A Study To Evaluate the Efficacy and Safety Of Atezolizum... | NCT03726879

NCT03726879

Status Module

Name	Class
Chugai Pharmaceutical	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Atezolizumab +ddAC-PacHP	Experimental	Participants will receive atezolizumab (atezo) 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 & cyclophosphamide 600 mg/m2 IV), followed by atezo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8mg/kg IV loading dose) Q3W for 4 cycles, & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant and adjuvant setting: atezo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo must be discontinued.	Drug: Atezolizumab Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel Drug: Trastuzumab Drug: Pertuzumab Drug: Trastuzumab Emtansine
Placebo + ddAC-PacHP	Placebo Comparator	Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 & cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W for 4 cycles & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant & adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, & pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo must be discontinued.

Name	Type	Description	Arm Group Labels	Other Names
Atezolizumab	Drug	Atezolizumab will be administered as per the schedule specified in the respective arm.	Atezolizumab +ddAC-PacHP

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With pCR Based on Hormone Receptor Status	pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor [ER]/progesterone receptor [PgR] positive or ER/PgR negative).	From randomization to approximately 24 months
Percentage of Participants With pCR in the PD-L1-Negative Population

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed diagnosis of HER2-positive breast cancer, and hormonal and PD-L1 status, as documented through central testing of a representative tumor tissue specimen
Primary breast tumor size of > 2 cm by any radiographic measurement
Stage at presentation: T2-T4, N1-N3, M0 as determined by AJCC staging system, 8th edition
Pathologic confirmation of nodal involvement with malignancy must be determined by fine needle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not permitted.
Patients with multifocal tumors are eligible provided at least one focus is sampled and centrally confirmed as HER2-positive.
Patients with multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as HER2-positive.
Eastern Cooperative Oncology Group Performance Status of 0 or 1
Baseline LVEF >= 55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment
For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

Prior history of invasive breast cancer
Stage IV (metastatic) breast cancer
Patients with synchronous bilateral invasive breast cancer
Prior systemic therapy for treatment of breast cancer
Previous therapy with anthracyclines or taxanes for any malignancy
Ulcerating or inflammatory breast cancer
Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy
History of other malignancy within 5 years prior to screening, with the exception of those patients who have a negligible risk of metastasis or death
Cardiopulmonary dysfunction
Dyspnea at rest
Active or history of autoimmune disease or immune deficiency
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab/placebo, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or trastuzumab emtansine whichever occurs last

Exclusion Criteria Related to Trastuzumab Emtansine in the Adjuvant Setting:

Patients who achieved pCR
Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery
Unable to complete surgery with curative intent after conclusion of neoadjuvant systemic therapy
Patient discontinued treatment with trastuzumab because of toxicity during the neoadjuvant phase of the study
Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, or sclerosis cholangitis
Patients with Grade >=2 peripheral neuropathy
Prior treatment with trastuzumab emtansine

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
HCA Midwest Division		Kansas City	Missouri	64132	United States
New York University Medical Center PRIME; NYU Langone Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35763704	Derived	Huober J, Barrios CH, Niikura N, Jarzab M, Chang YC, Huggins-Puhalla SL, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E, Zhang H; IMpassion050 Trial Investigators. Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022 Sep 1;40(25):2946-2956. doi: 10.1200/JCO.21.02772. Epub 2022 Jun 28.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 23, 2023	Aug 22, 2024

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Pathological Complete Response (pCR) in the PD-L1-Positive Population (IC 1/2/3)

pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer [AJCC] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (estrogen receptor (ER) positive and/or progesterone receptor (PgR) positive vs. ER negative and PgR negative).

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.

Posted

Number

Percentage of Participants

From randomization to approximately 6 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000109 OG001109

Title

Denominators

Categories

Title	Measurements
	OG00064.2(54.47 to 73.17) OG00172.5(63.10 to 80.60)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.1846	The threshold for statistical significance was a p-value =0.048	Odds Ratio (OR)	0.67			2-Sided	95	0.37	1.21					Superiority

Primary

pCR in the ITT Population

pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer [AJCC] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (ER positive and/or PgR positive vs. ER negative and PgR negative).

