A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors (LOTUS)

• ClinicalTrials.gov Identifier: NCT02162719
• Recruitment Status: Completed
• First Posted: June 13, 2014
• Results First Posted: January 11, 2021
• Last Update Posted: March 10, 2021
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Breast Neoplasms
• Interventions: Drug: Ipatasertib; Drug: Paclitaxel; Drug: Placebo
• Enrollment: 124

Participant Flow

Recruitment Details	The study was conducted at 44 centers in 8 countries.
Pre-assignment Details	A total of 166 participants were screened, out of which 42 participants failed screening. A total of 124 participants were enrolled at 44 sites. Results are reported here up to clinical cut-off date of 31st August 2019.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Period Title: Overall Study
Started	62	62
Completed	0	0
Not Completed	62	62
Reason Not Completed
Death	41	46
Lost to Follow-up	1	3
Disease Progression	2	1
Withdrawal by Subject	8	2
Discontinuation of Overall Survival Follow-up	10	10

Baseline Characteristics

Arm/Group Title		Ipatasertib and Paclitaxel	Placebo and Paclitaxel	Total
Arm/Group Description		Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Total of all reporting groups
Overall Number of Baseline Participants		62	62	124
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	62 participants	62 participants	124 participants
		53.6 (13.4)	54.4 (10.9)	54.0 (12.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	62 participants	62 participants	124 participants
	Female	62 100.0%	62 100.0%	124 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	62 participants	62 participants	124 participants
Hispanic or Latino		2	3	5
Not Hispanic or Latino		51	52	103
Not Stated		5	5	10
Unknown		4	2	6
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	62 participants	62 participants	124 participants
Asian		28	30	58
Black or African American		5	3	8
White		26	28	54
Other		3	1	4

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time Frame	Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The Intent to treat (ITT) population was defined as all randomized participants allocated to the treatment arm to which they were randomized.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	62	62
Median (90% Confidence Interval); Unit of Measure: Months
	6.18; (4.57 to 7.33)	4.93; (3.58 to 5.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib and Paclitaxel, Placebo and Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0372
	Comments	Stratification variables were adjuvant/neoadjuvant treatment including treatment with or without radiation, disease-free interval from last dose (<=12 vs >12 months vs. no prior chemotherapy), PTEN status of tumor (H-score 0, vs. 1 to 150, vs. >150).
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (Stratified Analysis)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 90%; 0.40 to 0.91
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
Description	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time Frame	Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants allocated to the treatment arm to which they were randomized. Participants with PTEN-low tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	25	23
Median (90% Confidence Interval); Unit of Measure: Months
	6.18; (3.65 to 9.10)	3.65; (2.53 to 5.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib and Paclitaxel, Placebo and Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1753
	Comments	Stratification variables were adjuvant/neoadjuvant treatment including treatment with or without radiation, disease-free interval from last dose (<=12 vs >12 months vs. no prior chemotherapy), PTEN status of tumor (H-score 0, vs. 1 to 150, vs. >150).
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (Stratified Analysis)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 90%; 0.30 to 1.16
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors
Description	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time Frame	Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized. Participants with PIK3CA/AKT1/PTEN-altered tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	26	16
Median (90% Confidence Interval); Unit of Measure: Months
	9.03; (4.57 to 12.88)	4.93; (3.58 to 5.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib and Paclitaxel, Placebo and Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3636
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (Unstratified Analysis)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 90%; 0.46 to 1.27
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of randomization to the date of death from any cause.
Time Frame	Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	62	62
Median (95% Confidence Interval); Unit of Measure: months
	25.8; (18.6 to 28.6)	16.9; (14.6 to 24.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib and Paclitaxel, Placebo and Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3607
	Comments	Stratification variables were adjuvant/neoadjuvant treatment including treatment with/without radiation, disease-free interval from last dose (<=12 vs >12 months vs. no prior chemotherapy), PTEN status of tumor (H-score 0, vs. 1 to 150, vs. >150).
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (Stratified Analysis)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.28
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	OS in Participants With PTEN-Low Tumors
Description	OS was defined as the time from the date of randomization to the date of death from any cause.
Time Frame	Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized. Participants with PTEN-low tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	25	23
Median (95% Confidence Interval); Unit of Measure: months
	23.1; (18.3 to 28.6)	15.8; (9.0 to 29.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib and Paclitaxel, Placebo and Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4422
	Comments	Stratification variables were adjuvant/neoadjuvant treatment including treatment with/without radiation, disease-free interval from last dose (<=12 vs >12 months vs. no prior chemotherapy), PTEN status of tumor (H-score 0, vs. 1 to 150, vs. >150).
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (Stratified Analysis)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.32 to 1.65
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description	OS was defined as the time from the date of randomization to the date of death from any cause.
Time Frame	Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized. Participants with PIK3CA/AKT1/PTEN-altered tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	26	16
Median (95% Confidence Interval); Unit of Measure: months
	25.8; (18.6 to 35.2)	22.1; (8.7 to 999)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib and Paclitaxel, Placebo and Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7599
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (Unstratified Analysis)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.52 to 2.47
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The Intent to treat (ITT) population was defined as all randomized participants allocated to the treatment arm to which they were randomized.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	62	62
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	40.3; (30.64 to 50.90)	32.3; (23.35 to 42.36)

