Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43871 clinical trials with a EudraCT protocol, of which 7290 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
A Phase III, Double-blind, Placebo-controlled, Randomized Study of Ipatasertib in Combination with Atezolizumab and Paclitaxel as a Treatment for Patients with Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer

Summary
EudraCT number	2019-000810-12
Trial protocol	CZ FR AT PL PT IE ES FI HU BE GR BG DK RO IT
Global end of trial date	28 Feb 2023

Results information
Results version number	v1(current)
This version publication date	13 Mar 2024
First version publication date	13 Mar 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CO41101

ISRCTN number

-

US NCT number

NCT04177108

WHO universal trial number (UTN)

-

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, 4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, CH +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, CH +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

28 Feb 2023

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

28 Feb 2023

Was the trial ended prematurely?

Yes

Main objective of the trial

The main purpose of this study is to evaluate the efficacy and safety of ipatasertib in combination with atezolizumab and paclitaxel in locally advanced or metastatic Triple-Negative Breast Cancer (TNBC) previously untreated in this setting.

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

25 Nov 2019

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 13

Country: Number of subjects enrolled

Australia: 18

Country: Number of subjects enrolled

Austria: 1

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

Bulgaria: 1

Country: Number of subjects enrolled

Brazil: 2

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Switzerland: 1

Country: Number of subjects enrolled

Colombia: 3

Country: Number of subjects enrolled

Costa Rica: 3

Country: Number of subjects enrolled

Czechia: 2

Country: Number of subjects enrolled

Denmark: 2

Country: Number of subjects enrolled

Spain: 27

Country: Number of subjects enrolled

Finland: 2

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

Hong Kong: 5

Country: Number of subjects enrolled

India: 1

Country: Number of subjects enrolled

Israel: 1

Country: Number of subjects enrolled

Italy: 18

Country: Number of subjects enrolled

Japan: 6

Country: Number of subjects enrolled

Korea, Republic of: 28

Country: Number of subjects enrolled

Mexico: 16

Country: Number of subjects enrolled

Peru: 12

Country: Number of subjects enrolled

Poland: 12

Country: Number of subjects enrolled

Portugal: 2

Country: Number of subjects enrolled

Romania: 2

Country: Number of subjects enrolled

Russian Federation: 8

Country: Number of subjects enrolled

Thailand: 10

Country: Number of subjects enrolled

Türkiye: 9

Country: Number of subjects enrolled

Taiwan: 9

Country: Number of subjects enrolled

Ukraine: 13

Country: Number of subjects enrolled

United States: 8

Worldwide total number of subjects

242

EEA total number of subjects

71

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

201

From 65 to 84 years

41

85 years and over

0

Subject disposition

Top of page

Recruitment details

Participants took part in the study at 215 investigative centers from 25 November 2019 to 28 February 2023.

Screening details

A total of 242 participants with Advanced TNBC were enrolled, of which 127 participants were randomised to cohort 1 {programmed death-ligand 1 (PD-L1) Non-positive} and 115 participants to cohort 2 (PD-L1 positive).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Are arms mutually exclusive

Yes

Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Arm description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

Ipatasertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ipatasertib will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Paclitaxel will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.

Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel

Arm description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

Ipatasertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ipatasertib will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Atezolizumab_matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab matching placebo will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Paclitaxel will be administered as per the dosage regimen mentioned in arm descriptions.

Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Arm description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

Ipatasertib_matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ipatasertib matching placebo will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Atezolizumab_matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab matching placebo will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Paclitaxel will be administered as per the dosage regimen mentioned in arm descriptions.

Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Arm description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

Ipatasertib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ipatasertib will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Paclitaxel will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.

Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel

Arm description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

Ipatasertib_matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ipatasertib matching placebo will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Paclitaxel will be administered as per the dosage regimen mentioned in arm descriptions.