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

Posted

Number

Percentage of Participants

From randomization to approximately 6 months

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With pCR Based on Hormone Receptor Status

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

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

Posted

Number

Percentage of Participants

From randomization to approximately 24 months

ID	Title	Description
OG000	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.
OG001	Placebo + ddAC-PacHP

Secondary

Percentage of Participants With pCR in the PD-L1-Negative Population

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

Posted

Number

Percentage of Participants

From randomization to approximately 24 months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Event-Free Survival (EFS)

EFS defined as the time from randomization to the first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause, whichever occurs first, in all patients and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3).

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

Posted

Median

95% Confidence Interval

Months

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)

ID	Title	Description
OG000	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.

Secondary

Disease-Free Survival (DFS)

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

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

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	Placebo + ddAC-PacHP

Secondary

Overall Survival (OS)

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

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

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	Placebo + ddAC-PacHP

Secondary

Mean Changes From Baseline in Function (Role, Physical)

EORTC QLQ-C30 is a self-reported questionnaire that included functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), global health scale/quality of life (GHS/QOL) and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Questions 1-28 on the QLQ-C30 were on a 4-point scale (1=Not at All to 4=Very Much). Questions 29-30 (GHS scale) were on a 7-point scale (1=Very Poor to 7=Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement).

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.

Posted

Mean

Standard Deviation

Units on a scale

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.

ID	Title	Description
OG000	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.

Secondary

Mean Changes From Baseline in Global Health Status

EORTC QLQ-C30 is a self-reported questionnaire that included functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), GHS/QOL and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Questions 1-28 on the QLQ-C30 were on a 4-point scale (1=Not at All to 4=Very Much). Questions 29-30 (GHS scale) were on a 7-point scale (1=Very Poor to 7=Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement).

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

Posted

Mean

Standard Deviation

Units on a scale

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With Adverse Events

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

Posted

Number

Percentage of Participants

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Maximum Serum Concentration (Cmax) of Atezolizumab

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

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.

Posted

Mean

Standard Deviation

micrograms/milliliters (ug/mL)

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

ID	Title	Description
OG000	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.
OG001	Placebo + ddAC-PacHP

Secondary

Minimum Serum Concentration (Cmin) of Atezolizumab

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

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.

Posted

Mean

Standard Deviation

ug/mL

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).

ID	Title	Description
OG000	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.
OG001

Secondary

Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum

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.

Posted

Mean

Standard Deviation

ug/mL

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).

ID	Title	Description
OG000	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.
OG001	Placebo + ddAC-PacHP

Secondary

Cmax of Trastuzumab Emtansine in Serum

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

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.

Posted

Mean

Standard Deviation

ug/mL

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).

ID	Title	Description
OG000	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.

Secondary

Cmin of Trastuzumab Emtansine in Serum

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

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.

Posted

Mean

Standard Deviation

ug/mL

ID	Title	Description
OG000	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.

Secondary

Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab

Participants were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be treatment-emergent ADA-negative if they were ADA-negative or were missing data at baseline and all post-baseline samples were negative, or if they were ADA-positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer units greater than the titer of the baseline sample (treatment unaffected).

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

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	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.

Secondary

Number of Participants With Treatment-Emergent ADAs to Trastuzumab

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

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	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.

Secondary

Number of Participants With Treatment-Emergent ADAs to Pertuzumab

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

Posted

Count of Participants

Participants

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).

ID	Title	Description
OG000	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.

Secondary

Number of Participants With Treatment-Emergent ADAs to Trastuzumab Emtansine

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

Posted

Count of Participants

Participants

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With pCR Based on PIK3CA Mutation Status

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

Posted

Count of Participants

Participants

From randomization to approximately 24 months

ID	Title	Description
OG000	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.

Secondary

EFS Based on PIK3CA Mutation Status

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

Posted

Median

95% Confidence Interval

Months

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)

ID	Title	Description
OG000	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.
OG001	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.

Secondary

DFS Based on PIK3CA Mutation Status

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

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

OS Based on PIK3CA Mutation Status

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

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	11	226	65	226	226	226
EG001	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.	13	228	47	225	225	225