8. Secondary Outcome

Title	ORR in Participants With PTEN-Low Tumors
Description	Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized. Participants with PTEN-Low Tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	25	23
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	48.0; (30.73 to 64.00)	26.1; (12.02 to 43.12)

9. Secondary Outcome

Title	ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description	Confirmed tumor ORR in subjects with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of subjects who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Subjects for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized. Participants with PIK3CA/AKT1/PTEN-altered tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	26	16
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	50.0; (34.24 to 65.76)	43.8; (23.53 to 66.66)

10. Secondary Outcome

Title	Duration of Response
Description	Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants allocated to the treatment arm to which they were randomized. Only participants who achieved a confirmed objective response were included in the analysis.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	25	20
Median (90% Confidence Interval); Unit of Measure: months
	7.85 [1]; (5.65 to NA)	7.43; (3.88 to 9.20)

[1]

Upper Limit of Duration of Response was not reached due to low number of participants with events.

11. Secondary Outcome

Title	Duration of Response in Participants With PTEN-Low Tumors
Description	Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants allocated to the treatment arm to which they were randomized. Participants with PTEN-low tumors were evaluated for this endpoint. Only participants who achieved a confirmed objective response were included in the analysis.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	12	6
Median (90% Confidence Interval); Unit of Measure: Months
	6.54 [1]; (4.44 to NA)	7.49 [1]; (7.29 to NA)

[1]

Upper Limit of Duration of Response was not reached due to low number of participants with events.

12. Secondary Outcome

Title	Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description	Duration of objective response in participants with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants allocated to the treatment arm to which they were randomized. Participants with PIK3CA/AKT1/PTEN-altered tumors were evaluated for this endpoint. Only participants who achieved a confirmed objective response were included in the analysis.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	13	7
Median (90% Confidence Interval); Unit of Measure: Months
	11.24 [1]; (5.59 to NA)	6.06; (3.78 to 7.56)

[1]

Upper Limit of Duration of Response was not reached due to low number of participants with events.

13. Secondary Outcome

Title	Time to Disease Progression
Description	Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants allocated to the treatment arm to which they were randomized.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	62	62
Median (90% Confidence Interval); Unit of Measure: Months
	6.18; (4.57 to 7.33)	4.96; (3.61 to 5.39)

14. Secondary Outcome

Title	Time to Disease Progression in Participants With PTEN-Low Tumors
Description	Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants allocated to the treatment arm to which they were randomized. Participants with PTEN low tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	25	23
Median (90% Confidence Interval); Unit of Measure: Months
	6.18; (3.65 to 9.10)	3.94; (2.53 to 7.33)

15. Secondary Outcome

Title	Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description	Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time Frame	Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants allocated to the treatment arm to which they were randomized. Participants with PIK3CA/AKT1/PTEN-altered tumors were evaluated for this endpoint.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	26	16
Median (90% Confidence Interval); Unit of Measure: Months
	9.03; (4.57 to 12.88)	4.93; (3.58 to 5.39)

16. Secondary Outcome

Title	Safety: Percentage of Participants With Adverse Events
Description	An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Baseline up to 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first (up to 3 years, 3 months)

Outcome Measure Data

Analysis Population Description

The Safety population included all treated participants with participants allocated to the treatment arm associated with the regimen that they actually received.

Arm/Group Title	Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	61	62
Measure Type: Number; Unit of Measure: Percentage of Participants
	100.0	96.8

17. Secondary Outcome

Title	Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib
Description	PK parameters were not calculated due to sparse PK sampling.
Time Frame	Cycle 1 Day 1, Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

The PK Analysis population was defined as all participants who had evaluable PK data.

Arm/Group Title	Ipatasertib and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	61
Measure Type: Number; Unit of Measure: h*ng/mL/mg
	NA [1]

[1]

Due to sparse PK sampling.

18. Secondary Outcome

Title	Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib
Description	PK parameters were not calculated due to sparse PK sampling.
Time Frame	Cycle 1 Day 1, Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

The PK Analysis population was defined as all participants who had evaluable PK data.

Arm/Group Title	Ipatasertib and Paclitaxel
Arm/Group Description:	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed	61
Measure Type: Number; Unit of Measure: ml/hr
	NA [1]

[1]

Due to sparse PK sampling.

19. Secondary Outcome

Title	Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score
Description	EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1=Not at all to 4=Very much; 2 questions used 7-point scale [1=very poor to 7=Excellent]). Scores averaged, transformed to 0-100 scale; a higher score=better level of functioning. For symptom scale scores, higher level=severe level of symptoms. "A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). PRO measures were analyzed from baseline up to cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).
Time Frame	Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1

Outcome Measure Data

Analysis Population Description

The PRO Analysis population was defined as the ITT population with a baseline and at least one post baseline PRO assessment. Data presented below is only for participants included in the actual analysis.

