A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer (IPATunity130)

• ClinicalTrials.gov Identifier: NCT03337724
• Recruitment Status: Completed
• First Posted: November 9, 2017
• Results First Posted: March 12, 2024
• Last Update Posted: March 12, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Placebo
• Enrollment: 579

Participant Flow

Recruitment Details

Participants with protocol specified triple-negative breast cancer (TNBC) or HR+/HER- took part in the study in the following countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, Costa Rica, Czech Republic, France, Greece, Germany, Hungary, Italy, India, Japan, Macedonia, Mexico, Poland, Peru, Republic of Korea, Russian Federation, Slovenia, Spain, Singapore, South Africa, Taiwan, Turkey, Ukraine, United Kingdom, and United States from 6 January 2018 to 4 January 2023.

Pre-assignment Details

Participants with TNBC or hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-) breast adenocarcinoma with phosphatidylinositol-4,5-bisphosphate3-kinase,catalytic subunit, alpha(PIK3CA)/serine-threonine kinase(AKT1)/phosphatase & tensin homolog (PTEN)-altered tumor were randomized to ipatasertib 400 mg+paclitaxel or placebo+paclitaxel (Cohorts A,B) & those with TNBC without PIK3CA/ AKT1/PTEN-altered tumor received ipatasertib+atezolizumab+paclitaxel (Cohort C).

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 milligram per square meter (mg/m^2), intravenously (IV), on Days 1, 8, and 15 of each 28-day cycle and placebo, orally once a day (QD), on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Period Title: Overall Study
Started	87	168	76	146	102
Safety Evaluable Population [1]	87	166	75	145	102
Completed	0	0	0	0	0
Not Completed	87	168	76	146	102
Reason Not Completed
Reason not Specified	12	21	9	9	29
Withdrawal by Subject	13	15	4	15	6
Protocol Deviation	0	1	1	1	0
Adverse Event	1	1	0	1	0
Death	40	89	43	76	50
Lost to Follow-up	5	5	4	7	4
Physician Decision	16	34	14	34	13
Progressive Disease	0	2	1	2	0
Symptomatic Deterioration	0	0	0	1	0
[1] Safety Evaluable Population included all participants who received any amount of study treatment. Participants who were randomized (Cohorts A and B) or enrolled (Cohort C) into the study but who did not receive any study drug were not included in the Safety Evaluable Population.

Baseline Characteristics

Arm/Group Title		Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel	Total
Arm/Group Description		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.	Total of all reporting groups
Overall Number of Baseline Participants		87	168	76	146	102	579
Baseline Analysis Population Description		Intention-to-treat (ITT) Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	87 participants	168 participants	76 participants	146 participants	102 participants	579 participants
		54.2 (12.6)	54.6 (12.8)	54.5 (11.3)	57.2 (11.1)	54.6 (11.7)	55.2 (12.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	87 participants	168 participants	76 participants	146 participants	102 participants	579 participants
	Female	87 100.0%	167 99.4%	76 100.0%	144 98.6%	102 100.0%	576 99.5%
	Male	0 0.0%	1 0.6%	0 0.0%	2 1.4%	0 0.0%	3 0.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	87 participants	168 participants	76 participants	146 participants	102 participants	579 participants
	Hispanic or Latino	29 33.3%	59 35.1%	13 17.1%	29 19.9%	36 35.3%	166 28.7%
	Not Hispanic or Latino	57 65.5%	101 60.1%	62 81.6%	115 78.8%	58 56.9%	393 67.9%
	Unknown or Not Reported	1 1.1%	8 4.8%	1 1.3%	2 1.4%	8 7.8%	20 3.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	87 participants	168 participants	76 participants	146 participants	102 participants	579 participants
	American Indian or Alaska Native	13 14.9%	15 8.9%	3 3.9%	4 2.7%	5 4.9%	40 6.9%
	Asian	17 19.5%	37 22.0%	22 28.9%	38 26.0%	12 11.8%	126 21.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%	1 0.2%
	Black or African American	1 1.1%	5 3.0%	3 3.9%	2 1.4%	9 8.8%	20 3.5%
	White	51 58.6%	99 58.9%	45 59.2%	93 63.7%	55 53.9%	343 59.2%
	More than one race	0 0.0%	4 2.4%	2 2.6%	0 0.0%	5 4.9%	11 1.9%
	Unknown or Not Reported	5 5.7%	8 4.8%	1 1.3%	9 6.2%	15 14.7%	38 6.6%

Outcome Measures

1. Primary Outcome

Title	Cohort A: Progression-Free Survival (PFS)
Description	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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). The appearance of one or more new lesions was also considered progression.
Time Frame	From randomization up to 27 months

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in Cohorts A regardless of whether the participants received the assigned treatment.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.
Overall Number of Participants Analyzed	87	168
Median (95% Confidence Interval); Unit of Measure: months
	6.1; (5.5 to 9.0)	7.4; (5.6 to 8.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Placebo + Paclitaxel, Cohort A: Ipatasertib + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9237
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.45
	Estimation Comments	Stratification variables were: prior adjuvant/neoadjuvant chemotherapy (yes vs. no), region, tumor PIK3CA/AKT1/PTEN alteration status (PIK3CA/AKT1-activating mutations vs. PTEN alterations with no PIK3CA/AKT1-activating mutations).

2. Primary Outcome

Title	Cohort B: PFS
Description	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, 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 was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.
Time Frame	From randomization up to 24.4 months

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in Cohort B regardless of whether the participants received the assigned treatment.

Arm/Group Title	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed	76	146
Median (95% Confidence Interval); Unit of Measure: months
	9.3; (7.2 to 12.2)	9.3; (8.0 to 11.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort B: Placebo + Paclitaxel, Cohort B: Ipatasertib + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9965
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.40
	Estimation Comments	Stratification variables were: prior adjuvant/neoadjuvant chemotherapy (yes vs. no), region, prior therapy with a PI3K or mTOR inhibitor (yes vs. no).

