Trial Outcomes & Findings for 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 (NCT NCT03726879)

Last Updated: 2024-11-05

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

454 participants

Primary outcome timeframe

From randomization to approximately 6 months

Results posted on

2024-11-05

Participant Flow

The study was conducted at 74 centers in 12 countries.

A total of 669 participants were screened, of which a total of 454 participants were enrolled.

Participant milestones

Participant milestones
Measure	Atezolizumab +ddAC-PacHP 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.	Placebo + ddAC-PacHP 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 Study STARTED	226	228
Overall Study COMPLETED	206	205
Overall Study NOT COMPLETED	20	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Atezolizumab +ddAC-PacHP 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.	Placebo + ddAC-PacHP 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 Study Death	11	13
Overall Study Physician Decision	0	2
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	5	6
Overall Study TSH result is unstable	0	1
Overall Study Disease relapse	1	0
Overall Study Lost to Follow-up	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atezolizumab +ddAC-PacHP n=226 Participants 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.	Placebo + ddAC-PacHP n=228 Participants 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 n=454 Participants Total of all reporting groups
Age, Continuous	50.3 Years STANDARD_DEVIATION 10.7 • n=5 Participants	50.8 Years STANDARD_DEVIATION 10.4 • n=7 Participants	50.6 Years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	225 Participants n=5 Participants	227 Participants n=7 Participants	452 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	26 Participants n=5 Participants	33 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	195 Participants n=5 Participants	191 Participants n=7 Participants	386 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	62 Participants n=5 Participants	66 Participants n=7 Participants	128 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized White	149 Participants n=5 Participants	142 Participants n=7 Participants	291 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to approximately 6 months

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=109 Participants 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.	Atezolizumab +ddAC-PacHP n=109 Participants 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.
Percentage of Participants With Pathological Complete Response (pCR) in the PD-L1-Positive Population (IC 1/2/3)	72.5 Percentage of Participants Interval 63.1 to 80.6	64.2 Percentage of Participants Interval 54.47 to 73.17

PRIMARY outcome

Timeframe: From randomization to approximately 6 months

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

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).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
pCR in the ITT Population	62.7 Percentage of Participants Interval 56.09 to 69.01	62.4 Percentage of Participants Interval 55.72 to 68.73

SECONDARY outcome

Timeframe: From randomization to approximately 24 months

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor \[ER\]/progesterone receptor \[PgR\] positive or ER/PgR negative).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Percentage of Participants With pCR Based on Hormone Receptor Status ER+ and/or PgR+	54.7 Percentage of Participants	50.9 Percentage of Participants
Percentage of Participants With pCR Based on Hormone Receptor Status ER- and/or PgR-	71.2 Percentage of Participants	74.5 Percentage of Participants

SECONDARY outcome

Timeframe: From randomization to approximately 24 months

Population: 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.

pCR (ypT0/is ypN0) in the IC 0 Population

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=119 Participants 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.	Atezolizumab +ddAC-PacHP n=117 Participants 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.
Percentage of Participants With pCR in the PD-L1-Negative Population	53.8 Percentage of Participants Interval 44.41 to 62.96	60.7 Percentage of Participants Interval 51.23 to 69.59

SECONDARY outcome

Timeframe: 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)

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

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).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Event-Free Survival (EFS) All Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Event-Free Survival (EFS) PD-L1 IC1/2/3 Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached.	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Event-Free Survival (EFS) PD-L1 IC0 Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Event-Free Survival (EFS) ER/PgR Negative Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Event-Free Survival (EFS) ER/PgR Positive Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached

SECONDARY outcome

Timeframe: Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)

Population: The DFS-evaluable population is defined as participants in the ITT population who undergo surgery.

DFS defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first, in all patients who undergo surgery and based upon PD-L1 status (IC 0; IC 1/2/3).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=217 Participants 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.	Atezolizumab +ddAC-PacHP n=217 Participants 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.
Disease-Free Survival (DFS) All Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Disease-Free Survival (DFS) PD-L1 IC1/2/3	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Disease-Free Survival (DFS) PD-L1 IC0	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached

SECONDARY outcome

Timeframe: From randomization to date of death from any cause (up to approximately 54 months)

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

OS defined as the time from randomization to death from any cause in all participants and based upon PD-L1 status (IC 0; IC 1/2/3).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Overall Survival (OS) All Participants	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Overall Survival (OS) PD-L1 IC1/2/3	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached
Overall Survival (OS) PD-L1 IC0	NA Months The median time to event based on Kaplan-Meier estimates was not reached	NA Months The median time to event based on Kaplan-Meier estimates was not reached

SECONDARY outcome

Timeframe: 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.

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=224 Participants 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.	Atezolizumab +ddAC-PacHP n=223 Participants 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.
Mean Changes From Baseline in Function (Role, Physical) Role: FU5D457	-33.33 Units on a scale Standard Deviation NA Standard deviation (SD) was non-estimable as only 1 participant was evaluated for this category.	—
Mean Changes From Baseline in Function (Role, Physical) Role: Baseline	90.85 Units on a scale Standard Deviation 20.26	91.70 Units on a scale Standard Deviation 16.28
Mean Changes From Baseline in Function (Role, Physical) Role: Cycle (C) 2 Day (D) 1	-9.83 Units on a scale Standard Deviation 23.08	-13.06 Units on a scale Standard Deviation 23.02
Mean Changes From Baseline in Function (Role, Physical) Role: C3D1	-15.15 Units on a scale Standard Deviation 22.64	-17.88 Units on a scale Standard Deviation 26.20
Mean Changes From Baseline in Function (Role, Physical) Role: C4D1	-17.98 Units on a scale Standard Deviation 25.10	-22.27 Units on a scale Standard Deviation 27.04
Mean Changes From Baseline in Function (Role, Physical) Role: C5D1	-19.79 Units on a scale Standard Deviation 26.36	-24.08 Units on a scale Standard Deviation 28.21
Mean Changes From Baseline in Function (Role, Physical) Role: C6D1	-18.60 Units on a scale Standard Deviation 25.01	-20.70 Units on a scale Standard Deviation 25.46
Mean Changes From Baseline in Function (Role, Physical) Role: C7D1	-16.67 Units on a scale Standard Deviation 26.34	-19.21 Units on a scale Standard Deviation 25.50
Mean Changes From Baseline in Function (Role, Physical) Role: C8D1	-17.79 Units on a scale Standard Deviation 26.39	-21.25 Units on a scale Standard Deviation 26.48
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 1 D1	-26.24 Units on a scale Standard Deviation 31.27	-22.82 Units on a scale Standard Deviation 26.70
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 7 D43	-15.15 Units on a scale Standard Deviation 26.50	-15.48 Units on a scale Standard Deviation 22.31
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 13 D85	-15.24 Units on a scale Standard Deviation 26.99	-14.42 Units on a scale Standard Deviation 23.77
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 19 D127	-15.42 Units on a scale Standard Deviation 25.74	-14.30 Units on a scale Standard Deviation 24.26
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 25 D169	-15.88 Units on a scale Standard Deviation 22.99	-13.68 Units on a scale Standard Deviation 24.00
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 31 D211	-14.55 Units on a scale Standard Deviation 24.43	-13.24 Units on a scale Standard Deviation 23.69
Mean Changes From Baseline in Function (Role, Physical) Role: Adjuvant Week 37 D253	-15.43 Units on a scale Standard Deviation 27.35	-9.34 Units on a scale Standard Deviation 21.11
Mean Changes From Baseline in Function (Role, Physical) Role: End of Treatment (EOT)	-18.10 Units on a scale Standard Deviation 29.04	-14.04 Units on a scale Standard Deviation 25.18
Mean Changes From Baseline in Function (Role, Physical) Role: Follow-Up (FU) 1 D1	-17.16 Units on a scale Standard Deviation 23.21	-11.02 Units on a scale Standard Deviation 25.06
Mean Changes From Baseline in Function (Role, Physical) Role: FU2D92	-14.65 Units on a scale Standard Deviation 25.94	-9.17 Units on a scale Standard Deviation 23.24
Mean Changes From Baseline in Function (Role, Physical) Role: FU3D183	-10.42 Units on a scale Standard Deviation 21.71	-16.67 Units on a scale Standard Deviation 16.67
Mean Changes From Baseline in Function (Role, Physical) Role: FU4D274	-25.00 Units on a scale Standard Deviation 9.13	-27.78 Units on a scale Standard Deviation 25.46
Mean Changes From Baseline in Function (Role, Physical) Physical: Baseline	92.20 Units on a scale Standard Deviation 12.92	92.74 Units on a scale Standard Deviation 11.60
Mean Changes From Baseline in Function (Role, Physical) Physical: C2D1	-3.88 Units on a scale Standard Deviation 13.44	-4.32 Units on a scale Standard Deviation 9.75
Mean Changes From Baseline in Function (Role, Physical) Physical: C3D1	-7.18 Units on a scale Standard Deviation 12.91	-6.82 Units on a scale Standard Deviation 13.39
Mean Changes From Baseline in Function (Role, Physical) Physical: C4D1	-9.48 Units on a scale Standard Deviation 14.65	-11.98 Units on a scale Standard Deviation 17.67
Mean Changes From Baseline in Function (Role, Physical) Physical: C5D1	-10.67 Units on a scale Standard Deviation 15.91	-12.84 Units on a scale Standard Deviation 16.76
Mean Changes From Baseline in Function (Role, Physical) Physical: C6D1	-11.40 Units on a scale Standard Deviation 17.05	-12.25 Units on a scale Standard Deviation 15.97
Mean Changes From Baseline in Function (Role, Physical) Physical: C7D1	-11.45 Units on a scale Standard Deviation 17.43	-11.33 Units on a scale Standard Deviation 14.86
Mean Changes From Baseline in Function (Role, Physical) Physical: C8D1	-11.56 Units on a scale Standard Deviation 17.54	-13.30 Units on a scale Standard Deviation 17.11
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 1 D1	-12.19 Units on a scale Standard Deviation 19.27	-12.27 Units on a scale Standard Deviation 18.26
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 7 D43	-8.60 Units on a scale Standard Deviation 16.33	-8.96 Units on a scale Standard Deviation 14.74
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 13 D85	-8.88 Units on a scale Standard Deviation 15.04	-8.38 Units on a scale Standard Deviation 14.97
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 19 D127	-10.03 Units on a scale Standard Deviation 15.52	-9.22 Units on a scale Standard Deviation 15.17
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 25 D169	-8.45 Units on a scale Standard Deviation 14.34	-9.35 Units on a scale Standard Deviation 16.19
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 31 D211	-9.88 Units on a scale Standard Deviation 15.84	-7.80 Units on a scale Standard Deviation 13.69
Mean Changes From Baseline in Function (Role, Physical) Physical: Adjuvant Week 37 D253	-10.78 Units on a scale Standard Deviation 16.82	-7.77 Units on a scale Standard Deviation 13.67
Mean Changes From Baseline in Function (Role, Physical) Physical: EOT	-13.05 Units on a scale Standard Deviation 19.17	-8.20 Units on a scale Standard Deviation 15.78
Mean Changes From Baseline in Function (Role, Physical) Physical: FU1D1	-11.57 Units on a scale Standard Deviation 19.29	-8.06 Units on a scale Standard Deviation 18.11
Mean Changes From Baseline in Function (Role, Physical) Physical: FU2D92	-9.90 Units on a scale Standard Deviation 15.73	-3.33 Units on a scale Standard Deviation 12.52
Mean Changes From Baseline in Function (Role, Physical) Physical: FU3D183	-14.17 Units on a scale Standard Deviation 7.51	2.22 Units on a scale Standard Deviation 16.78
Mean Changes From Baseline in Function (Role, Physical) Physical: FU4D274	-6.67 Units on a scale Standard Deviation 11.93	0.00 Units on a scale Standard Deviation 20.00
Mean Changes From Baseline in Function (Role, Physical) Physical: FU5D457	60.00 Units on a scale Standard Deviation NA SD was non-estimable as only 1 participant was evaluated for this category.	—

SECONDARY outcome

Population: The PRO-evaluable population is defined as participants in the ITT population with a baseline and at least 1 post-baseline PRO assessment.

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).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=224 Participants 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.	Atezolizumab +ddAC-PacHP n=223 Participants 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.
Mean Changes From Baseline in Global Health Status C3D1	-8.33 Units on a scale Standard Deviation 20.93	-10.96 Units on a scale Standard Deviation 22.16
Mean Changes From Baseline in Global Health Status Baseline	76.79 Units on a scale Standard Deviation 19.05	76.49 Units on a scale Standard Deviation 19.33
Mean Changes From Baseline in Global Health Status C2D1	-6.31 Units on a scale Standard Deviation 19.54	-7.28 Units on a scale Standard Deviation 19.70
Mean Changes From Baseline in Global Health Status C4D1	-10.88 Units on a scale Standard Deviation 21.51	-13.67 Units on a scale Standard Deviation 22.47
Mean Changes From Baseline in Global Health Status C5D1	-12.63 Units on a scale Standard Deviation 23.66	-14.14 Units on a scale Standard Deviation 23.76
Mean Changes From Baseline in Global Health Status C6D1	-9.99 Units on a scale Standard Deviation 20.96	-12.33 Units on a scale Standard Deviation 22.10
Mean Changes From Baseline in Global Health Status C7D1	-10.52 Units on a scale Standard Deviation 21.59	-11.47 Units on a scale Standard Deviation 19.81
Mean Changes From Baseline in Global Health Status C8D1	-10.86 Units on a scale Standard Deviation 22.66	-12.72 Units on a scale Standard Deviation 22.45
Mean Changes From Baseline in Global Health Status Adjuvant Week 1 D1	-7.14 Units on a scale Standard Deviation 23.68	-7.89 Units on a scale Standard Deviation 21.89
Mean Changes From Baseline in Global Health Status Adjuvant Week 7 D43	-5.21 Units on a scale Standard Deviation 21.96	-7.51 Units on a scale Standard Deviation 22.97
Mean Changes From Baseline in Global Health Status Adjuvant Week 13 D85	-6.75 Units on a scale Standard Deviation 21.13	-7.07 Units on a scale Standard Deviation 22.31
Mean Changes From Baseline in Global Health Status Adjuvant Week 19 D127	-6.01 Units on a scale Standard Deviation 20.52	-7.20 Units on a scale Standard Deviation 21.47
Mean Changes From Baseline in Global Health Status Adjuvant Week 25 D169	-5.05 Units on a scale Standard Deviation 20.39	-8.02 Units on a scale Standard Deviation 21.10
Mean Changes From Baseline in Global Health Status Adjuvant Week 31 D211	-7.80 Units on a scale Standard Deviation 22.56	-7.29 Units on a scale Standard Deviation 21.75
Mean Changes From Baseline in Global Health Status Adjuvant Week 37 D253	-6.03 Units on a scale Standard Deviation 20.72	-5.95 Units on a scale Standard Deviation 21.71
Mean Changes From Baseline in Global Health Status EOT	-9.41 Units on a scale Standard Deviation 24.29	-5.96 Units on a scale Standard Deviation 22.08
Mean Changes From Baseline in Global Health Status FU1D1	-5.15 Units on a scale Standard Deviation 21.01	-3.90 Units on a scale Standard Deviation 21.64
Mean Changes From Baseline in Global Health Status FU2D92	-3.03 Units on a scale Standard Deviation 16.11	-1.25 Units on a scale Standard Deviation 19.55
Mean Changes From Baseline in Global Health Status FU3D183	-7.29 Units on a scale Standard Deviation 15.06	-8.33 Units on a scale Standard Deviation 8.33
Mean Changes From Baseline in Global Health Status FU4D274	-31.94 Units on a scale Standard Deviation 37.42	-13.89 Units on a scale Standard Deviation 12.73
Mean Changes From Baseline in Global Health Status FU5D457	-16.67 Units on a scale Standard Deviation NA SD was non-estimable as only 1 participant was evaluated for this category.	—

SECONDARY outcome

Timeframe: From randomization up end of study (approximately 4 years and 7 months)

Population: The safety-evaluable population is defined as participants who received at least one dose of any study drug.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=225 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Percentage of Participants With Adverse Events	100 Percentage of Participants	100 Percentage of Participants

SECONDARY outcome

Timeframe: 30 minutes post infusion on Day 1 Cycle (C) 1.

Population: 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.

Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP 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.	Atezolizumab +ddAC-PacHP n=219 Participants 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.
Maximum Serum Concentration (Cmax) of Atezolizumab	—	348 micrograms/milliliters (ug/mL) Standard Deviation 122

SECONDARY outcome

Timeframe: 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).

Population: 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.

Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Minimum Serum Concentration (Cmin) of Atezolizumab C2D1/predose	—	103 ug/mL Standard Deviation 40.3
Minimum Serum Concentration (Cmin) of Atezolizumab C3D1/predose	—	163 ug/mL Standard Deviation 44.4
Minimum Serum Concentration (Cmin) of Atezolizumab C4D1/predose	—	204 ug/mL Standard Deviation 51.9
Minimum Serum Concentration (Cmin) of Atezolizumab C8D1/predose	—	225 ug/mL Standard Deviation 97.1
Minimum Serum Concentration (Cmin) of Atezolizumab C12D1/predose	—	217 ug/mL Standard Deviation 101
Minimum Serum Concentration (Cmin) of Atezolizumab C16D1/predose	—	226 ug/mL Standard Deviation 114

SECONDARY outcome

Timeframe: 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).

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=225 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum Pertuzumab: C8D1/predose	94.8 ug/mL Standard Deviation 39.8	93.2 ug/mL Standard Deviation 40.7
Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum Pertuzumab: C12D1/predose	91.6 ug/mL Standard Deviation 59.7	87.7 ug/mL Standard Deviation 58.4
Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum Trastuzumab: C8D1/predose	56.5 ug/mL Standard Deviation 23.9	58.5 ug/mL Standard Deviation 29.1
Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum Trastuzumab: C12D1/predose	60.4 ug/mL Standard Deviation 30.9	62.4 ug/mL Standard Deviation 32.7

SECONDARY outcome

Timeframe: 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).

Population: 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.

Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=49 Participants 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.	Atezolizumab +ddAC-PacHP n=53 Participants 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.
Cmax of Trastuzumab Emtansine in Serum C9D1	80.5 ug/mL Standard Deviation 26.8	84.3 ug/mL Standard Deviation 29.0
Cmax of Trastuzumab Emtansine in Serum C12D1	82.0 ug/mL Standard Deviation 37.2	82.0 ug/mL Standard Deviation 32.2

SECONDARY outcome

Population: 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.

Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=49 Participants 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.	Atezolizumab +ddAC-PacHP n=53 Participants 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.
Cmin of Trastuzumab Emtansine in Serum	1.22 ug/mL Standard Deviation 1.49	2.18 ug/mL Standard Deviation 5.09

SECONDARY outcome

Timeframe: 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).

Population: The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.

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).

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP 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.	Atezolizumab +ddAC-PacHP n=225 Participants 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.
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab Baseline (BL): ADA Positive	—	1 Participants
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab BL: ADA Negative	—	224 Participants
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab Post-BL: Treatment-Emergent ADA Positive	—	7 Participants
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab Post-BL: Treatment-Emergent ADA Negative	—	218 Participants

SECONDARY outcome

Timeframe: 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).

Population: The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=225 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Number of Participants With Treatment-Emergent ADAs to Trastuzumab BL: ADA Positive	1 Participants	2 Participants
Number of Participants With Treatment-Emergent ADAs to Trastuzumab BL: ADA Negative	206 Participants	214 Participants
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Post-BL: Treatment-Emergent ADA Positive	0 Participants	1 Participants
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Post-BL: Treatment-Emergent ADA Negative	216 Participants	212 Participants

SECONDARY outcome

Timeframe: 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).

Population: The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=225 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Number of Participants With Treatment-Emergent ADAs to Pertuzumab BL: ADA Positive	3 Participants	6 Participants
Number of Participants With Treatment-Emergent ADAs to Pertuzumab BL: ADA Negative	206 Participants	210 Participants
Number of Participants With Treatment-Emergent ADAs to Pertuzumab Post-BL: Treatment-Emergent ADA Positive	3 Participants	4 Participants
Number of Participants With Treatment-Emergent ADAs to Pertuzumab Post-BL: Treatment-Emergent ADA Negative	214 Participants	209 Participants

SECONDARY outcome

Population: The immunogenicity analysis included all safety evealuable participants who had at least one baseline or post-baseline ADA result from at least one sample.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=55 Participants 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.	Atezolizumab +ddAC-PacHP n=57 Participants 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.
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine BL: ADA Positive	2 Participants	3 Participants
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine BL: ADA Negative	48 Participants	49 Participants
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine Post-BL: Treatment-Emergent ADA Positive	1 Participants	1 Participants
Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine Post-BL: Treatment-Emergent ADA Negative	54 Participants	56 Participants

SECONDARY outcome

Timeframe: From randomization to approximately 24 months

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
Percentage of Participants With pCR Based on PIK3CA Mutation Status Mutated	34 Participants	40 Participants
Percentage of Participants With pCR Based on PIK3CA Mutation Status Wildtype	101 Participants	98 Participants
Percentage of Participants With pCR Based on PIK3CA Mutation Status Missing	8 Participants	3 Participants

SECONDARY outcome

Timeframe: 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)

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
EFS Based on PIK3CA Mutation Status Missing	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.
EFS Based on PIK3CA Mutation Status Mutated	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.
EFS Based on PIK3CA Mutation Status Wildtype	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.

SECONDARY outcome

Timeframe: Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)

Population: The DFS-evaluable population is defined as participants in the ITT population who undergo surgery.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=217 Participants 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.	Atezolizumab +ddAC-PacHP n=217 Participants 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.
DFS Based on PIK3CA Mutation Status Missing	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.
DFS Based on PIK3CA Mutation Status Mutated	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.
DFS Based on PIK3CA Mutation Status Wildtype	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.

SECONDARY outcome

Timeframe: From randomization to date of death from any cause (up to approximately 54 months)

Population: The ITT population is defined as all randomized participants, regardless of whether the assigned study treatment was received.

Outcome measures

Outcome measures
Measure	Placebo + ddAC-PacHP n=228 Participants 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.	Atezolizumab +ddAC-PacHP n=226 Participants 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.
OS Based on PIK3CA Mutation Status Mutated	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.
OS Based on PIK3CA Mutation Status Missing	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.
OS Based on PIK3CA Mutation Status Wildtype	NA Months Too few events to calculate the median and 95% confidence intervals.	NA Months Too few events to calculate the median and 95% confidence intervals.

Adverse Events

Atezolizumab +ddAC-PacHP

Serious events: 65 serious events

Other events: 226 other events

Deaths: 11 deaths

Placebo + ddAC-PacHP

Serious events: 47 serious events

Other events: 225 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER