A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

Objective response rate (ORR) was defined as the percentage of participants with an objective response of complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) that have a reduction in short axis to < 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off to the nearest whole number.

PFS was defined as the time from randomization to the date of the first recorded occurrence of PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD 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 ≥ 5 mm. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for PFS.

CBR was defined as the percentage of participants with stable disease (SD) ≥ 24 weeks or with confirmed CR or PR, as determined by the investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target lesions and 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 SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD 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 ≥ 5 mm. Percentages have been rounded off to the nearest whole number.

OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier method was used to estimate the median for OS.

OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at Month 18. Percentages have been rounded off to the nearest whole number.

DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to the first date of recorded PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions and 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 SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum in study including baseline in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥ 5 mm. Participants who did not have documented PD or death, DOR was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for DOR.

An AE was any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

SAE = serious adverse events; AESIs = adverse events of special interest.

Nominal time restarted to 0 at Stage 2. PK data for Stage was analyzed and reported for the subgroups [crossover arms (Stage 1 to Stage 2)] only.

Nominal time restarted to 0 at Stage 2; RO5541267 = atezolizumab. PK data for Stage was analyzed and reported for the subgroups [crossover arms (Stage 1 to Stage 2)] only.

Participants who received atezolizumab 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 atezolizumab 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 (t.u.) 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 t.u. greater than the titer of the baseline sample (treatment unaffected). Participants with a positive post-baseline sample has been reported here.