3. Primary Outcome

Title	Cohort C: PFS
Description	PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, 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 was also considered progression.
Time Frame	From enrollment up to 31 months

Outcome Measure Data

Analysis Population Description

ITT population included of all enrolled participants in Cohort C.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	102
Median (95% Confidence Interval); Unit of Measure: months
	7.1; (5.5 to 9.1)

4. Secondary Outcome

Title	Cohort A and B: Objective Response Rate (ORR)
Description	ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Time Frame	From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. Overall number analyzed is the number of participants with measurable disease at baseline.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed	86	167	75	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	34.9; (24.92 to 45.92)	38.9; (31.49 to 46.76)	46.7; (35.05 to 58.55)	46.5; (38.18 to 55.02)

5. Secondary Outcome

Title	Cohort C: ORR
Description	ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was defined as 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Time Frame	From enrollment up to 31 months

Outcome Measure Data

Analysis Population Description

ITT population consisted of all enrolled participants in Cohort C.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	52.9; (42.80 to 62.90)

6. Secondary Outcome

Title	Cohort A and B: Duration of Response (DOR)
Description	DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, 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 was also considered progression.
Time Frame	From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. Overall number analyzed is the number of participants with objective response i.e., responders.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed	30	65	35	67
Median (95% Confidence Interval); Unit of Measure: months
	16.6 [1]; (4.9 to NA)	9.4; (7.3 to 11.1)	9.2; (6.8 to 12.5)	9.2; (7.2 to 11.3)

[1]

The upper limit of 95% confidence interval (CI) was not estimable due to insufficient number of participants with event.

7. Secondary Outcome

Title	Cohort C: DOR
Description	DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was defined as 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, 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 was also considered progression.
Time Frame	From enrollment up to 31 months

Outcome Measure Data

Analysis Population Description

ITT population consisted of all enrolled participants in Cohort C. Overall number analyzed is the number of participants with objective response i.e., responders.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	54
Median (95% Confidence Interval); Unit of Measure: months
	8.7; (5.7 to 12.7)

8. Secondary Outcome

Title	Cohort A and B: Clinical Benefit Rate (CBR)
Description	CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was defined as 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Time Frame	From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. Overall number analyzed is the number of participants with measurable disease at baseline.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed	86	167	75	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	45.3; (34.58 to 56.45)	46.7; (38.96 to 54.57)	65.3; (53.46 to 75.96)	68.8; (60.50 to 76.21)

9. Secondary Outcome

Title	Cohort C: CBR
Description	CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was defined as 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Time Frame	From enrollment up to 31 months

Outcome Measure Data

Analysis Population Description

ITT population consisted of all enrolled participants in Cohort C.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	54.9; (44.74 to 64.78)

10. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death from any cause.
Time Frame	From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	87	168	76	146	102
Median (95% Confidence Interval); Unit of Measure: months
	24.9; (16.9 to 40.4)	24.2; (19.2 to 29.4)	28.4; (20.6 to 37.3)	29.0; (22.4 to 34.8)	22.8 [1]; (17.8 to NA)

[1]

The upper limit of 95% CI was not estimable due to insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Placebo + Paclitaxel, Cohort A: Ipatasertib + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.58
	Estimation Comments	Stratification was done prior adjuvant/neoadjuvant chemotherapy (yes vs. no), region, tumor PIK3CA/AKT1/PTEN alteration status (PIK3CA/AKT1-activating mutations vs. PTEN alterations with no PIK3CA/AKT1-activating mutations).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort B: Placebo + Paclitaxel, Cohort B: Ipatasertib + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.37
	Estimation Comments	Stratification variables were: prior adjuvant/neoadjuvant chemotherapy (yes vs. no), region, prior therapy with a PI3K or mTOR inhibitor (yes vs. no).

11. Secondary Outcome

Title	Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Description	European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Time Frame	Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)

Outcome Measure Data

Analysis Population Description

Patient-reported outcome (PRO)-evaluable Population included all randomized (Cohorts A and B) participants who had a baseline and at least 1 postbaseline PRO assessment.Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed		79	160	73	146
Mean (Standard Deviation); Unit of Measure: score on scale
Day 1 Cycle 2	Number Analyzed	79 participants	160 participants	73 participants	127 participants
		0.95 (20.59)	-0.26 (24.58)	4.79 (15.83)	-3.61 (21.45)
Day 1 Cycle 3	Number Analyzed	72 participants	143 participants	70 participants	121 participants
		-0.93 (20.53)	0.35 (21.73)	1.19 (19.62)	-2.13 (17.99)
Day 1 Cycle 4	Number Analyzed	62 participants	124 participants	63 participants	113 participants
		-4.44 (19.42)	-2.42 (21.95)	-0.79 (21.10)	-1.99 (20.75)
Day 1 Cycle 5	Number Analyzed	56 participants	93 participants	56 participants	108 participants
		-2.08 (16.46)	-2.87 (18.61)	-1.19 (20.00)	-3.01 (18.70)
Day 1 Cycle 6	Number Analyzed	48 participants	77 participants	53 participants	101 participants
		-6.94 (15.97)	-2.06 (21.04)	1.42 (19.18)	-3.88 (20.67)
Day 1 Cycle 7	Number Analyzed	35 participants	61 participants	49 participants	94 participants
		-5.48 (12.45)	-3.28 (20.93)	0.34 (20.34)	-4.17 (19.47)
Day 1 Cycle 8	Number Analyzed	29 participants	51 participants	48 participants	89 participants
		-6.90 (13.56)	0.33 (22.11)	0.35 (16.84)	-5.99 (18.55)
Day 1 Cycle 9	Number Analyzed	22 participants	43 participants	38 participants	78 participants
		0.00 (10.29)	-3.49 (25.28)	1.10 (18.80)	-7.37 (20.05)
Day 1 Cycle 10	Number Analyzed	21 participants	35 participants	39 participants	70 participants
		-2.38 (9.91)	-4.52 (21.61)	1.28 (19.64)	-6.43 (18.83)
Day 1 Cycle 11	Number Analyzed	17 participants	28 participants	35 participants	65 participants
		-3.43 (15.88)	-4.46 (21.09)	2.38 (22.83)	-5.13 (19.30)
Day 1 Cycle 12	Number Analyzed	11 participants	23 participants	31 participants	58 participants
		0.76 (11.46)	-8.33 (19.94)	0.00 (22.46)	-4.02 (16.32)
Day 1 Cycle 13	Number Analyzed	8 participants	19 participants	24 participants	43 participants
		-5.21 (10.85)	-8.33 (23.57)	-2.43 (21.63)	-4.65 (18.57)
Day 1 Cycle 14	Number Analyzed	7 participants	14 participants	22 participants	38 participants
		-2.38 (10.45)	-3.57 (19.26)	-0.76 (21.81)	-3.29 (15.68)
Day 1 Cycle 15	Number Analyzed	6 participants	13 participants	15 participants	27 participants
		-9.72 (11.08)	-5.77 (12.90)	-2.22 (18.49)	-0.62 (20.14)
Day 1 Cycle 16	Number Analyzed	5 participants	11 participants	14 participants	25 participants
		-6.67 (13.69)	-8.33 (14.91)	-4.17 (19.27)	-2.33 (16.05)
Day 1 Cycle 17	Number Analyzed	4 participants	11 participants	12 participants	21 participants
		-8.33 (9.62)	-6.82 (13.34)	-7.64 (15.27)	-5.95 (13.73)
Day 1 Cycle 18	Number Analyzed	4 participants	7 participants	9 participants	14 participants
		-8.33 (9.62)	-15.48 (16.96)	-9.26 (19.74)	-6.55 (16.07)
Day 1 Cycle 19	Number Analyzed	4 participants	5 participants	5 participants	12 participants
		-4.17 (8.33)	-20.00 (7.45)	-11.67 (16.24)	-7.64 (23.96)
Day 1 Cycle 20	Number Analyzed	2 participants	3 participants	4 participants	10 participants
		-8.33 (11.79)	-5.56 (9.62)	-16.67 (11.79)	-10.00 (12.30)
Day 1 Cycle 21	Number Analyzed	1 participants	2 participants	3 participants	7 participants
		-16.67 [1] (NA)	-16.67 (0.00)	-13.89 (20.97)	-10.71 (13.36)
Day 1 Cycle 22	Number Analyzed	1 participants	1 participants	3 participants	7 participants
		-16.67 [1] (NA)	-16.67 [1] (NA)	-11.11 (9.62)	-14.29 (15.00)
Day 1 Cycle 23	Number Analyzed	1 participants	1 participants	3 participants	5 participants
		-16.67 [1] (NA)	-25.00 [1] (NA)	-16.67 (16.67)	-15.00 (18.07)
Day 1 Cycle 24	Number Analyzed	1 participants	1 participants	2 participants	2 participants
		-16.67 [1] (NA)	-41.67 [1] (NA)	-16.67 (0.00)	-16.67 (11.79)

[1]

The standard deviation was not estimable for a single participant.

12. Secondary Outcome

Title	Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Description	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Time Frame	Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)

Outcome Measure Data

Analysis Population Description

PRO-evaluable Population for Cohort C included all enrolled participants who had a baseline and at least 1 postbaseline PRO assessment.Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: score on scale
Day 1 Cycle 2	Number Analyzed	100 participants
		-0.42 (18.02)
Day 1 Cycle 3	Number Analyzed	92 participants
		0.18 (18.32)
Day 1 Cycle 4	Number Analyzed	84 participants
		-4.37 (22.83)
Day 1 Cycle 5	Number Analyzed	65 participants
		-6.41 (20.19)
Day 1 Cycle 6	Number Analyzed	61 participants
		-7.10 (21.24)
Day 1 Cycle 7	Number Analyzed	54 participants
		-5.09 (18.20)
Day 1 Cycle 8	Number Analyzed	50 participants
		-4.83 (21.24)
Day 1 Cycle 9	Number Analyzed	37 participants
		-7.66 (23.68)
Day 1 Cycle 10	Number Analyzed	33 participants
		-7.07 (18.76)
Day 1 Cycle 11	Number Analyzed	25 participants
		-6.00 (19.02)
Day 1 Cycle 12	Number Analyzed	23 participants
		-2.90 (18.57)
Day 1 Cycle 13	Number Analyzed	23 participants
		-1.45 (19.08)
Day 1 Cycle 14	Number Analyzed	19 participants
		-7.89 (21.24)
Day 1 Cycle 15	Number Analyzed	18 participants
		-5.09 (26.37)
Day 1 Cycle 16	Number Analyzed	16 participants
		-11.98 (27.55)
Day 1 Cycle 17	Number Analyzed	13 participants
		-10.90 (32.16)
Day 1 Cycle 18	Number Analyzed	13 participants
		-3.85 (20.30)
Day 1 Cycle 19	Number Analyzed	13 participants
		-3.21 (25.35)
Day 1 Cycle 20	Number Analyzed	13 participants
		-3.21 (24.89)
Day 1 Cycle 21	Number Analyzed	13 participants
		-2.56 (24.86)
Day 1 Cycle 22	Number Analyzed	13 participants
		-12.18 (32.92)
Day 1 Cycle 23	Number Analyzed	11 participants
		3.03 (24.23)
Day 1 Cycle 24	Number Analyzed	11 participants
		3.79 (24.54)
Day 1 Cycle 25	Number Analyzed	9 participants
		-4.63 (21.29)
Day 1 Cycle 26	Number Analyzed	10 participants
		-0.83 (19.82)
Day 1 Cycle 27	Number Analyzed	8 participants
		2.08 (26.63)
Day 1 Cycle 28	Number Analyzed	6 participants
		1.39 (23.81)
Day 1 Cycle 29	Number Analyzed	7 participants
		-1.19 (28.64)
Day 1 Cycle 30	Number Analyzed	5 participants
		3.33 (24.01)
Day 1 Cycle 31	Number Analyzed	3 participants
		22.22 (12.73)
Day 1 Cycle 32	Number Analyzed	4 participants
		10.42 (23.94)
Day 1 Cycle 33	Number Analyzed	3 participants
		16.67 (22.05)
Day 1 Cycle 34	Number Analyzed	3 participants
		16.67 (30.05)
Day 1 Cycle 35	Number Analyzed	3 participants
		13.89 (17.35)
Day 1 Cycle 36	Number Analyzed	2 participants
		20.83 (29.46)
Day 1 Cycle 37	Number Analyzed	2 participants
		16.67 (23.57)
Day 1 Cycle 38	Number Analyzed	2 participants
		16.67 (23.57)
Day 1 Cycle 39	Number Analyzed	2 participants
		25.00 (35.36)
Day 1 Cycle 40	Number Analyzed	1 participants
		33.33 [1] (NA)
Day 1 Cycle 41	Number Analyzed	1 participants
		50.00 [1] (NA)
Day 1 Cycle 42	Number Analyzed	1 participants
		41.67 [1] (NA)
Day 1 Cycle 43	Number Analyzed	1 participants
		41.67 [1] (NA)
Day 1 Cycle 44	Number Analyzed	1 participants
		50.00 [1] (NA)