Number of subjects in period 1	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel
Started	43	43	41	58	57
Completed	0	0	0	0	0
Not completed	43	43	41	58	57
Adverse event, serious fatal	16	19	13	17	18
Physician decision	23	15	18	29	23
Consent withdrawn by subject	4	8	9	11	13
Reason Not Specified	-	1	-	-	2
Lost to follow-up	-	-	1	1	1

Baseline characteristics

Top of page

Reporting group title

Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group values	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel	Total
Number of subjects	43	43	41	58	57	242
Age categorical
Units: participants
Age Continuous
Units: years
arithmetic mean (standard deviation)	55.5 ( 11.7 )	50.8 ( 11.6 )	53.5 ( 10.7 )	53.7 ( 12.1 )	51.1 ( 11.7 )	-
Sex/Gender, Customized
Units: participants
Female	43	43	41	58	57	242
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	5	3	1	5	6	20
Asian	10	7	9	19	16	61
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	2	2	0	2	2	8
White	26	29	29	29	32	145
More than one race	0	0	1	0	1	2
Unknown or Not Reported	0	2	1	3	0	6
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	8	9	6	15	14	52
Not Hispanic or Latino	32	32	35	41	43	183
Unknown or Not Reported	3	2	0	2	0	7

End points

Top of page

Reporting group title

Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Primary: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Top of page

End point title

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

End point description

PFS was defined as the time from randomization to the first occurrence of disease progression as determined locally by RECIST or death from any cause during treatment, whichever occurs first. Intent-to-Treat (ITT) population included all participants randomised in this study.

End point type

Primary

End point timeframe

From Randomisation to disease progression, study completion, or death (up to 39 months)

End point values	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel
Number of subjects analysed	43	43	41	58	57
Units: months
median (confidence interval 95%)	7.1 (5.1 to 9.3)	5.6 (3.7 to 8.2)	3.7 (3.6 to 5.4)	5.6 (5.4 to 9.2)	5.7 (4.0 to 9.1)

Cohort 1 Arm A Versus Cohort 1 Arm C

Comparison groups

Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel v Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Number of subjects included in analysis

84

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0098

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

0.85

Cohort 2 Arm A Versus Cohort 2 Arm B

Comparison groups

Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel v Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9809

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.58

Cohort 1 Arm B Versus Cohort 1 Arm C

Comparison groups

Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel v Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Number of subjects included in analysis

84

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2396

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.25

Primary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

OS was defined as the time from randomisation to the time of death from any cause on study. Here, 99999 indicates that median and upper limit of 95% confidence interval (CI) could not be calculated due to insufficient number of participants with events. ITT population included all participants randomised in this study.

End point type

Primary

End point timeframe

From randomization up to study completion or death (Up to 39 months)

End point values	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel
Number of subjects analysed	43	43	41	58	57
Units: months
median (confidence interval 95%)	15.7 (12.5 to 99999)	15.3 (15.3 to 99999)	16.6 (9.6 to 99999)	99999 (14.1 to 99999)	17.2 (13.4 to 99999)

Cohort 1 Arm A Versus Cohort 1 Arm C

Comparison groups

Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel v Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Number of subjects included in analysis

84

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6805

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

2.51

Cohort 2 Arm A Versus Cohort 2 Arm B

Comparison groups

Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel v Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9164

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

2.06

Cohort 1 Arm B Versus Cohort 1 Arm C

Comparison groups

Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel v Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Number of subjects included in analysis

84

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6314

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

2.64

Secondary: Number of Participants with Adverse Events (AEs)

Top of page

End point title

Number of Participants with Adverse Events (AEs)

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety-evaluable population included all randomised participants who took at least one dose of the study treatment.

End point type

Secondary

End point timeframe

Up to 39 months

End point values	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel
Number of subjects analysed	43	43	41	58	57
Units: participants	42	43	40	58	56

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 39 months

Adverse event reporting additional description

Safety-evaluable population included all randomized participants who took at least one dose of the study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18

Reporting group title

Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel

Reporting group description

TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Reporting group title

Cohort 1 Arm C: Placebo + Placebo + Paclitaxel

Reporting group description

TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.