Arm/Group Title		Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:		Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed		57	53
Mean (Standard Deviation); Unit of Measure: unit on a scale
Appetite loss:Cycle 2	Number Analyzed	57 participants	53 participants
		7.60 (28.18)	-0.63 (24.88)
Appetite loss:Cycle 3	Number Analyzed	46 participants	43 participants
		9.42 (21.84)	-3.88 (24.35)
Appetite loss:Cycle 4	Number Analyzed	49 participants	40 participants
		5.44 (23.91)	-4.17 (25.25)
Appetite loss:Cycle 5	Number Analyzed	35 participants	30 participants
		0.00 (18.08)	-1.11 (25.50)
Cognitive Functioning: Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		1.17 (14.04)	0.63 (17.28)
Cognitive Functioning: Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		-1.81 (19.64)	-1.81 (19.64)
Cognitive Functioning: Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		-3.40 (15.95)	0.00 (20.32)
Cognitive Functioning: Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		0.00 (13.80)	-4.44 (19.54)
Constipation: Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		5.85 (24.50)	0.63 (25.73)
Constipation: Cycle 3 Day 1	Number Analyzed	46 participants	42 participants
		2.90 (19.66)	1.59 (22.03)
Constipation: Cycle 4 Day 1	Number Analyzed	48 participants	40 participants
		1.39 (16.78)	0.83 (30.65)
Constipation: Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		2.78 (14.64)	1.11 (20.50)
Diarrhoea: Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		17.54 (30.28)	1.89 (15.21)
Diarrhoea: Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		23.91 (34.90)	3.88 (18.13)
Diarrhoea: Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		19.73 (34.64)	0.83 (15.99)
Diarrhoea: Cycle 5 Day 1	Number Analyzed	35 participants	30 participants
		21.90 (37.87)	1.11 (16.34)
Dyspnea: Cycle 2 Day 1	Number Analyzed	57 participants	52 participants
		2.92 (19.19)	0.00 (18.67)
Dyspnea: Cycle 3 Day 1	Number Analyzed	46 participants	41 participants
		5.07 (23.27)	2.44 (22.84)
Dyspnea: Cycle 4 Day 1	Number Analyzed	49 participants	39 participants
		3.40 (25.68)	5.13 (22.35)
Dyspnea: Cycle 5 Day 1	Number Analyzed	36 participants	28 participants
		5.56 (25.82)	4.76 (23.51)
Emotional Functioning: Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		12.09 (15.90)	4.72 (16.87)
Emotional Functioning: Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		7.37 (17.18)	3.88 (20.36)
Emotional Functioning: Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		8.22 (16.53)	2.71 (21.47)
Emotional Functioning: Cycle 5 Day 1	Number Analyzed	35 participants	30 participants
		8.73 (16.30)	1.39 (17.79)
Fatigue: Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		7.99 (22.69)	-1.36 (16.98)
Fatigue: Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		9.18 (22.63)	1.42 (19.44)
Fatigue: Cycle 4 Day 1	Number Analyzed	49 participants	39 participants
		7.94 (20.91)	1.85 (21.64)
Fatigue: Cycle 5 Day 1	Number Analyzed	35 participants	30 participants
		10.32 (20.35)	1.67 (20.59)
Financial difficulties Cycle 2 Day 1	Number Analyzed	56 participants	52 participants
		3.57 (21.72)	0.00 (20.87)
Financial difficulties Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		0.72 (22.76)	-3.88 (24.35)
Financial difficulties Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		3.40 (23.81)	-0.83 (29.71)
Financial difficulties Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		2.78 (25.67)	1.11 (26.96)
Nausea/Vomiting Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		9.06 (19.43)	2.83 (15.24)
Nausea/Vomiting Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		6.52 (14.26)	3.10 (14.21)
Nausea/Vomiting Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		6.80 (17.32)	3.75 (17.50)
Nausea/Vomiting Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		3.70 (7.03)	0.00 (23.16)
Pain Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		-3.80 (22.93)	-7.86 (23.02)
Pain Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		-4.71 (26.45)	-7.36 (26.80)
Pain Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		1.36 (28.63)	-3.33 (31.62)
Pain Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		0.00 (26.13)	-5.56 (25.27)
Physical Functioning Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		-4.53 (14.23)	-0.16 (12.96)
Physical Functioning Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		-5.94 (15.54)	-1.71 (13.88)
Physical Functioning Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		-9.12 (13.92)	-3.17 (16.54)
Physical Functioning Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		-8.56 (13.47)	-4.44 (14.26)
Global health status Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		-4.68 (22.33)	4.72 (18.38)
Global health status Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		-8.15 (21.55)	3.29 (21.37)
Global health status Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		-8.50 (21.62)	-1.46 (26.61)
Global health status Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		-6.48 (22.55)	-5.00 (21.62)
Role Functioning Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		-5.85 (20.04)	0.63 (22.40)
Role Functioning Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		-10.51 (24.43)	-2.71 (22.69)
Role Functioning Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		-13.95 (25.76)	-6.25 (26.34)
Role Functioning Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		-11.57 (21.76)	-7.22 (21.30)
Social Functioning Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		-2.05 (26.92)	0.00 (23.34)
Social Functioning Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		-2.17 (23.99)	-3.49 (26.11)
Social Functioning Cycle 4 Day 1	Number Analyzed	49 participants	40 participants
		-7.14 (27.00)	-5.83 (23.74)
Social Functioning Cycle 5 Day 1	Number Analyzed	35 participants	30 participants
		-4.76 (31.72)	-9.44 (24.24)
Insomnia Cycle 2 Day 1	Number Analyzed	57 participants	53 participants
		2.92 (31.67)	-5.03 (24.80)
Insomnia Cycle 3 Day 1	Number Analyzed	46 participants	43 participants
		2.90 (25.17)	-3.10 (25.00)
Insomnia Cycle 4 Day 1	Number Analyzed	46 participants	43 participants
		7.48 (28.27)	5.83 (31.02)
Insomnia Cycle 5 Day 1	Number Analyzed	36 participants	30 participants
		1.85 (34.68)	-5.56 (29.14)

20. Secondary Outcome

Title	PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30
Description	Subjects reporting >/= 10-point increase compared to baseline (Cycle 1 Day 1) were considered "improved", those reporting <10-point difference were considered "remained stable", and those reporting >/=10-point decrease were considered "worsened". A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). Patient reported outcome measures were analyzed from baseline up to and including cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).
Time Frame	Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1

Outcome Measure Data

Analysis Population Description

The PRO Analysis population was defined as the ITT population with a baseline and at least one post baseline PRO assessment. Data presented below is only for participants included in the actual analysis.

Arm/Group Title		Ipatasertib and Paclitaxel	Placebo and Paclitaxel
Arm/Group Description:		Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Overall Number of Participants Analyzed		57	53
Measure Type: Number; Unit of Measure: Percentage of Participants
Improved Appetite Loss: Cycle 2	Number Analyzed	57 participants	53 participants
		10.5	18.9
Maintained Appetite Loss: Cycle 2	Number Analyzed	57 participants	53 participants
		64.9	66.0
Worsened Appetite Loss: Cycle 2	Number Analyzed	57 participants	53 participants
		24.6	15.1
Improved Appetite Loss: Cycle 3	Number Analyzed	46 participants	43 participants
		8.7	27.9
Maintained Appetite Loss: Cycle 3	Number Analyzed	46 participants	43 participants
		56.5	53.5
Worsened Appetite Loss: Cycle 3	Number Analyzed	46 participants	43 participants
		34.8	18.6
Improved Appetite Loss: Cycle 4	Number Analyzed	49 participants	40 participants
		10.2	30.0
Maintained Appetite Loss: Cycle 4	Number Analyzed	49 participants	40 participants
		65.3	57.5
Worsened Appetite Loss: Cycle 4	Number Analyzed	49 participants	40 participants
		24.5	12.5
Improved Appetite Loss: Cycle 5	Number Analyzed	35 participants	30 participants
		8.6	26.7
Maintained Appetite Loss: Cycle 5	Number Analyzed	35 participants	30 participants
		80.0	53.3
Worsened Appetite Loss: Cycle 5	Number Analyzed	35 participants	30 participants
		11.4	20.0
Improved Diarrhea: Cycle 2	Number Analyzed	57 participants	53 participants
		3.5	7.5
Maintained Diarrhea: Cycle 2	Number Analyzed	57 participants	53 participants
		50.9	79.2
Worsened Diarrhea: Cycle 2	Number Analyzed	57 participants	53 participants
		45.6	13.2
Improved Diarrhea: Cycle 3	Number Analyzed	46 participants	43 participants
		8.7	9.3
Maintained Diarrhea: Cycle 3	Number Analyzed	46 participants	43 participants
		39.1	69.8
Worsened Diarrhea: Cycle 3	Number Analyzed	46 participants	43 participants
		52.2	20.9
Improved Diarrhea: Cycle 4	Number Analyzed	49 participants	40 participants
		10.2	10.0
Maintained Diarrhea: Cycle 4	Number Analyzed	49 participants	40 participants
		38.8	77.5
Worsened Diarrhea: Cycle 4	Number Analyzed	49 participants	40 participants
		51.0	12.5
Improved Diarrhea: Cycle 5	Number Analyzed	35 participants	30 participants
		14.3	10.0
Maintained Diarrhea: Cycle 5	Number Analyzed	35 participants	30 participants
		34.3	76.7
Worsened Diarrhea: Cycle 5	Number Analyzed	35 participants	30 participants
		51.4	13.3
Improved Fatigue: Cycle 2	Number Analyzed	57 participants	53 participants
		21.1	34.0
Maintained Fatigue: Cycle 2	Number Analyzed	57 participants	53 participants
		29.85	30.2
Worsened Fatigue: Cycle 2	Number Analyzed	57 participants	53 participants
		49.1	35.8
Improved Fatigue: Cycle 3	Number Analyzed	46 participants	43 participants
		23.9	34.9
Maintained Fatigue: Cycle 3	Number Analyzed	57 participants	53 participants
		15.2	30.2
Worsened Fatigue: Cycle 3	Number Analyzed	57 participants	53 participants
		60.9	34.9
Improved Fatigue: Cycle 4	Number Analyzed	46 participants	43 participants
		24.5	28.2
Maintained Fatigue: Cycle 4	Number Analyzed	46 participants	43 participants
		28.6	28.2
Worsened Fatigue: Cycle 4	Number Analyzed	46 participants	43 participants
		46.9	43.6
Improved Fatigue: Cycle 5	Number Analyzed	46 participants	43 participants
		20.0	30.0
Maintained Fatigue: Cycle 5	Number Analyzed	46 participants	43 participants
		20.0	43.3
Worsened Fatigue: Cycle 5	Number Analyzed	46 participants	43 participants
		60.0	26.7
Improved Nausea/Vomiting Cycle 2	Number Analyzed	57 participants	53 participants
		3.5	11.3
Maintained Nausea/Vomiting Cycle 2	Number Analyzed	57 participants	53 participants
		61.4	64.2
Worsened Nausea/Vomiting Cycle 2	Number Analyzed	57 participants	53 participants
		35.1	24.5
Improved Nausea/Vomiting Cycle 3	Number Analyzed	46 participants	43 participants
		4.3	9.3
Maintained Nausea/Vomiting Cycle 3	Number Analyzed	46 participants	43 participants
		65.2	62.8
Worsened Nausea/Vomiting Cycle 3	Number Analyzed	46 participants	43 participants
		30.4	27.9
Improved Nausea/Vomiting Cycle 4	Number Analyzed	49 participants	39 participants
		2.0	7.5
Maintained Nausea/Vomiting Cycle 4	Number Analyzed	49 participants	39 participants
		73.5	67.5
Worsened Nausea/Vomiting Cycle 4	Number Analyzed	49 participants	39 participants
		24.5	25.0
Improved Nausea/Vomiting Cycle 5	Number Analyzed	36 participants	30 participants
		0	16.7
Maintained Nausea/Vomiting Cycle 5	Number Analyzed	36 participants	30 participants
		77.8	60.0
Worsened Nausea/Vomiting Cycle 5	Number Analyzed	36 participants	30 participants
		22.2	23.3
Improved Cognitive Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		22.8	17.0
Maintained Cognitive Function Cycle 2	Number Analyzed	57 participants	53 participants
		61.4	60.4
Worsened Cognitive Function Cycle 2	Number Analyzed	57 participants	53 participants
		15.8	22.6
Improved Cognitive Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		26.1	16.3
Maintained Cognitive Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		47.8	53.5
Worsened Cognitive Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		26.1	30.2
Improved Cognitive Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		20.4	22.5
Maintained Cognitive Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		51.0	52.5
Worsened Cognitive Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		28.6	25.0
Improved Cognitive Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		19.4	20.0
Maintained Cognitive Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		58.3	46.7
Worsened Cognitive Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		22.2	33.3
Improved Constipation Cycle 2	Number Analyzed	57 participants	53 participants
		8.8	17.0
Maintained Constipation Cycle 2	Number Analyzed	57 participants	53 participants
		73.7	64.2
Worsened Constipation Cycle 2	Number Analyzed	57 participants	53 participants
		17.5	18.9
Improved Constipation Cycle 3	Number Analyzed	46 participants	42 participants
		10.9	9.5
Maintained Constipation Cycle 3	Number Analyzed	46 participants	42 participants
		71.7	71.4
Worsened Constipation Cycle 3	Number Analyzed	46 participants	42 participants
		17.4	19.0
Improved Constipation Cycle 4	Number Analyzed	48 participants	40 participants
		10.4	15.0
Maintained Constipation Cycle 4	Number Analyzed	48 participants	40 participants
		75.0	60.0
Worsened Constipation Cycle 4	Number Analyzed	48 participants	40 participants
		14.6	25.0
Improved Constipation Cycle 5	Number Analyzed	36 participants	30 participants
		5.6	13.3
Maintained Constipation Cycle 5	Number Analyzed	36 participants	30 participants
		80.6	73.3
Worsened Constipation Cycle 5	Number Analyzed	36 participants	30 participants
		13.9	13.3
Improved Dyspnea Cycle 2	Number Analyzed	57 participants	52 participants
		5.3	15.4
Maintained Dyspnea Cycle 2	Number Analyzed	57 participants	52 participants
		77.2	69.2
Worsened Dyspnea Cycle 2	Number Analyzed	57 participants	52 participants
		17.5	15.4
Improved Dyspnea Cycle 3	Number Analyzed	46 participants	41 participants
		6.5	14.6
Maintained Dyspnea Cycle 3	Number Analyzed	46 participants	41 participants
		67.4	68.3
Worsened Dyspnea Cycle 3	Number Analyzed	46 participants	41 participants
		26.1	17.1
Improved Dyspnea Cycle 4	Number Analyzed	49 participants	39 participants
		10.2	12.8
Maintained Dyspnea Cycle 4	Number Analyzed	49 participants	39 participants
		69.4	61.5
Worsened Dyspnea Cycle 4	Number Analyzed	49 participants	39 participants
		20.4	25.6
Improved Dyspnea Cycle 5	Number Analyzed	36 participants	28 participants
		8.3	14.3
Maintained Dyspnea Cycle 5	Number Analyzed	36 participants	28 participants
		69.4	60.7
Worsened Dyspnea Cycle 5	Number Analyzed	36 participants	28 participants
		22.2	25.0
Improved Emotional Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		50.9	35.8
Maintained Emotional Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		43.9	50.9
Worsened Emotional Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		5.3	13.2
Improved Emotional Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		45.7	37.2
Maintained Emotional Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		45.7	41.9
Worsened Emotional Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		8.7	20.9
Improved Emotional Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		42.9	30.0
Maintained Emotional Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		49.0	45.0
Worsened Emotional Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		8.2	25.0
Improved Emotional Functioning Cycle 5	Number Analyzed	35 participants	30 participants
		42.9	36.7
Maintained Emotional Functioning Cycle 5	Number Analyzed	35 participants	30 participants
		48.6	36.7
Worsened Emotional Functioning Cycle 5	Number Analyzed	35 participants	30 participants
		8.6	26.7
Improved Financial Difficulties Cycle 2	Number Analyzed	56 participants	52 participants
		10.7	13.5
Maintained Financial Difficulties Cycle 2	Number Analyzed	56 participants	52 participants
		73.2	73.1
Worsened Financial Difficulties Cycle 2	Number Analyzed	56 participants	52 participants
		16.1	13.5
Improved Financial Difficulties Cycle 3	Number Analyzed	46 participants	43 participants
		13.0	18.6
Maintained Financial Difficulties Cycle 3	Number Analyzed	46 participants	43 participants
		73.9	72.1
Worsened Financial Difficulties Cycle 3	Number Analyzed	46 participants	43 participants
		13.0	9.3
Improved Financial Difficulties Cycle 4	Number Analyzed	49 participants	40 participants
		10.2	17.5
Maintained Financial Difficulties Cycle 4	Number Analyzed	49 participants	40 participants
		73.5	70.0
Worsened Financial Difficulties Cycle 4	Number Analyzed	49 participants	40 participants
		16.3	12.5
Improved Financial Difficulties Cycle 5	Number Analyzed	36 participants	30 participants
		13.9	20.0
Maintained Financial Difficulties Cycle 5	Number Analyzed	36 participants	30 participants
		66.7	63.3
Worsened Financial Difficulties Cycle 5	Number Analyzed	36 participants	30 participants
		19.4	16.7
Improved Pain Cycle 2	Number Analyzed	57 participants	53 participants
		35.1	35.8
Maintained Pain Cycle 2	Number Analyzed	57 participants	53 participants
		40.4	45.3
Worsened Pain Cycle 2	Number Analyzed	57 participants	53 participants
		24.6	18.9
Improved Pain Cycle 3	Number Analyzed	46 participants	43 participants
		37.0	39.5
Maintained Pain Cycle 3	Number Analyzed	46 participants	43 participants
		39.1	39.5
Worsened Pain Cycle	Number Analyzed	46 participants	43 participants
		23.9	20.9
Improved Pain Cycle 4	Number Analyzed	49 participants	40 participants
		32.7	37.5
Maintained Pain Cycle 4	Number Analyzed	49 participants	40 participants
		32.7	35.0
Worsened Pain Cycle 4	Number Analyzed	49 participants	40 participants
		34.7	27.5
Improved Pain Cycle 5	Number Analyzed	36 participants	30 participants
		33.3	33.3
Maintained Pain Cycle 5	Number Analyzed	36 participants	30 participants
		30.6	40.0
Worsened Pain Cycle 5	Number Analyzed	36 participants	30 participants
		36.1	26.7
Improved Physical Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		7.0	13.2
Maintained Physical Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		68.4	75.5
Worsened Physical Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		24.6	11.3
Improved Physical Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		8.7	16.3
Maintained Physical Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		67.4	60.5
Worsened Physical Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		23.9	23.3
Improved Physical Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		4.1	17.5
Maintained Physical Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		55.1	57.5
Worsened Physical Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		40.8	25.0
Improved Physical Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		8.3	16.7
Maintained Physical Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		44.4	46.7
Worsened Physical Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		47.2	36.7
Improved Global Health Status/QoL Cycle 2	Number Analyzed	57 participants	53 participants
		19.3	26.4
Maintained Global Health Status/QoL Cycle 2	Number Analyzed	57 participants	53 participants
		45.6	58.5
Worsened Global Health Status/QoL Cycle 2	Number Analyzed	57 participants	53 participants
		35.1	15.1
Improved Global Health Status/QoL Cycle 3	Number Analyzed	46 participants	43 participants
		17.4	25.6
Maintained Global Health Status/QoL Cycle 3	Number Analyzed	46 participants	43 participants
		37.0	60.5
Worsened Global Health Status/QoL Cycle 3	Number Analyzed	46 participants	43 participants
		45.7	14.0
Improved Global Health Status/QoL Cycle 4	Number Analyzed	49 participants	40 participants
		14.3	25.0
Maintained Global Health Status/QoL Cycle 4	Number Analyzed	49 participants	40 participants
		51.0	42.5
Worsened Global Health Status/QoL Cycle 4	Number Analyzed	49 participants	40 participants
		34.7	32.5
Improved Global Health Status/QoL Cycle 5	Number Analyzed	36 participants	30 participants
		11.1	20.0
Maintained Global Health Status/QoL Cycle 5	Number Analyzed	36 participants	30 participants
		58.3	46.7
Worsened Global Health Status/QoL Cycle 5	Number Analyzed	36 participants	30 participants
		30.6	33.3
Improved Role Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		17.5	24.5
Maintained Role Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		52.6	45.3
Worsened Role Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		29.8	30.2
Improved Role Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		13.0	27.9
Maintained Role Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		47.8	46.5
Worsened Role Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		39.1	25.6
Improved Role Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		12.2	25.0
Maintained Role Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		38.8	37.5
Worsened Role Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		49.0	37.5
Improved Role Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		11.1	16.7
Maintained Role Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		47.2	40.0
Worsened Role Functioning Cycle 5	Number Analyzed	36 participants	30 participants
		41.7	43.3
Improved Social Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		21.1	22.6
Maintained Social Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		49.1	49.1
Worsened Social Functioning Cycle 2	Number Analyzed	57 participants	53 participants
		29.8	28.3
Improved Social Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		17.4	16.3
Maintained Social Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		52.2	53.5
Worsened Social Functioning Cycle 3	Number Analyzed	46 participants	43 participants
		30.4	30.2
Improved Social Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		16.3	10.0
Maintained Social Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		49.0	47.5
Worsened Social Functioning Cycle 4	Number Analyzed	49 participants	40 participants
		34.7	42.5
Improved Social Functioning Cycle 5	Number Analyzed	35 participants	30 participants
		17.1	13.3
Maintained Social Functioning Cycle 5	Number Analyzed	35 participants	30 participants
		48.6	36.7
Worsened Social Functioning Cycle 5	Number Analyzed	35 participants	30 participants
		34.3	50.0

Adverse Events

Time Frame	Baseline up to 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first (up to 3 years, 3 months)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ipatasertib and Paclitaxel		Placebo and Paclitaxel
Arm/Group Description	Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.		Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
All-Cause Mortality
	Ipatasertib and Paclitaxel		Placebo and Paclitaxel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	41/61 (67.21%)		46/62 (74.19%)
Serious Adverse Events
	Ipatasertib and Paclitaxel		Placebo and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/61 (29.51%)		12/62 (19.35%)
Blood and lymphatic system disorders
Pancytopenia † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Febrile Neutropenia † 1	2/61 (3.28%)	2	0/62 (0.00%)	0
Gastrointestinal disorders
Constipation † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Diarrhoea † 1	3/61 (4.92%)	3	0/62 (0.00%)	0
Nausea † 1	1/61 (1.64%)	2	0/62 (0.00%)	0
Pancreatitis † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
General disorders
Death † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Pyrexia † 1	2/61 (3.28%)	3	1/62 (1.61%)	1
Hepatobiliary disorders
Cholestasis † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Infections and infestations
Atypical Pneumonia † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Cystitis † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Gastroenteritis † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Influenza † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Pneumonia † 1	3/61 (4.92%)	3	0/62 (0.00%)	0
Retroperitoneal Infection † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Tuberculosis † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Upper Respiratory Tract Infection † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Wound Infection † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Vascular device infection † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Investigations
Neutrophil Count Decreased † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Metabolism and nutrition disorders
Cell Death † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Decreased Appetite † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Hyponatraemia † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Musculoskeletal and connective tissue disorders
Bone Pain † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Muscular weakness † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Triple negative breast cancer † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Nervous system disorders
Spinal Cord Compression † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Psychiatric disorders
Depression † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	0/61 (0.00%)	0	1/62 (1.61%)	2
Pleural effusion † 1	0/61 (0.00%)	0	1/62 (1.61%)	1
Vascular disorders
Embolism † 1	1/61 (1.64%)	1	0/62 (0.00%)	0
1 Term from vocabulary, MedDRA 22.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ipatasertib and Paclitaxel		Placebo and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/61 (100.00%)		59/62 (95.16%)
Blood and lymphatic system disorders
Anaemia † 1	9/61 (14.75%)	17	8/62 (12.90%)	11
Leukopenia † 1	2/61 (3.28%)	3	4/62 (6.45%)	6
Neutropenia † 1	13/61 (21.31%)	38	15/62 (24.19%)	36
Eye disorders
Dry Eye † 1	4/61 (6.56%)	5	3/62 (4.84%)	3
Gastrointestinal disorders
Abdominal Pain † 1	9/61 (14.75%)	13	7/62 (11.29%)	9
Abdominal Pain Upper † 1	4/61 (6.56%)	4	4/62 (6.45%)	5
Constipation † 1	12/61 (19.67%)	17	9/62 (14.52%)	11
Diarrhoea † 1	56/61 (91.80%)	205	13/62 (20.97%)	19
Dry Mouth † 1	2/61 (3.28%)	3	5/62 (8.06%)	5
Dyspepsia † 1	8/61 (13.11%)	11	6/62 (9.68%)	6
Flatulence † 1	4/61 (6.56%)	4	2/62 (3.23%)	2
Gastritis † 1	4/61 (6.56%)	5	0/62 (0.00%)	0
Nausea † 1	32/61 (52.46%)	67	21/62 (33.87%)	28
Stomatitis † 1	11/61 (18.03%)	14	5/62 (8.06%)	6
Vomiting † 1	17/61 (27.87%)	39	14/62 (22.58%)	15
General disorders
Asthenia † 1	17/61 (27.87%)	41	7/62 (11.29%)	7
Chest Discomfort † 1	4/61 (6.56%)	4	1/62 (1.61%)	1
Chest Pain † 1	4/61 (6.56%)	5	6/62 (9.68%)	6
Fatigue † 1	18/61 (29.51%)	26	20/62 (32.26%)	32
Mucosal Inflammation † 1	4/61 (6.56%)	7	4/62 (6.45%)	5
Oedema Peripheral † 1	7/61 (11.48%)	9	5/62 (8.06%)	6
Pyrexia † 1	11/61 (18.03%)	13	7/62 (11.29%)	9
Infections and infestations
Nasopharyngitis † 1	8/61 (13.11%)	12	5/62 (8.06%)	6
Upper Respiratory Tract Infection † 1	10/61 (16.39%)	15	4/62 (6.45%)	10
Urinary Tract Infection † 1	5/61 (8.20%)	6	4/62 (6.45%)	4
Influenza † 1	4/61 (6.56%)	6	1/62 (1.61%)	1
Rhinitis † 1	4/61 (6.56%)	5	1/62 (1.61%)	1
Investigations
Alanine Aminotransferase Increased † 1	3/61 (4.92%)	5	4/62 (6.45%)	4
Aspartate Aminotransferase Increased † 1	5/61 (8.20%)	8	3/62 (4.84%)	6
Neutrophil Count Decreased † 1	8/61 (13.11%)	19	9/62 (14.52%)	20
Metabolism and nutrition disorders
Decreased appetite † 1	12/61 (19.67%)	15	11/62 (17.74%)	15
Hypercholesterolaemia † 1	6/61 (9.84%)	6	1/62 (1.61%)	2
Hyperglycaemia † 1	5/61 (8.20%)	10	2/62 (3.23%)	3
Hypokalaemia † 1	4/61 (6.56%)	7	2/62 (3.23%)	2
Musculoskeletal and connective tissue disorders
Arthralgia † 1	12/61 (19.67%)	16	5/62 (8.06%)	5
Back Pain † 1	7/61 (11.48%)	10	6/62 (9.68%)	7
Musculoskeletal Chest Pain † 1	4/61 (6.56%)	9	4/62 (6.45%)	4
Musculoskeletal Pain † 1	3/61 (4.92%)	4	4/62 (6.45%)	4
Myalgia † 1	17/61 (27.87%)	42	15/62 (24.19%)	25
Pain in Extremity † 1	5/61 (8.20%)	8	2/62 (3.23%)	2
Bone pain † 1	4/61 (6.56%)	6	1/62 (1.61%)	1
Nervous system disorders
Dizziness † 1	11/61 (18.03%)	19	9/62 (14.52%)	10
Dysgeusia † 1	4/61 (6.56%)	4	5/62 (8.06%)	5
Headache † 1	11/61 (18.03%)	15	13/62 (20.97%)	14
Hypoaesthesia † 1	4/61 (6.56%)	6	0/62 (0.00%)	0
Neuropathy Peripheral † 1	12/61 (19.67%)	17	14/62 (22.58%)	18
Paraesthesia † 1	6/61 (9.84%)	10	7/62 (11.29%)	10
Peripheral Sensory Neuropathy † 1	16/61 (26.23%)	33	10/62 (16.13%)	16
Psychiatric disorders
Anxiety † 1	2/61 (3.28%)	3	4/62 (6.45%)	6
Insomnia † 1	13/61 (21.31%)	19	8/62 (12.90%)	9
Depression † 1	4/61 (6.56%)	4	2/62 (3.23%)	2
Respiratory, thoracic and mediastinal disorders
Cough † 1	9/61 (14.75%)	11	8/62 (12.90%)	12
Epistaxis † 1	7/61 (11.48%)	8	2/62 (3.23%)	2
Dyspnoea † 1	9/61 (14.75%)	13	5/62 (8.06%)	6
Productive cough † 1	4/61 (6.56%)	4	2/62 (3.23%)	2
Skin and subcutaneous tissue disorders
Alopecia † 1	33/61 (54.10%)	37	29/62 (46.77%)	34
Dermatitis Acneiform † 1	10/61 (16.39%)	17	5/62 (8.06%)	5
Nail Disorder † 1	4/61 (6.56%)	7	4/62 (6.45%)	4
Onycholysis † 1	4/61 (6.56%)	4	1/62 (1.61%)	1
Pruritus † 1	9/61 (14.75%)	14	5/62 (8.06%)	5
Rash † 1	17/61 (27.87%)	28	13/62 (20.97%)	17
Rash Maculo-Papular † 1	1/61 (1.64%)	1	4/62 (6.45%)	7
Vascular disorders
Flushing † 1	4/61 (6.56%)	4	3/62 (4.84%)	3
Hot Flush † 1	5/61 (8.20%)	5	3/62 (4.84%)	3
Hypertension † 1	3/61 (4.92%)	3	4/62 (6.45%)	4
1 Term from vocabulary, MedDRA 22.1; † 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):

Kim SB, Dent R, Im SA, Espie M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1360-1372. doi: 10.1016/S1470-2045(17)30450-3. Epub 2017 Aug 8. Erratum In: Lancet Oncol. 2018 Dec;19(12):e667.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT02162719
• Other Study ID Numbers: GO29227; 2014-000469-35 ( EudraCT Number )
• First Submitted: June 11, 2014
• First Posted: June 13, 2014
• Results First Submitted: December 15, 2020
• Results First Posted: January 11, 2021
• Last Update Posted: March 10, 2021