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Aplastic anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG00012 events10 affected226 at risk EG0013 events3 affected225 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0013 events2 affected225 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Atrial tachycardia	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Cardiac failure	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected226 at risk EG0016 events5 affected225 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Cardiomyopathy	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Restrictive cardiomyopathy	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected226 at risk EG0010 events0 affected225 at risk
Hypophysitis	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Hypothyroidism	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Secondary adrenocortical insufficiency	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Eye discharge	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Meibomianitis	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Colitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Immune-mediated pancreatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Asthenia	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Capsular contracture associated with breast implant	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected226 at risk EG0014 events3 affected225 at risk
Biliary colic	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Steatohepatitis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Sarcoidosis	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Abscess	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Anal abscess	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Appendicitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Bacteraemia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected226 at risk EG0011 events1 affected225 at risk
Cellulitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Cystitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Device related infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Febrile infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Gastritis bacterial	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Herpes zoster	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Mastitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 events3 affected226 at risk EG0010 events0 affected225 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected226 at risk EG0012 events2 affected225 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Post procedural infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Postoperative wound infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected226 at risk EG0012 events2 affected225 at risk
Septic shock	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Staphylococcal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Tooth abscess	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected226 at risk EG0010 events0 affected225 at risk
Vascular access site infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0012 events2 affected225 at risk
Vascular device infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Vulval cellulitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Wound infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Implantation complication	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Seroma	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Wound complication	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Ejection fraction decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0012 events2 affected225 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Glycosylated haemoglobin increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Lipase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Oxygen saturation decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Platelet count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Transaminases increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
White blood cell count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected226 at risk EG0010 events0 affected225 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Nervous system neoplasm benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Meningitis noninfective	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Device extrusion	Product Issues	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Depression	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Mental status changes	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected226 at risk EG0011 events1 affected225 at risk
Adnexal torsion	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Alveolitis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected225 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00010 events10 affected226 at risk EG0012 events2 affected225 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0013 events3 affected225 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected225 at risk
Subclavian vein thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected225 at risk
Thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk
Vascular pain	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected225 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG000179 events116 affected226 at risk EG001235 events118 affected225 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG000104 events37 affected226 at risk EG001130 events50 affected225 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG00021 events11 affected226 at risk EG00128 events13 affected225 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG000173 events66 affected226 at risk EG001197 events76 affected225 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG00031 events22 affected226 at risk EG00145 events22 affected225 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG00027 events23 affected226 at risk EG0018 events7 affected225 at risk
Hypothyroidism	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG00058 events48 affected226 at risk EG00122 events20 affected225 at risk
Dry eye	Eye disorders	MedDRA 26.0	Systematic Assessment	EG00015 events15 affected226 at risk EG0019 events9 affected225 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00017 events16 affected226 at risk EG00124 events22 affected225 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00028 events25 affected226 at risk EG00136 events29 affected225 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00095 events70 affected226 at risk EG00180 events61 affected225 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG000335 events146 affected226 at risk EG001278 events139 affected225 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00013 events13 affected226 at risk EG00115 events14 affected225 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00029 events27 affected226 at risk EG00142 events27 affected225 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00019 events12 affected226 at risk EG00117 events14 affected225 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00016 events16 affected226 at risk EG00115 events14 affected225 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG000323 events145 affected226 at risk EG001287 events139 affected225 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00068 events51 affected226 at risk EG00156 events46 affected225 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG000115 events78 affected226 at risk EG00189 events53 affected225 at risk
Asthenia	General disorders	MedDRA 26.0	Systematic Assessment	EG000193 events96 affected226 at risk EG001200 events87 affected225 at risk
Chills	General disorders	MedDRA 26.0	Systematic Assessment	EG0009 events9 affected226 at risk EG00116 events14 affected225 at risk
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG000107 events63 affected226 at risk EG00149 events38 affected225 at risk
Malaise	General disorders	MedDRA 26.0	Systematic Assessment	EG00021 events12 affected226 at risk EG00121 events16 affected225 at risk
Mucosal inflammation	General disorders	MedDRA 26.0	Systematic Assessment	EG00041 events32 affected226 at risk EG00142 events29 affected225 at risk
Oedema peripheral	General disorders	MedDRA 26.0	Systematic Assessment	EG00022 events15 affected226 at risk EG00117 events16 affected225 at risk
Pain	General disorders	MedDRA 26.0	Systematic Assessment	EG00020 events15 affected226 at risk EG00123 events17 affected225 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG00061 events44 affected226 at risk EG00173 events47 affected225 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0008 events8 affected226 at risk EG00114 events14 affected225 at risk
Conjunctivitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00016 events14 affected226 at risk EG00117 events17 affected225 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00021 events18 affected226 at risk EG00117 events15 affected225 at risk
Paronychia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00014 events14 affected226 at risk EG00116 events13 affected225 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00024 events20 affected226 at risk EG00122 events21 affected225 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00035 events25 affected226 at risk EG00131 events24 affected225 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG00057 events39 affected226 at risk EG00142 events33 affected225 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG00014 events14 affected226 at risk EG00119 events18 affected225 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG00054 events52 affected226 at risk EG00143 events42 affected225 at risk
Wound complication	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG00014 events13 affected226 at risk EG00116 events16 affected225 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG000138 events82 affected226 at risk EG00198 events65 affected225 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG000105 events69 affected226 at risk EG00178 events51 affected225 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG00014 events11 affected226 at risk EG00116 events14 affected225 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG00013 events12 affected226 at risk EG00110 events10 affected225 at risk
Ejection fraction decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00017 events17 affected226 at risk EG00126 events19 affected225 at risk
Lymphocyte count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00021 events13 affected226 at risk EG00120 events12 affected225 at risk
Neutrophil count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00069 events33 affected226 at risk EG00147 events29 affected225 at risk
Platelet count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00023 events17 affected226 at risk EG00119 events13 affected225 at risk
Weight decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00027 events26 affected226 at risk EG00117 events17 affected225 at risk
White blood cell count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG00025 events13 affected226 at risk EG00116 events10 affected225 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00062 events46 affected226 at risk EG00143 events35 affected225 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00016 events14 affected226 at risk EG0015 events4 affected225 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00016 events12 affected226 at risk EG00112 events10 affected225 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG00021 events12 affected226 at risk EG00122 events14 affected225 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00088 events59 affected226 at risk EG00179 events52 affected225 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00029 events23 affected226 at risk EG00121 events19 affected225 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00016 events15 affected226 at risk EG00122 events19 affected225 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00061 events45 affected226 at risk EG00166 events42 affected225 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00042 events27 affected226 at risk EG00131 events23 affected225 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00030 events23 affected226 at risk EG00130 events23 affected225 at risk
Dysgeusia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00037 events33 affected226 at risk EG00140 events35 affected225 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00082 events53 affected226 at risk EG00169 events50 affected225 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00017 events14 affected226 at risk EG00111 events9 affected225 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00050 events43 affected226 at risk EG00159 events45 affected225 at risk
Paraesthesia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00016 events15 affected226 at risk EG00125 events20 affected225 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00056 events47 affected226 at risk EG00145 events40 affected225 at risk
Polyneuropathy	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00019 events14 affected226 at risk EG00115 events13 affected225 at risk
Anxiety	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0009 events9 affected226 at risk EG00116 events14 affected225 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG00048 events39 affected226 at risk EG00136 events29 affected225 at risk
Dysuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG00023 events19 affected226 at risk EG00121 events17 affected225 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG00011 events11 affected226 at risk EG00116 events15 affected225 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00050 events39 affected226 at risk EG00165 events48 affected225 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00023 events19 affected226 at risk EG00133 events22 affected225 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00035 events32 affected226 at risk EG00138 events28 affected225 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00013 events12 affected226 at risk EG00114 events13 affected225 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00029 events25 affected226 at risk EG00118 events14 affected225 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG000158 events151 affected226 at risk EG001156 events146 affected225 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00024 events22 affected226 at risk EG00114 events13 affected225 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00025 events23 affected226 at risk EG00122 events21 affected225 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00020 events14 affected226 at risk EG00121 events17 affected225 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00017 events17 affected226 at risk EG00125 events25 affected225 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00020 events18 affected226 at risk EG00123 events22 affected225 at risk
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00016 events14 affected226 at risk EG0019 events6 affected225 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00042 events36 affected226 at risk EG00135 events25 affected225 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00096 events63 affected226 at risk EG00162 events49 affected225 at risk
Hot flush	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG00029 events25 affected226 at risk EG00128 events25 affected225 at risk
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG00022 events14 affected226 at risk EG00121 events13 affected225 at risk

Ancestor Terms

ID	Term
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D004224	Diterpenes
D013729	Terpenes
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D008453	Maytansine
D018942	Macrolides
D007783	Lactones
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds

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.

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
C000594389	atezolizumab
D004317	Doxorubicin
D003520	Cyclophosphamide
D017239	Paclitaxel
D000068878	Trastuzumab
C485206	pertuzumab
D000080044	Ado-Trastuzumab Emtansine