A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy

An adverse event is 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 adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Baseline up to study completion, approximately 40 months

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.

Time frame: Baseline up to approximately 15 months

Population: The intent-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.

Average post infusion atezolizumab concentration

Time frame: Pre-infusion (0 h), 30 min after EOI (over 60 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycles 2, 3, 8, and every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion/early discontinuation (approx. 40 months)

Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.

Average post infusion Deacetyl Mercapto 1-Oxopropyl Maytansine concentration of trastuzumab emtansine infusion

Time frame: Pre-infusion (0 h) on Day 1 Cycle 1 and 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4 (each cycle = 21 days)

Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.

Time frame: Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days)

Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.

Duration of OR was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.

Time frame: Baseline up to approximately 15 months

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants with OR were considered for duration of OR.

Average post infusion Trastuzumab Emtansine concentration

Time frame: Pre-infusion (0 hour [h]), 30 minutes (min) after end of infusion (EOI) (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days); at any time during study treatment/early discontinuation visit (approx. 40 months)

Population: PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.

OS was defined as the time from randomization to death from any cause.

Time frame: Baseline up to study completion or death, whichever occurs first, approximately 40 months

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.

ATAs are antibodies that inactivate the therapeutic effects of Atezolizumab. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).

Time frame: Pre-infusion (0 h) on Day 1 Cycles 1, 2, 3, 4, 8, and every 8 cycles thereafter (each cycle = 21 days) up to 120 days after treatment completion or early discontinuation (approximately 40 months)

Population: The analysis population included a patient with an ATA assay result from at least one post-baseline sample.

ATAs are antibodies that inactivate the therapeutic effects of Trastuzumab Emtansine. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).

Time frame: Pre-infusion (0 h) on Day 1 Cycles 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (approximately 40 months)

Population: The analysis population included a patient with an ATA assay result from at least one post-baseline sample

An OR was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be \< 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.

Time frame: Baseline up to approximately 15 months

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. In Participants with baseline measurable disease were considered for OR. In the atezolizumab arm, one patient was not ORR evaluable.