A Study of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as Initial Treatment for Participants With Triple-Negative Breast Cancer That Has Spread

OR was defined as the rate of a PR or CR occurring after randomization and confirmed \>=28 days later as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.

Time frame: Randomization up to disease progression or relapse, whichever occurs first (up to approximately 5.25 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received.

PFS was defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, using RECIST v1.1. As per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.

Time frame: Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received. Data were only collected from participants in the Cohort I Expansion Stage (Cohort I: Cobimetinib, Paclitaxel, Cohort I: Placebo, Paclitaxel) for this outcome measure.

Time frame: Safety Run-In: Predose (Hr 0) on Cy 1 D8; predose (Hr 0), 0.5, 1, 2, 4, 6 Hr postdose on Cy1 D15; Expansion: predose (Hr 0), 1-4 Hr postdose on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug. Data were only collected from participants in the Cohort I: Safety Run-In stage for this outcome measure.

Time frame: Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 0.5, 1, 2, 4, and 6 Hr postdose (infusion duration: 1 Hr) on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug. Data were only collected from participants in the Cohort I: Safety Run-In stage for this outcome measure.

Time frame: Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 2, 4 Hr postdose (infusion duration: 30 minutes) on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug. Due to the sparse nature of PK sampling, the estimation of this PK parameter requires the use of population PK analysis. This would have enabled the exposure-response analysis with this OM. Given the outcome of the study, the Sponsors did not proceed with popPK analysis, which was planned, only if data warranted. AUC0-tau was not estimated and analyzed using the sparse PK samples.

Time frame: Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 2, 4 Hr postdose (infusion duration: 30 minutes) on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug

Time frame: Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 0.5, 1, 2, 4, and 6 Hr postdose (2, 4 Hr postdose for Cohort II) (infusion duration: 1 Hr) on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug. Data were only collected from Cohort I: Safety Run-In and Cohort II participants for this outcome measure.

Time frame: Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 2, 4 Hr postdose (infusion duration: 30 minutes) on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug

Time frame: Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 0.5, 1, 2, 4, and 6 Hr postdose (2, 4 Hr postdose for Cohort II) (infusion duration: 1 Hr) on Cy1 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug. Data were only collected from Cohort I: Safety Run-In and Cohort II participants for this outcome measure.

Time frame: Safety Run-In, Expansion: Predose (Hr 0), 0.5 Hr postdose (infusion duration: 1 Hr) on D1 of Cy1, 3; predose (Hr 0) on D1 of Cy2, 4, 8, every 8 Cy up to EOT (approximately 5.5 years); 120 days after EOT (approximately 5.5 years) (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug. Due to the sparse nature of PK sampling, the estimation of this PK parameter requires the use of population PK analysis. This would have enabled the exposure-response analysis with this OM. Given the outcome of the study, the Sponsors did not proceed with popPK analysis, which was planned, only if data warranted. AUC0-tau was not estimated and analyzed using the sparse PK samples.

Time frame: Safety Run-In, Expansion:Predose (Hr0), 0.5Hr postdose (infusion duration:1Hr) on D1 of Cy1, 3; predose (Hr0) on D1 of Cy2, 4, 8, every 8 Cy up to end of treatment (EOT); 120 days after EOT (approximately 5.25 years) (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug

Time frame: Safety Run-In, Expansion: Predose (Hr 0), 0.5 Hr postdose (infusion duration: 1 Hr) on D1 of Cy1, 3; predose (Hr 0) on D1 of Cy2, 4, 8, every 8 Cy up to EOT; 120 days after EOT (approximately 5.5 years) (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug

DOR was defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the investigator using RECIST v1.1 or death from any cause during the study, whichever occurred first.

Time frame: Time from the first occurrence of documented objective response to time of relapse or death, whichever occurs first (up to approximately 6.5 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received.

Time frame: Safety Run-In: Predose (Hour [Hr] 0) on Cycle (Cy) 1 Day (D) 8; predose (Hr 0), 0.5, 1, 2, 4, 6 Hr postdose (2, 4 Hr postdose for Cohorts II, III) on Cy1 D15; Expansion: predose (Hr 0), 1-4 Hr postdose on Cy1 D15; predose (Hr 0) on Cy2 D15 (Cy=28 days)

Population: The pharmacokinetic (PK) population included all participants with evaluable PK data who received at least one dose of study drug

Time frame: Safety Run-In: Predose (Hr 0) on Cy 1 D8; predose (Hr 0), 0.5, 1, 2, 4, 6 Hr postdose (2, 4 Hr postdose for Cohorts II, III) on Cy1 D15; Expansion: predose (Hr 0), 1-4 Hr postdose on Cy1 D15; predose (Hr 0) on Cy2 D15 (Cy=28 days)

Population: The PK population included all participants with evaluable PK data who received at least one dose of study drug

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

Time frame: Randomization up to death from any cause (up to approximately 6.5 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received. Data were only collected from participants in the Cohort I Expansion Stage (Cohort I: Cobimetinib, Paclitaxel, Cohort I: Placebo, Paclitaxel) along with the Cohort II and III for this outcome measure.

Time frame: Randomization up to end of study (up to approximately 6.5 years)

Population: Safety-evaluable population was defined as participants who received any amount of any study drug.

ORR\_uc (ORR confirmation not required) was defined as the rate of a PR or CR occurring after randomization as determined by the investigator using RECIST v1.1, confirmation not required. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.

Time frame: Randomization up to disease progression or relapse, whichever occurs fist (up to approximately 6.5 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received. Data were only collected from participants in the Cohort I Expansion Stage (Cohort I: Cobimetinib, Paclitaxel, Cohort I: Placebo, Paclitaxel) along with the Cohort II and III for this outcome measure.

PFS was defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, using RECIST v1.1. As per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Time frame: Randomization up to disease progression or relapse, whichever occurs first (up to approximately 6.5 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received.

OR was defined as the rate of a PR or CR occurring after randomization and confirmed \>=28 days later as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.

Time frame: Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)

Population: ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received. Data were only collected from participants in the Cohort I Expansion Stage (Cohort I: Cobimetinib, Paclitaxel, Cohort I: Placebo, Paclitaxel) for this outcome measure.