Serious adverse events	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel
Total subjects affected by serious adverse events
subjects affected / exposed	14 / 43 (32.56%)	7 / 43 (16.28%)	9 / 57 (15.79%)	16 / 58 (27.59%)	7 / 41 (17.07%)
number of deaths (all causes)	16	19	18	18	13
number of deaths resulting from adverse events	3	0	0	0	1
Vascular disorders
Hypotension
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
Fatigue
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vocal cord atrophy
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	2 / 58 (3.45%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	2 / 58 (3.45%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Pelvic fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Cardiac failure
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Nervous system disorders
Facial paralysis
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vocal cord paresis
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	2 / 58 (3.45%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 43 (4.65%)	1 / 43 (2.33%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	4 / 4	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal toxicity
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Drug eruption
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eczema
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	3 / 43 (6.98%)	1 / 43 (2.33%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	3 / 3	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphangitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	2 / 43 (4.65%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	2 / 43 (4.65%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	2 / 41 (4.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium colitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular device infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	0 / 57 (0.00%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 43 (2.33%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel	Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel	Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel	Cohort 1 Arm C: Placebo + Placebo + Paclitaxel
Total subjects affected by non serious adverse events
subjects affected / exposed	42 / 43 (97.67%)	42 / 43 (97.67%)	55 / 57 (96.49%)	56 / 58 (96.55%)	40 / 41 (97.56%)
Vascular disorders
Lymphoedema
subjects affected / exposed	3 / 43 (6.98%)	1 / 43 (2.33%)	1 / 57 (1.75%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences all number	3	1	1	1	0
Hypertension
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	1 / 57 (1.75%)	4 / 58 (6.90%)	2 / 41 (4.88%)
occurrences all number	0	1	1	5	2
General disorders and administration site conditions
Asthenia
subjects affected / exposed	9 / 43 (20.93%)	6 / 43 (13.95%)	5 / 57 (8.77%)	13 / 58 (22.41%)	7 / 41 (17.07%)
occurrences all number	10	8	5	24	9
Pain
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	1 / 57 (1.75%)	3 / 58 (5.17%)	3 / 41 (7.32%)
occurrences all number	0	1	1	3	4
Oedema peripheral
subjects affected / exposed	2 / 43 (4.65%)	1 / 43 (2.33%)	1 / 57 (1.75%)	4 / 58 (6.90%)	4 / 41 (9.76%)
occurrences all number	2	1	3	5	6
Fatigue
subjects affected / exposed	8 / 43 (18.60%)	10 / 43 (23.26%)	11 / 57 (19.30%)	14 / 58 (24.14%)	5 / 41 (12.20%)