[1]

The standard deviation was not estimable for a single participant.

13. Secondary Outcome

Title	Cohort B: Time to Deterioration (TTD) in Pain
Description	Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed ≥ 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.
Time Frame	Baseline up to 24.4 months

Outcome Measure Data

Analysis Population Description

ITT Population for Cohort B included as all randomized participants regardless of whether the participants received the assigned treatment.

Arm/Group Title	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed	76	146
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [2]; (11.1 to NA)

[1]

Median and 95% CI were not estimable due to insufficient number of participants with events.

[2]

Median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort B: Placebo + Paclitaxel, Cohort B: Ipatasertib + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2162
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.83 to 2.22
	Estimation Comments	Stratification variables were: prior adjuvant/neoadjuvant chemotherapy (yes vs. no), region, prior therapy with a PI3K or mTOR inhibitor (yes vs. no).
Other Statistical Analysis		Stratified Analysis

14. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE 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. AEs were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Time Frame	Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population included all participants who received any amount of study treatment.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	87	166	75	145	102
Measure Type: Count of Participants; Unit of Measure: Participants
	84 96.6%	162 97.6%	74 98.7%	144 99.3%	102 100.0%

15. Secondary Outcome

Title	Number of Participants With at Least One Adverse Events of Special Interest (AESI)
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE 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. AEs were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade >= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade >= 2 colitis/enterocolitis.
Time Frame	Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population included all participants who received any amount of study treatment.

Arm/Group Title	Cohort A: Placebo + Paclitaxel	Cohort A: Ipatasertib + Paclitaxel	Cohort B: Placebo + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	87	166	75	145	102
Measure Type: Count of Participants; Unit of Measure: Participants
	79 90.8%	157 94.6%	73 97.3%	141 97.2%	101 99.0%

16. Secondary Outcome

Title	Cohorts A and B:Plasma Concentration of Ipatasertib
Description	[Not Specified]
Time Frame	Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)

Outcome Measure Data

Analysis Population Description

PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort A: Ipatasertib + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed		146	132
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms per milliliter (ng/mL)
Cycle 1 Day 1	Number Analyzed	146 participants	132 participants
		176; (232%)	165; (326%)
Cycle 1 Day 15	Number Analyzed	132 participants	119 participants
		191; (184%)	211; (216%)
Cycle 3 Day 15	Number Analyzed	110 participants	102 participants
		165; (169%)	234; (149%)

17. Secondary Outcome

Title	Cohort C: Plasma Concentration of Ipatasertib
Description	[Not Specified]
Time Frame	Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)

Outcome Measure Data

Analysis Population Description

PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed		94
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Cycle 1 Day 1	Number Analyzed	94 participants
		175; (183%)
Cycle 1 Day 15	Number Analyzed	82 participants
		233; (161.6%)
Cycle 3 Day 15	Number Analyzed	62 participants
		207; (197.6%)

18. Secondary Outcome

Title	Cohorts A and B: Plasma Concentration of G-037720
Description	G-037720 was a metabolite of ipatasertib.
Time Frame	Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )

Outcome Measure Data

Analysis Population Description

PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort A: Ipatasertib + Paclitaxel	Cohort B: Ipatasertib + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.	Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.
Overall Number of Participants Analyzed		146	123
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Cycle 1 Day 1	Number Analyzed	146 participants	123 participants
		45.6; (777%)	68.2; (405%)
Cycle 1 Day 15	Number Analyzed	132 participants	119 participants
		83.9; (183%)	95.1; (211%)
Cycle 3 Day 15	Number Analyzed	110 participants	102 participants
		90.8; (180%)	109; (169%)

19. Secondary Outcome

Title	Cohort C: Plasma Concentration of G-037720
Description	G-037720 was a metabolite of ipatasertib.
Time Frame	Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )

Outcome Measure Data

Analysis Population Description

PK Evaluable Population included all participants who had at least one evaluable plasma sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed		91
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Cycle 1 Day 1	Number Analyzed	91 participants
		67.3; (222.3%)
Cycle 1 Day 15	Number Analyzed	82 participants
		96.8; (140.7%)
Cycle 3 Day 15	Number Analyzed	62 participants
		96.5; (167.9%)

20. Secondary Outcome

Title	Cohort C: 1-year Event-free PFS Rate
Description	PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, 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 was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Time Frame	From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year

Outcome Measure Data

Analysis Population Description

ITT Population for Cohort C included all enrolled participants in Cohort C.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	31.17; (21.59 to 40.76)

21. Secondary Outcome

Title	Cohort C: 1-year Event-free OS Rate
Description	OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.
Time Frame	From enrollment up to death from any cause, up to 1 year

Outcome Measure Data

Analysis Population Description

ITT Population for Cohort C included all enrolled participants in Cohort C.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	79.38; (71.31 to 87.44)

22. Secondary Outcome

Title	Cohort C: Serum Concentration of Atezolizumab
Description	As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Time Frame	Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)

Outcome Measure Data

Analysis Population Description

For Cohort C, PK Evaluable Population included all participants who had at least one evaluable plasma sample in Cohort C. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.

