (7.11%)  16
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  77/226 (34.07%)  126 63/225 (28.00%)  93
ASPARTATE AMINOTRANSFERASE INCREASED  1  65/226 (28.76%)  99 49/225 (21.78%)  77
BLOOD ALKALINE PHOSPHATASE INCREASED  1  10/226 (4.42%)  12 12/225 (5.33%)  12
BLOOD LACTATE DEHYDROGENASE INCREASED  1  12/226 (5.31%)  13 9/225 (4.00%)  9
EJECTION FRACTION DECREASED  1  14/226 (6.19%)  14 19/225 (8.44%)  25
LYMPHOCYTE COUNT DECREASED  1  13/226 (5.75%)  21 12/225 (5.33%)  19
NEUTROPHIL COUNT DECREASED  1  33/226 (14.60%)  69 29/225 (12.89%)  47
PLATELET COUNT DECREASED  1  15/226 (6.64%)  19 12/225 (5.33%)  16
WEIGHT DECREASED  1  24/226 (10.62%)  25 14/225 (6.22%)  14
WHITE BLOOD CELL COUNT DECREASED  1  13/226 (5.75%)  25 10/225 (4.44%)  16
Metabolism and nutrition disorders     
DECREASED APPETITE  1  45/226 (19.91%)  61 34/225 (15.11%)  43
HYPERGLYCAEMIA  1  13/226 (5.75%)  15 4/225 (1.78%)  5
HYPOKALAEMIA  1  12/226 (5.31%)  15 10/225 (4.44%)  12
HYPOMAGNESAEMIA  1  12/226 (5.31%)  20 14/225 (6.22%)  22
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  51/226 (22.57%)  75 51/225 (22.67%)  78
BACK PAIN  1  22/226 (9.73%)  27 18/225 (8.00%)  20
BONE PAIN  1  14/226 (6.19%)  15 16/225 (7.11%)  19
MYALGIA  1  45/226 (19.91%)  61 41/225 (18.22%)  65
PAIN IN EXTREMITY  1  25/226 (11.06%)  38 23/225 (10.22%)  31
Nervous system disorders     
DIZZINESS  1  23/226 (10.18%)  29 22/225 (9.78%)  29
DYSGEUSIA  1  32/226 (14.16%)  36 35/225 (15.56%)  40
HEADACHE  1  52/226 (23.01%)  81 48/225 (21.33%)  67
HYPOAESTHESIA  1  14/226 (6.19%)  15 9/225 (4.00%)  11
NEUROPATHY PERIPHERAL  1  43/226 (19.03%)  49 43/225 (19.11%)  58
PARAESTHESIA  1  15/226 (6.64%)  16 20/225 (8.89%)  24
PERIPHERAL SENSORY NEUROPATHY  1  46/226 (20.35%)  55 38/225 (16.89%)  43
POLYNEUROPATHY  1  13/226 (5.75%)  17 13/225 (5.78%)  15
Psychiatric disorders     
ANXIETY  1  8/226 (3.54%)  8 15/225 (6.67%)  17
INSOMNIA  1  38/226 (16.81%)  46 29/225 (12.89%)  34
Renal and urinary disorders     
DYSURIA  1  19/226 (8.41%)  23 16/225 (7.11%)  20
Reproductive system and breast disorders     
BREAST PAIN  1  8/226 (3.54%)  8 15/225 (6.67%)  16
Respiratory, thoracic and mediastinal disorders     
COUGH  1  37/226 (16.37%)  47 46/225 (20.44%)  62
DYSPNOEA  1  18/226 (7.96%)  21 22/225 (9.78%)  30
EPISTAXIS  1  28/226 (12.39%)  30 28/225 (12.44%)  37
OROPHARYNGEAL PAIN  1  12/226 (5.31%)  13 13/225 (5.78%)  14
RHINORRHOEA  1  24/226 (10.62%)  28 13/225 (5.78%)  17
Skin and subcutaneous tissue disorders     
ALOPECIA  1  145/226 (64.16%)  149 141/225 (62.67%)  150
DERMATITIS  1  20/226 (8.85%)  22 13/225 (5.78%)  14
DRY SKIN  1  21/226 (9.29%)  23 20/225 (8.89%)  21
ERYTHEMA  1  12/226 (5.31%)  19 17/225 (7.56%)  23
NAIL DISCOLOURATION  1  17/226 (7.52%)  17 24/225 (10.67%)  24
NAIL DISORDER  1  17/226 (7.52%)  19 21/225 (9.33%)  21
ONYCHOLYSIS  1  13/226 (5.75%)  15 6/225 (2.67%)  9
PRURITUS  1  33/226 (14.60%)  38 23/225 (10.22%)  33
RASH  1  65/226 (28.76%)  96 46/225 (20.44%)  58
Vascular disorders     
HOT FLUSH  1  23/226 (10.18%)  27 25/225 (11.11%)  28
HYPERTENSION  1  14/226 (6.19%)  23 13/225 (5.78%)  21
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
On February 5, 2021, the experimental treatment was discontinued and unblinded following the recommendation of the independent Data Monitoring Committee (iDMC) to stop treatment with atezolizumab/placebo.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03726879    
Other Study ID Numbers: BO40747
First Submitted: October 30, 2018
First Posted: November 1, 2018
Results First Submitted: January 21, 2022
Results First Posted: March 25, 2022
Last Update Posted: November 22, 2022