occurrences all number	12	12	11	15	8
Pyrexia
subjects affected / exposed	6 / 43 (13.95%)	3 / 43 (6.98%)	7 / 57 (12.28%)	7 / 58 (12.07%)	1 / 41 (2.44%)
occurrences all number	6	5	8	10	2
Mucosal inflammation
subjects affected / exposed	6 / 43 (13.95%)	3 / 43 (6.98%)	6 / 57 (10.53%)	4 / 58 (6.90%)	0 / 41 (0.00%)
occurrences all number	7	3	7	5	0
Oedema
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	2 / 57 (3.51%)	4 / 58 (6.90%)	0 / 41 (0.00%)
occurrences all number	0	1	2	4	0
Illness
subjects affected / exposed	3 / 43 (6.98%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences all number	9	0	0	0	0
Malaise
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	0 / 57 (0.00%)	3 / 58 (5.17%)	1 / 41 (2.44%)
occurrences all number	0	1	0	3	1
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	0 / 43 (0.00%)	2 / 43 (4.65%)	2 / 57 (3.51%)	3 / 58 (5.17%)	4 / 41 (9.76%)
occurrences all number	0	2	2	3	4
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 43 (9.30%)	5 / 43 (11.63%)	3 / 57 (5.26%)	4 / 58 (6.90%)	0 / 41 (0.00%)
occurrences all number	4	5	4	5	0
Dyspnoea
subjects affected / exposed	2 / 43 (4.65%)	3 / 43 (6.98%)	3 / 57 (5.26%)	5 / 58 (8.62%)	4 / 41 (9.76%)
occurrences all number	3	3	3	5	4
Rhinorrhoea
subjects affected / exposed	4 / 43 (9.30%)	1 / 43 (2.33%)	1 / 57 (1.75%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences all number	4	1	1	1	0
Epistaxis
subjects affected / exposed	3 / 43 (6.98%)	1 / 43 (2.33%)	1 / 57 (1.75%)	1 / 58 (1.72%)	1 / 41 (2.44%)
occurrences all number	3	1	1	1	1
Pneumonitis
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	0	0	2	3	0
Psychiatric disorders
Insomnia
subjects affected / exposed	4 / 43 (9.30%)	6 / 43 (13.95%)	4 / 57 (7.02%)	6 / 58 (10.34%)	3 / 41 (7.32%)
occurrences all number	4	6	4	6	3
Anxiety
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	0	0	1	3	0
Investigations
Blood lactate dehydrogenase increased
subjects affected / exposed	1 / 43 (2.33%)	6 / 43 (13.95%)	0 / 57 (0.00%)	3 / 58 (5.17%)	1 / 41 (2.44%)
occurrences all number	1	14	0	7	1
Blood alkaline phosphatase increased
subjects affected / exposed	5 / 43 (11.63%)	6 / 43 (13.95%)	1 / 57 (1.75%)	6 / 58 (10.34%)	1 / 41 (2.44%)
occurrences all number	7	9	1	9	1
Gamma-glutamyltransferase increased
subjects affected / exposed	4 / 43 (9.30%)	2 / 43 (4.65%)	1 / 57 (1.75%)	6 / 58 (10.34%)	0 / 41 (0.00%)
occurrences all number	5	4	1	7	0
Weight decreased
subjects affected / exposed	4 / 43 (9.30%)	0 / 43 (0.00%)	1 / 57 (1.75%)	3 / 58 (5.17%)	1 / 41 (2.44%)
occurrences all number	4	0	1	3	2
Neutrophil count decreased
subjects affected / exposed	5 / 43 (11.63%)	9 / 43 (20.93%)	6 / 57 (10.53%)	9 / 58 (15.52%)	5 / 41 (12.20%)
occurrences all number	12	14	16	20	7
Lymphocyte count decreased
subjects affected / exposed	3 / 43 (6.98%)	1 / 43 (2.33%)	1 / 57 (1.75%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	16	9	1	10	0
Lipase increased
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	1 / 57 (1.75%)	5 / 58 (8.62%)	0 / 41 (0.00%)
occurrences all number	4	1	1	5	0
Aspartate aminotransferase increased
subjects affected / exposed	7 / 43 (16.28%)	10 / 43 (23.26%)	10 / 57 (17.54%)	11 / 58 (18.97%)	10 / 41 (24.39%)
occurrences all number	9	14	18	16	18
Blood creatinine increased
subjects affected / exposed	5 / 43 (11.63%)	2 / 43 (4.65%)	1 / 57 (1.75%)	5 / 58 (8.62%)	0 / 41 (0.00%)