Arm/Group Title		Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed		101
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: micrograms per milliliter (µg/mL)
Day 1 Cycle 1	Number Analyzed	84 participants
		309; (31.7%)
Day 15 Cycle 1	Number Analyzed	78 participants
		91.5; (23.9%)
Day 1 Cycle 2	Number Analyzed	92 participants
		130; (54.1%)
Day 1 Cycle 3	Number Analyzed	84 participants
		200; (41.1%)
Day 1 Cycle 4	Number Analyzed	80 participants
		231; (52.3%)
Day 1 Cycle 8	Number Analyzed	46 participants
		327; (27.6%)
Day 1 Cycle 12	Number Analyzed	21 participants
		371; (30.5%)
Day 1 Cycle 16	Number Analyzed	12 participants
		402; (42.4%)

23. Secondary Outcome

Title	Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Description	The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Time Frame	Up to 45.5 months

Outcome Measure Data

Analysis Population Description

For Cohort C, Safety Evaluable Population included all participants who received any amount of study treatment in cohort C. Overall number analyzed is the number of participants with an ADA assay result from at least one post-baseline sample.

Arm/Group Title	Cohort C: Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description:	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
Overall Number of Participants Analyzed	101
Measure Type: Count of Participants; Unit of Measure: Participants
	18 17.8%

