A Study of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo as a Treatment for Participants With Human Epidermal Growth Factor 2 (HER2)-Positive and Programmed Death-ligand 1 (PD-L1)-Positive Locally Advanced (LABC) or Metastatic Breast Cancer (MBC)

OS was defined as the time from the first dose of study treatment to the time of death from any cause. Participants who are alive as of the data cut-off date of the analysis were censored at the last known date they were alive. Participants with no post-baseline information were censored at the date of randomization plus 1 day. Median OS was calculated using the KM methodology.

Time frame: Up to 28 months

Population: ITT population included all participants who were randomized in the study, whether they received any study medication.

PFS was defined as the time from randomization to the first occurrence of documented disease progression (PD), as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Median PFS was calculated using the Kaplan-Meier (KM) methodology. Data for participants without PD or death from any cause as of the data cut-off date were censored at the time of the last tumor assessment.

Time frame: Up to 28 months

Population: ITT population included all participants who were randomized in the study, whether they received any study medication.

CNS PFS was defined as the time from randomization to the first occurrence of documented CNS PD, or first occurrence of symptomatic CNS disease as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology. Participants who experienced non-CNS PD at the time of analysis were censored at the date of this progression. Participants who experienced no PD and were alive at the time of analysis were censored at date of their last post-baseline tumor assessment or, if they had no post-baseline tumor assessment, on the date of randomization + 1 day.

Time frame: Up to 28 months

Population: ITT with CNS metastasis population included all participants in ITT with CNS metastasis at randomization.

CNS PFS was defined as the time from randomization to the first occurrence of documented CNS PD, or first occurrence of symptomatic CNS disease as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology. Participants who experienced non-CNS PD at the time of analysis were censored at the date of this progression. Participants who experienced no PD and were alive at the time of analysis were censored at date of their last post-baseline tumor assessment or, if they had no post-baseline tumor assessment, on the date of randomization + 1 day.

Time frame: Up to 28 months

Population: ITT without CNS metastases at baseline population included all participants in the ITT without CNS metastasis at baseline.

DOR was calculated for participants who had a best OR of CR/PR. DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median DOR was calculated using the KM methodology.

Time frame: Up to 28 months

Population: Subset ITT with measurable disease included all participants in the ITT with a measurable disease at baseline. ITT population included all participants who were randomized to the study, whether or not they received any study medication. Overall number analyzed is the number of participants with OR, i.e, responders.

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) on two consecutive assessments, at least 28 days apart, as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. Only participants with measurable disease at baseline were analyzed for this outcome measure. Participants without a post-baseline tumor assessment were considered non-responders. An estimate of the ORR and its 95% CI (Wilson score confidence interval) were calculated for each treatment arm.

Time frame: Up to 28 months

Population: Subset ITT with measurable disease included all participants in the ITT with a measurable disease at baseline. ITT population included all participants who were randomized to the study, whether or not they received any study medication.

OS is defined as the time from the first dose of study treatment to the time of death from any cause. Median OS was calculated using the KM methodology.

Time frame: Up to 28 months

Population: ITT with brain metastasis population included all participants in ITT with brain metastasis at randomization.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Time frame: Up to 28 months

Population: Safety evaluable population included all participants who received at least one full or partial dose of study drug. One participant randomized to Trastuzumab Emtansine + Placebo moved to Trastuzumab Emtansine + Atezolizumab 1200 mg. Hence, has been represented in the later arm for safety analysis.

PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology.

Time frame: Up to 28 months

Population: ITT with brain metastasis population included all participants in ITT with brain metastasis at randomization.

EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). The RF scale has 2 questions about work/daily activities and hobbies/leisurely activities. The PF and RF are scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL, functioning/support.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, the analysis for EORTC QLQ-C30 was not conducted.

As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, PK objectives and outcome measures were no longer applicable. Hence sample collection was stopped, and this outcome measure was not assessed or analyzed.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, PK objectives and outcome measures were no longer applicable. Hence sample collection was stopped, and this outcome measure was not assessed or analyzed.

As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, PK objectives and outcome measures were no longer applicable. Hence sample collection was stopped, and this outcome measure was not assessed or analyzed.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, PK objectives and outcome measures were no longer applicable. Hence sample collection was stopped, and this outcome measure was not assessed or analyzed.

EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). The RF scale has 2 questions about work/daily activities and hobbies/leisurely activities. The PF and RF are scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL, functioning/support.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, the analysis for EORTC QLQ-C30 was not conducted.

As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, immunogenicity objectives and outcome measures were no longer applicable.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, immunogenicity objectives and outcome measures were no longer applicable.

As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, immunogenicity objectives and outcome measures were no longer applicable.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, immunogenicity objectives and outcome measures were no longer applicable.

EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). The RF scale has 2 questions about work/daily activities and hobbies/leisurely activities. The PF and RF are scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL, functioning/support.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, the analysis for EORTC QLQ-C30 was not conducted.

PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the BICR committee according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: Up to 28 months

Population: As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, analysis of PFS as determined by a BICR committee was not conducted.