occurrences all number	7	2	2	8	0
White blood cell count decreased
subjects affected / exposed	5 / 43 (11.63%)	6 / 43 (13.95%)	2 / 57 (3.51%)	4 / 58 (6.90%)	1 / 41 (2.44%)
occurrences all number	13	14	10	11	2
Alanine aminotransferase increased
subjects affected / exposed	11 / 43 (25.58%)	11 / 43 (25.58%)	11 / 57 (19.30%)	12 / 58 (20.69%)	12 / 41 (29.27%)
occurrences all number	15	12	18	19	15
Blood albumin decreased
subjects affected / exposed	1 / 43 (2.33%)	2 / 43 (4.65%)	0 / 57 (0.00%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	2	2	0	6	0
Amylase increased
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	2 / 57 (3.51%)	4 / 58 (6.90%)	0 / 41 (0.00%)
occurrences all number	0	0	2	4	0
Blood cholesterol increased
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	2 / 57 (3.51%)	4 / 58 (6.90%)	2 / 41 (4.88%)
occurrences all number	1	4	3	9	2
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 43 (0.00%)	2 / 43 (4.65%)	1 / 57 (1.75%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	0	4	1	3	0
Glycosylated haemoglobin increased
subjects affected / exposed	1 / 43 (2.33%)	2 / 43 (4.65%)	0 / 57 (0.00%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	1	2	0	3	0
Blood glucose increased
subjects affected / exposed	2 / 43 (4.65%)	2 / 43 (4.65%)	0 / 57 (0.00%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	2	4	0	4	0
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	1 / 43 (2.33%)	4 / 43 (9.30%)	1 / 57 (1.75%)	3 / 58 (5.17%)	1 / 41 (2.44%)
occurrences all number	1	5	1	8	1
Infusion related reaction
subjects affected / exposed	3 / 43 (6.98%)	1 / 43 (2.33%)	5 / 57 (8.77%)	8 / 58 (13.79%)	2 / 41 (4.88%)
occurrences all number	5	2	7	11	2
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 43 (9.30%)	4 / 43 (9.30%)	4 / 57 (7.02%)	5 / 58 (8.62%)	2 / 41 (4.88%)
occurrences all number	4	4	4	5	11
Headache
subjects affected / exposed	2 / 43 (4.65%)	6 / 43 (13.95%)	12 / 57 (21.05%)	11 / 58 (18.97%)	3 / 41 (7.32%)
occurrences all number	2	6	14	15	3
Dysgeusia
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	2 / 57 (3.51%)	7 / 58 (12.07%)	3 / 41 (7.32%)
occurrences all number	0	1	2	8	3
Neuropathy peripheral
subjects affected / exposed	15 / 43 (34.88%)	8 / 43 (18.60%)	8 / 57 (14.04%)	8 / 58 (13.79%)	10 / 41 (24.39%)
occurrences all number	19	9	9	8	11
Peripheral sensory neuropathy
subjects affected / exposed	4 / 43 (9.30%)	6 / 43 (13.95%)	9 / 57 (15.79%)	11 / 58 (18.97%)	5 / 41 (12.20%)
occurrences all number	4	7	10	11	6
Polyneuropathy
subjects affected / exposed	2 / 43 (4.65%)	3 / 43 (6.98%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences all number	2	3	0	0	0
Paraesthesia
subjects affected / exposed	5 / 43 (11.63%)	3 / 43 (6.98%)	1 / 57 (1.75%)	4 / 58 (6.90%)	3 / 41 (7.32%)
occurrences all number	6	3	1	5	3
Syncope
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	1 / 57 (1.75%)	3 / 58 (5.17%)	1 / 41 (2.44%)
occurrences all number	0	0	1	3	1
Neurotoxicity
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	2 / 57 (3.51%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	1	1	2	4	0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	4 / 43 (9.30%)	2 / 43 (4.65%)	4 / 57 (7.02%)	8 / 58 (13.79%)	2 / 41 (4.88%)
occurrences all number	5	2	7	13	6
Anaemia