Adverse Events

Time Frame	Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Adverse Event Reporting Description	All-cause Mortality: ITT Population included all randomized participants in Cohorts A and B regardless of whether the participants received the assigned treatment. For Cohort C, the ITT population consisted of all enrolled participants in Cohort C. Serious and Other Adverse Events: Safety Evaluable Population included all participants who received any amount of study treatment.
Arm/Group Title	COHORT A Placebo + Paclitaxel		COHORT A Ipatasertib + Paclitaxel		COHORT B Placebo + Paclitaxel		COHORT B Ipatasertib + Paclitaxel		COHORT C Ipatasertib + Atezolizumab + Paclitaxel
Arm/Group Description	Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 58.9 months.		Participants with histologically confirmed HR+ /HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and placebo, orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.		Participants with histologically confirmed HR+/HER2- adenocarcinoma of the breast with PIK3CA/AKT1/PTEN alteration and no prior systemic chemotherapy in the advanced disease setting and who were candidates for taxane monotherapy received paclitaxel chemotherapy, 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle up to 59.9 months.		Participants with histologically confirmed locally advanced unresectable or metastatic TNBC without PIK3CA/AKT1/PTEN-altered tumors and no prior systemic chemotherapy in the advanced disease setting received paclitaxel chemotherapy 80 mg/m^2, IV, on Days 1, 8, and 15 of each 28-day cycle, ipatasertib at a dose of 400 mg, administered orally QD, on Days 1 to 21 of each 28-day cycle, and atezolizumab 840 mg, IV, on Days 1 and 15 of each 28-day cycle up to 45.5 months.
All-Cause Mortality
	COHORT A Placebo + Paclitaxel		COHORT A Ipatasertib + Paclitaxel		COHORT B Placebo + Paclitaxel		COHORT B Ipatasertib + Paclitaxel		COHORT C Ipatasertib + Atezolizumab + Paclitaxel
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	41/87 (47.13%)		91/168 (54.17%)		44/76 (57.89%)		78/146 (53.42%)		50/102 (49.02%)
Serious Adverse Events
	COHORT A Placebo + Paclitaxel		COHORT A Ipatasertib + Paclitaxel		COHORT B Placebo + Paclitaxel		COHORT B Ipatasertib + Paclitaxel		COHORT C Ipatasertib + Atezolizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/87 (22.99%)		34/166 (20.48%)		11/75 (14.67%)		30/145 (20.69%)		29/102 (28.43%)
Blood and lymphatic system disorders
Anaemia † 1	1/87 (1.15%)	1	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Febrile neutropenia † 1	0/87 (0.00%)	0	3/166 (1.81%)	3	0/75 (0.00%)	0	2/145 (1.38%)	2	2/102 (1.96%)	2
Leukopenia † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	0/102 (0.00%)	0
Neutropenia † 1	1/87 (1.15%)	1	1/166 (0.60%)	1	0/75 (0.00%)	0	2/145 (1.38%)	2	0/102 (0.00%)	0
Thrombocytopenia † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Cardiac arrest † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Cardiopulmonary failure † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Myocarditis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Sinus tachycardia † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Eye disorders
Epiretinal membrane † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Eyelid oedema † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Glaucoma † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Macular oedema † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Gastrointestinal disorders
Abdominal hernia † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Abdominal pain † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Chronic gastritis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Colitis † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Diarrhoea † 1	0/87 (0.00%)	0	6/166 (3.61%)	8	1/75 (1.33%)	1	4/145 (2.76%)	5	4/102 (3.92%)	4
Enterocolitis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Intestinal obstruction † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Large intestine perforation † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Nausea † 1	0/87 (0.00%)	0	2/166 (1.20%)	2	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Upper gastrointestinal haemorrhage † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Vomiting † 1	0/87 (0.00%)	0	2/166 (1.20%)	2	0/75 (0.00%)	0	0/145 (0.00%)	0	2/102 (1.96%)	2
General disorders
Death † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Extravasation † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Fatigue † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	1/75 (1.33%)	1	0/145 (0.00%)	0	2/102 (1.96%)	2
General physical health deterioration † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	1/102 (0.98%)	1
Hyperthermia † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Pyrexia † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	4/102 (3.92%)	4
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Cholecystitis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	2/102 (1.96%)	2
Cholecystitis acute † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	1/145 (0.69%)	1	0/102 (0.00%)	0
Hypertransaminasaemia † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Immune system disorders
Hypersensitivity † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	1/102 (0.98%)	1
Infections and infestations
Abdominal abscess † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Abscess jaw † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
COVID-19 † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	1/102 (0.98%)	1
COVID-19 pneumonia † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Cellulitis † 1	1/87 (1.15%)	2	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Emphysematous cystitis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Erysipelas † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Gastroenteritis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Gastroenteritis norovirus † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Influenza † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Lower respiratory tract infection † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Peritonitis † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Pneumonia † 1	4/87 (4.60%)	4	2/166 (1.20%)	2	1/75 (1.33%)	1	2/145 (1.38%)	2	3/102 (2.94%)	3
Sepsis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	0/102 (0.00%)	0
Skin infection † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Suspected COVID-19 † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Upper respiratory tract infection † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	0/102 (0.00%)	0
Urinary tract infection † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	1/75 (1.33%)	1	0/145 (0.00%)	0	3/102 (2.94%)	3
Viral infection † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Wound infection † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	0/102 (0.00%)	0
Injury, poisoning and procedural complications
Femur fracture † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	0/102 (0.00%)	0
Fracture † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Procedural pain † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Road traffic accident † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Skin laceration † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Spinal fracture † 1	1/87 (1.15%)	1	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Aspartate aminotransferase increased † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Blood creatine phosphokinase increased † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Lymphocyte count decreased † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	2	0/102 (0.00%)	0
Dehydration † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	2/102 (1.96%)	2
Diabetic ketoacidosis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Hyperglycaemia † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Hypoglycaemia † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Tumour lysis syndrome † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc compression † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Musculoskeletal chest pain † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Myositis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Pathological fracture † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Infected neoplasm † 1	1/87 (1.15%)	2	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Lymphangiosis carcinomatosa † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Schwannoma † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Tumour fistulisation † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Tumour haemorrhage † 1	0/87 (0.00%)	0	1/166 (0.60%)	2	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Tumour necrosis † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	1/75 (1.33%)	1	0/145 (0.00%)	0	2/102 (1.96%)	2
Nervous system disorders
Cerebrovascular accident † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Dystonia † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Posterior reversible encephalopathy syndrome † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Psychiatric disorders
Anxiety † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	1/102 (0.98%)	1
Hydronephrosis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	1/75 (1.33%)	1	0/145 (0.00%)	0	0/102 (0.00%)	0
Renal impairment † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/87 (1.15%)	1	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Haemoptysis † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Immune-mediated lung disease † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Pleural effusion † 1	2/87 (2.30%)	2	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	1/102 (0.98%)	1
Pneumonitis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	2/145 (1.38%)	2	2/102 (1.96%)	2
Pneumothorax † 1	1/87 (1.15%)	1	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	0/102 (0.00%)	0
Pulmonary embolism † 1	0/87 (0.00%)	0	3/166 (1.81%)	3	1/75 (1.33%)	1	0/145 (0.00%)	0	1/102 (0.98%)	1
Respiratory distress † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	0/87 (0.00%)	0	1/166 (0.60%)	1	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Rash † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	2/102 (1.96%)	2
Vascular disorders
Deep vein thrombosis † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	1/145 (0.69%)	1	0/102 (0.00%)	0
Lymphoedema † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	COHORT A Placebo + Paclitaxel		COHORT A Ipatasertib + Paclitaxel		COHORT B Placebo + Paclitaxel		COHORT B Ipatasertib + Paclitaxel		COHORT C Ipatasertib + Atezolizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/87 (94.25%)		161/166 (96.99%)		72/75 (96.00%)		141/145 (97.24%)		101/102 (99.02%)
Blood and lymphatic system disorders
Anaemia † 1	23/87 (26.44%)	34	43/166 (25.90%)	58	15/75 (20.00%)	28	45/145 (31.03%)	57	34/102 (33.33%)	50
Leukopenia † 1	4/87 (4.60%)	11	7/166 (4.22%)	23	7/75 (9.33%)	16	8/145 (5.52%)	18	11/102 (10.78%)	49
Neutropenia † 1	20/87 (22.99%)	39	28/166 (16.87%)	92	18/75 (24.00%)	58	36/145 (24.83%)	95	25/102 (24.51%)	114
Ear and labyrinth disorders
Vertigo † 1	1/87 (1.15%)	1	9/166 (5.42%)	11	2/75 (2.67%)	2	4/145 (2.76%)	4	2/102 (1.96%)	2
Endocrine disorders
Hypothyroidism † 1	0/87 (0.00%)	0	0/166 (0.00%)	0	0/75 (0.00%)	0	0/145 (0.00%)	0	6/102 (5.88%)	6
Gastrointestinal disorders
Abdominal pain † 1	5/87 (5.75%)	6	15/166 (9.04%)	16	7/75 (9.33%)	9	11/145 (7.59%)	17	12/102 (11.76%)	13
Abdominal pain upper † 1	8/87 (9.20%)	10	16/166 (9.64%)	16	5/75 (6.67%)	7	15/145 (10.34%)	21	6/102 (5.88%)	6
Constipation † 1	31/87 (35.63%)	40	49/166 (29.52%)	56	26/75 (34.67%)	33	42/145 (28.97%)	54	13/102 (12.75%)	20
Diarrhoea † 1	28/87 (32.18%)	56	138/166 (83.13%)	477	29/75 (38.67%)	64	125/145 (86.21%)	461	86/102 (84.31%)	324
Dyspepsia † 1	4/87 (4.60%)	4	14/166 (8.43%)	18	4/75 (5.33%)	6	9/145 (6.21%)	11	6/102 (5.88%)	7
Flatulence † 1	1/87 (1.15%)	1	5/166 (3.01%)	6	4/75 (5.33%)	6	7/145 (4.83%)	7	3/102 (2.94%)	3
Gastrooesophageal reflux disease † 1	0/87 (0.00%)	0	4/166 (2.41%)	5	4/75 (5.33%)	4	4/145 (2.76%)	5	5/102 (4.90%)	5
Nausea † 1	22/87 (25.29%)	29	66/166 (39.76%)	106	17/75 (22.67%)	28	60/145 (41.38%)	94	42/102 (41.18%)	65
Stomatitis † 1	6/87 (6.90%)	12	18/166 (10.84%)	31	6/75 (8.00%)	8	16/145 (11.03%)	27	7/102 (6.86%)	8
Vomiting † 1	8/87 (9.20%)	10	53/166 (31.93%)	112	6/75 (8.00%)	10	45/145 (31.03%)	67	28/102 (27.45%)	43
General disorders
Asthenia † 1	10/87 (11.49%)	12	35/166 (21.08%)	40	13/75 (17.33%)	17	27/145 (18.62%)	36	19/102 (18.63%)	22
Fatigue † 1	15/87 (17.24%)	16	30/166 (18.07%)	33	19/75 (25.33%)	30	29/145 (20.00%)	36	23/102 (22.55%)	35
Mucosal inflammation † 1	2/87 (2.30%)	4	11/166 (6.63%)	13	3/75 (4.00%)	4	8/145 (5.52%)	11	12/102 (11.76%)	12
Oedema † 1	2/87 (2.30%)	2	5/166 (3.01%)	5	4/75 (5.33%)	4	9/145 (6.21%)	10	3/102 (2.94%)	3
Oedema peripheral † 1	7/87 (8.05%)	7	18/166 (10.84%)	23	14/75 (18.67%)	19	21/145 (14.48%)	28	7/102 (6.86%)	9
Pyrexia † 1	6/87 (6.90%)	6	16/166 (9.64%)	17	4/75 (5.33%)	5	23/145 (15.86%)	30	9/102 (8.82%)	13
Hepatobiliary disorders
Hyperbilirubinaemia † 1	3/87 (3.45%)	12	0/166 (0.00%)	0	4/75 (5.33%)	38	6/145 (4.14%)	12	6/102 (5.88%)	13
Immune system disorders
Hypersensitivity † 1	5/87 (5.75%)	5	4/166 (2.41%)	8	0/75 (0.00%)	0	0/145 (0.00%)	0	1/102 (0.98%)	1
Infections and infestations
Cystitis † 1	3/87 (3.45%)	5	8/166 (4.82%)	9	6/75 (8.00%)	9	7/145 (4.83%)	12	2/102 (1.96%)	2
Nasopharyngitis † 1	3/87 (3.45%)	4	11/166 (6.63%)	16	7/75 (9.33%)	11	19/145 (13.10%)	24	5/102 (4.90%)	5
Upper respiratory tract infection † 1	3/87 (3.45%)	3	12/166 (7.23%)	13	6/75 (8.00%)	7	14/145 (9.66%)	19	8/102 (7.84%)	10
Urinary tract infection † 1	2/87 (2.30%)	3	12/166 (7.23%)	16	4/75 (5.33%)	7	16/145 (11.03%)	18	7/102 (6.86%)	9
Injury, poisoning and procedural complications
Accidental overdose † 1	3/87 (3.45%)	8	6/166 (3.61%)	6	1/75 (1.33%)	1	6/145 (4.14%)	6	6/102 (5.88%)	12
Investigations
Alanine aminotransferase increased † 1	7/87 (8.05%)	16	23/166 (13.86%)	29	15/75 (20.00%)	30	19/145 (13.10%)	27	25/102 (24.51%)	59
Aspartate aminotransferase increased † 1	6/87 (6.90%)	7	18/166 (10.84%)	23	10/75 (13.33%)	16	13/145 (8.97%)	18	21/102 (20.59%)	39
Blood alkaline phosphatase increased † 1	1/87 (1.15%)	1	9/166 (5.42%)	12	7/75 (9.33%)	9	3/145 (2.07%)	4	12/102 (11.76%)	20
Blood lactate dehydrogenase increased † 1	4/87 (4.60%)	4	7/166 (4.22%)	9	8/75 (10.67%)	11	5/145 (3.45%)	7	7/102 (6.86%)	10
Neutrophil count decreased † 1	10/87 (11.49%)	23	22/166 (13.25%)	49	18/75 (24.00%)	65	23/145 (15.86%)	94	8/102 (7.84%)	33
Weight decreased † 1	3/87 (3.45%)	3	12/166 (7.23%)	13	2/75 (2.67%)	2	7/145 (4.83%)	8	7/102 (6.86%)	7
Weight increased † 1	1/87 (1.15%)	4	3/166 (1.81%)	4	3/75 (4.00%)	3	0/145 (0.00%)	0	6/102 (5.88%)	6
White blood cell count decreased † 1	7/87 (8.05%)	15	11/166 (6.63%)	28	5/75 (6.67%)	27	10/145 (6.90%)	44	5/102 (4.90%)	10
Metabolism and nutrition disorders
Decreased appetite † 1	10/87 (11.49%)	10	29/166 (17.47%)	35	7/75 (9.33%)	15	21/145 (14.48%)	29	14/102 (13.73%)	15
Hyperglycaemia † 1	9/87 (10.34%)	16	31/166 (18.67%)	49	10/75 (13.33%)	39	19/145 (13.10%)	27	22/102 (21.57%)	42
Hypertriglyceridaemia † 1	2/87 (2.30%)	2	9/166 (5.42%)	11	5/75 (6.67%)	8	7/145 (4.83%)	8	4/102 (3.92%)	5
Hypokalaemia † 1	3/87 (3.45%)	3	5/166 (3.01%)	6	2/75 (2.67%)	2	6/145 (4.14%)	8	8/102 (7.84%)	10
Musculoskeletal and connective tissue disorders
Arthralgia † 1	12/87 (13.79%)	18	16/166 (9.64%)	24	10/75 (13.33%)	16	26/145 (17.93%)	40	13/102 (12.75%)	19
Back pain † 1	9/87 (10.34%)	14	16/166 (9.64%)	21	7/75 (9.33%)	8	21/145 (14.48%)	25	10/102 (9.80%)	11
Bone pain † 1	0/87 (0.00%)	0	7/166 (4.22%)	9	4/75 (5.33%)	4	9/145 (6.21%)	17	2/102 (1.96%)	2
Muscle spasms † 1	1/87 (1.15%)	1	4/166 (2.41%)	4	5/75 (6.67%)	6	3/145 (2.07%)	5	5/102 (4.90%)	5
Myalgia † 1	5/87 (5.75%)	5	16/166 (9.64%)	24	9/75 (12.00%)	12	15/145 (10.34%)	17	10/102 (9.80%)	14
Pain in extremity † 1	4/87 (4.60%)	5	14/166 (8.43%)	18	6/75 (8.00%)	6	13/145 (8.97%)	24	4/102 (3.92%)	5
Nervous system disorders
Dizziness † 1	8/87 (9.20%)	8	6/166 (3.61%)	8	3/75 (4.00%)	4	10/145 (6.90%)	12	10/102 (9.80%)	14
Dysgeusia † 1	8/87 (9.20%)	8	10/166 (6.02%)	11	4/75 (5.33%)	4	11/145 (7.59%)	12	6/102 (5.88%)	6
Headache † 1	10/87 (11.49%)	19	28/166 (16.87%)	56	8/75 (10.67%)	19	24/145 (16.55%)	37	21/102 (20.59%)	33
Neuropathy peripheral † 1	20/87 (22.99%)	23	39/166 (23.49%)	49	12/75 (16.00%)	15	46/145 (31.72%)	63	30/102 (29.41%)	41
Paraesthesia † 1	2/87 (2.30%)	3	8/166 (4.82%)	11	6/75 (8.00%)	8	13/145 (8.97%)	14	5/102 (4.90%)	7
Peripheral sensory neuropathy † 1	19/87 (21.84%)	19	32/166 (19.28%)	38	23/75 (30.67%)	24	23/145 (15.86%)	30	8/102 (7.84%)	8
Polyneuropathy † 1	7/87 (8.05%)	7	5/166 (3.01%)	5	6/75 (8.00%)	6	12/145 (8.28%)	13	8/102 (7.84%)	8
Psychiatric disorders
Insomnia † 1	5/87 (5.75%)	6	10/166 (6.02%)	11	6/75 (8.00%)	6	6/145 (4.14%)	7	10/102 (9.80%)	10
Reproductive system and breast disorders
Breast pain † 1	3/87 (3.45%)	3	9/166 (5.42%)	11	0/75 (0.00%)	0	3/145 (2.07%)	3	4/102 (3.92%)	5
Respiratory, thoracic and mediastinal disorders
Cough † 1	10/87 (11.49%)	11	14/166 (8.43%)	15	6/75 (8.00%)	6	23/145 (15.86%)	32	16/102 (15.69%)	18
Dyspnoea † 1	7/87 (8.05%)	9	7/166 (4.22%)	10	2/75 (2.67%)	2	10/145 (6.90%)	13	9/102 (8.82%)	11
Epistaxis † 1	3/87 (3.45%)	5	12/166 (7.23%)	14	4/75 (5.33%)	4	15/145 (10.34%)	17	8/102 (7.84%)	10
Oropharyngeal pain † 1	0/87 (0.00%)	0	13/166 (7.83%)	18	2/75 (2.67%)	3	11/145 (7.59%)	15	6/102 (5.88%)	8
Skin and subcutaneous tissue disorders
Alopecia † 1	38/87 (43.68%)	39	78/166 (46.99%)	80	44/75 (58.67%)	46	75/145 (51.72%)	79	42/102 (41.18%)	42
Dry skin † 1	4/87 (4.60%)	5	0/166 (0.00%)	0	5/75 (6.67%)	6	5/145 (3.45%)	5	1/102 (0.98%)	1
Erythema † 1	5/87 (5.75%)	6	3/166 (1.81%)	3	3/75 (4.00%)	4	5/145 (3.45%)	5	3/102 (2.94%)	3
Nail discolouration † 1	4/87 (4.60%)	4	6/166 (3.61%)	7	8/75 (10.67%)	8	9/145 (6.21%)	9	1/102 (0.98%)	1
Pruritus † 1	7/87 (8.05%)	8	15/166 (9.04%)	21	3/75 (4.00%)	5	15/145 (10.34%)	25	17/102 (16.67%)	24
Rash † 1	11/87 (12.64%)	13	26/166 (15.66%)	37	9/75 (12.00%)	13	31/145 (21.38%)	55	29/102 (28.43%)	40
Rash maculo-papular † 1	0/87 (0.00%)	0	5/166 (3.01%)	6	4/75 (5.33%)	7	7/145 (4.83%)	7	5/102 (4.90%)	5
Vascular disorders
Flushing † 1	1/87 (1.15%)	2	3/166 (1.81%)	6	2/75 (2.67%)	2	4/145 (2.76%)	5	8/102 (7.84%)	8
Hypertension † 1	3/87 (3.45%)	3	6/166 (3.61%)	12	4/75 (5.33%)	7	8/145 (5.52%)	8	8/102 (7.84%)	9
Lymphoedema † 1	0/87 (0.00%)	0	7/166 (4.22%)	7	5/75 (6.67%)	6	6/145 (4.14%)	6	2/102 (1.96%)	2
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Turner N, Dent RA, O'Shaughnessy J, Kim SB, Isakoff SJ, Barrios C, Saji S, Bondarenko I, Nowecki Z, Lian Q, Reilly SJ, Hinton H, Wongchenko MJ, Kovic B, Mani A, Oliveira M. Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial. Breast Cancer Res Treat. 2022 Feb;191(3):565-576. doi: 10.1007/s10549-021-06450-x. Epub 2021 Dec 3.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03337724
• Other Study ID Numbers: CO40016; 2017-001548-36 ( EudraCT Number )
• First Submitted: November 7, 2017
• First Posted: November 9, 2017
• Results First Submitted: January 2, 2024
• Results First Posted: March 12, 2024
• Last Update Posted: March 12, 2024