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

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

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 (estrogen receptor (ER) positive and/or progesterone receptor (PgR) positive vs. ER negative and PgR negative).

Time frame: 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.

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).

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.

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).

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.

Time frame: 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).

Time frame: 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.

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)

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).

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)

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

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.

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.

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.

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), 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.

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

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).

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.

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).

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).

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).

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).

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).

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).

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).

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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

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

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).

Time frame: 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) in the IC 0 Population

Time frame: 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.

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).

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.