subjects affected / exposed	15 / 43 (34.88%)	7 / 43 (16.28%)	12 / 57 (21.05%)	22 / 58 (37.93%)	6 / 41 (14.63%)
occurrences all number	22	18	17	36	10
Neutropenia
subjects affected / exposed	15 / 43 (34.88%)	5 / 43 (11.63%)	9 / 57 (15.79%)	11 / 58 (18.97%)	8 / 41 (19.51%)
occurrences all number	21	21	19	36	26
Lymphopenia
subjects affected / exposed	2 / 43 (4.65%)	0 / 43 (0.00%)	1 / 57 (1.75%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	3	0	1	6	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 43 (0.00%)	1 / 43 (2.33%)	3 / 57 (5.26%)	3 / 58 (5.17%)	1 / 41 (2.44%)
occurrences all number	0	1	3	3	1
Stomatitis
subjects affected / exposed	3 / 43 (6.98%)	6 / 43 (13.95%)	3 / 57 (5.26%)	7 / 58 (12.07%)	2 / 41 (4.88%)
occurrences all number	3	7	4	8	3
Dyspepsia
subjects affected / exposed	3 / 43 (6.98%)	3 / 43 (6.98%)	0 / 57 (0.00%)	6 / 58 (10.34%)	2 / 41 (4.88%)
occurrences all number	4	3	0	8	2
Vomiting
subjects affected / exposed	7 / 43 (16.28%)	10 / 43 (23.26%)	8 / 57 (14.04%)	8 / 58 (13.79%)	0 / 41 (0.00%)
occurrences all number	16	14	9	10	0
Abdominal pain upper
subjects affected / exposed	5 / 43 (11.63%)	0 / 43 (0.00%)	3 / 57 (5.26%)	5 / 58 (8.62%)	2 / 41 (4.88%)
occurrences all number	7	0	3	7	2
Abdominal pain
subjects affected / exposed	2 / 43 (4.65%)	4 / 43 (9.30%)	2 / 57 (3.51%)	4 / 58 (6.90%)	4 / 41 (9.76%)
occurrences all number	2	4	2	5	4
Diarrhoea
subjects affected / exposed	32 / 43 (74.42%)	30 / 43 (69.77%)	16 / 57 (28.07%)	37 / 58 (63.79%)	15 / 41 (36.59%)
occurrences all number	66	71	28	81	22
Nausea
subjects affected / exposed	17 / 43 (39.53%)	14 / 43 (32.56%)	13 / 57 (22.81%)	22 / 58 (37.93%)	9 / 41 (21.95%)
occurrences all number	21	16	16	36	10
Constipation
subjects affected / exposed	7 / 43 (16.28%)	12 / 43 (27.91%)	24 / 57 (42.11%)	16 / 58 (27.59%)	26 / 41 (63.41%)
occurrences all number	7	16	33	22	29
Gastritis
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	1 / 57 (1.75%)	1 / 58 (1.72%)	3 / 41 (7.32%)
occurrences all number	1	1	1	1	3
Dry mouth
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	0 / 57 (0.00%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	1	1	0	3	0
Abdominal discomfort
subjects affected / exposed	3 / 43 (6.98%)	0 / 43 (0.00%)	1 / 57 (1.75%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences all number	3	0	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 43 (6.98%)	2 / 43 (4.65%)	0 / 57 (0.00%)	2 / 58 (3.45%)	0 / 41 (0.00%)
occurrences all number	5	2	0	2	0
Hepatobiliary disorders
Hyperbilirubinaemia
subjects affected / exposed	3 / 43 (6.98%)	0 / 43 (0.00%)	0 / 57 (0.00%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences all number	4	0	0	0	0
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	2 / 43 (4.65%)	2 / 43 (4.65%)	3 / 57 (5.26%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences all number	2	2	3	0	0
Pruritus
subjects affected / exposed	3 / 43 (6.98%)	0 / 43 (0.00%)	8 / 57 (14.04%)	8 / 58 (13.79%)	5 / 41 (12.20%)
occurrences all number	4	0	8	9	6
Urticaria
subjects affected / exposed	4 / 43 (9.30%)	0 / 43 (0.00%)	3 / 57 (5.26%)	0 / 58 (0.00%)	0 / 41 (0.00%)
occurrences all number	4	0	3	0	0
Alopecia
subjects affected / exposed	10 / 43 (23.26%)	13 / 43 (30.23%)	25 / 57 (43.86%)	18 / 58 (31.03%)	19 / 41 (46.34%)
occurrences all number	10	13	26	18	19
Rash maculo-papular
subjects affected / exposed	1 / 43 (2.33%)	4 / 43 (9.30%)	0 / 57 (0.00%)	4 / 58 (6.90%)	0 / 41 (0.00%)
occurrences all number	1	5	0	4	0
Rash
subjects affected / exposed	10 / 43 (23.26%)	10 / 43 (23.26%)	17 / 57 (29.82%)	19 / 58 (32.76%)	7 / 41 (17.07%)
occurrences all number	11	15	35	27	11
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 43 (0.00%)	0 / 43 (0.00%)	4 / 57 (7.02%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences all number	0	0	5	1	0
Hypothyroidism
subjects affected / exposed	2 / 43 (4.65%)	2 / 43 (4.65%)	6 / 57 (10.53%)	6 / 58 (10.34%)	0 / 41 (0.00%)
occurrences all number	2	2	7	7	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	3 / 43 (6.98%)	4 / 43 (9.30%)	5 / 57 (8.77%)	5 / 58 (8.62%)	2 / 41 (4.88%)
occurrences all number	3	5	6	7	2
Arthralgia
subjects affected / exposed	4 / 43 (9.30%)	4 / 43 (9.30%)	4 / 57 (7.02%)	7 / 58 (12.07%)	3 / 41 (7.32%)
occurrences all number	4	5	9	8	3
Bone pain
subjects affected / exposed	2 / 43 (4.65%)	2 / 43 (4.65%)	1 / 57 (1.75%)	5 / 58 (8.62%)	2 / 41 (4.88%)
occurrences all number	2	3	2	5	2
Musculoskeletal pain
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	0 / 57 (0.00%)	0 / 58 (0.00%)	3 / 41 (7.32%)
occurrences all number	1	1	0	0	3
Myalgia
subjects affected / exposed	5 / 43 (11.63%)	3 / 43 (6.98%)	5 / 57 (8.77%)	9 / 58 (15.52%)	8 / 41 (19.51%)
occurrences all number	5	3	5	26	9
Infections and infestations
Urinary tract infection
subjects affected / exposed	3 / 43 (6.98%)	4 / 43 (9.30%)	2 / 57 (3.51%)	3 / 58 (5.17%)	2 / 41 (4.88%)
occurrences all number	3	4	3	3	8
COVID-19
subjects affected / exposed	2 / 43 (4.65%)	2 / 43 (4.65%)	3 / 57 (5.26%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences all number	2	2	3	1	0
Metabolism and nutrition disorders
Hypocalcaemia
subjects affected / exposed	1 / 43 (2.33%)	3 / 43 (6.98%)	1 / 57 (1.75%)	1 / 58 (1.72%)	0 / 41 (0.00%)
occurrences all number	4	3	1	1	0
Decreased appetite
subjects affected / exposed	6 / 43 (13.95%)	6 / 43 (13.95%)	7 / 57 (12.28%)	16 / 58 (27.59%)	6 / 41 (14.63%)
occurrences all number	7	6	9	20	7
Hyperkalaemia
subjects affected / exposed	1 / 43 (2.33%)	1 / 43 (2.33%)	3 / 57 (5.26%)	2 / 58 (3.45%)	1 / 41 (2.44%)
occurrences all number	1	1	4	4	1
Hypertriglyceridaemia
subjects affected / exposed	0 / 43 (0.00%)	5 / 43 (11.63%)	1 / 57 (1.75%)	5 / 58 (8.62%)	0 / 41 (0.00%)
occurrences all number	0	11	1	5	0
Hypokalaemia
subjects affected / exposed	4 / 43 (9.30%)	0 / 43 (0.00%)	1 / 57 (1.75%)	6 / 58 (10.34%)	1 / 41 (2.44%)
occurrences all number	6	0	1	8	1
Hyperglycaemia
subjects affected / exposed	10 / 43 (23.26%)	4 / 43 (9.30%)	3 / 57 (5.26%)	12 / 58 (20.69%)	2 / 41 (4.88%)
occurrences all number	12	9	4	18	2
Hyponatraemia
subjects affected / exposed	2 / 43 (4.65%)	1 / 43 (2.33%)	0 / 57 (0.00%)	4 / 58 (6.90%)	2 / 41 (4.88%)
occurrences all number	2	1	0	5	2
Hypomagnesaemia
subjects affected / exposed	3 / 43 (6.98%)	0 / 43 (0.00%)	1 / 57 (1.75%)	1 / 58 (1.72%)	2 / 41 (4.88%)
occurrences all number	3	0	1	1	2
Hypernatraemia
subjects affected / exposed	1 / 43 (2.33%)	2 / 43 (4.65%)	0 / 57 (0.00%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	2	2	0	6	0
Dehydration
subjects affected / exposed	0 / 43 (0.00%)	2 / 43 (4.65%)	0 / 57 (0.00%)	3 / 58 (5.17%)	0 / 41 (0.00%)
occurrences all number	0	2	0	3	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

13 Sep 2019

Amendment 1: 1. Disease-specific inclusion criteria was updated to include a criterion that a participant must be an appropriate candidate for paclitaxel monotherapy if tumor PD-L1 status is unknown and if tumor status is known to be PD-L1 positive, the participant should be an appropriate candidate for atezolizumab+paclitaxel. 2. General exclusion criteria was updated to include a criterion that a participant must not be on current treatment with medications used at doses known to cause clinically relevant prolongation of QT/corrected QT (QTc) interval. 3. Disease-specific exclusion criteria have been updated to include a criterion that a participant must not have known germline breast cancer gene (BRCA)1/2 deleterious mutation. 4. The Optional Interim Analyses section (Section 6.9.3) was removed.

20 Sep 2019

Amendment 2: 1. Enrolment number was updated from 1150 to 1155 participants, with a change from approximately 520 to approximately 525 participants in Cohort 1. The allocation of participants between arms in Cohort 1 was made equal, to support the independent testing of Arm A vs. Arm C, and Arm B vs. Arm C.

18 Aug 2020

Amendment 3: 1. The study rationale and benefit-risk assessment was updated to indicate that based on results from the primary analysis of the MO39196 study, the control arm for Cohort 2 of this Study CO41101 (atezolizumab plus paclitaxel plus placebo for ipatasertib) was no longer considered appropriate. As of 6 August 2020, further enrollment in Cohort 2 was suspended, and all participants in Cohort 2 were unblinded to treatment assignment.

21 Dec 2020

Amendment 4: 1. Section 1.2 was updated to include the outcome of the primary analysis of the CO40016 study and rationale for termination of enrollment and unblinding of Cohort 1 of Study CO41101. 2. Study was updated to indicate that based on results from the primary analysis of the CO40016 study in TNBC, Arm B for Cohort 1 of this Study CO41101 (ipatasertib plus paclitaxel plus placebo for atezolizumab) was no longer considered appropriate. As of 18 September 2020, further enrollment in Cohort 1 was terminated, and all participants in Cohort 1 were unblinded to treatment assignment on 21 September 2020. 3. All secondary efficacy objectives and pharmacokinetic and immunogenicity objectives were moved to exploratory objectives. 4. The total length of the study was changed to 2-3 years.

25 Feb 2022

Amendment 5: 1. Benefit-risk assessment and guidance on concomitant administration of severe acute respiratory syndrome coronavirus 2 vaccines with atezolizumab was added.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Thu May 02 02:48:13 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands