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Clinical Trial Results:
A Phase II, Multicenter, Single-Arm Study of Atezolizumab (MPDL3280A) in Patients with PD-L1Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Summary
EudraCT number	2013-000177-69
Trial protocol	BE GB NL FR
Global end of trial date	18 Dec 2017

Results information
Results version number	v2(current)
This version publication date	02 Jan 2019
First version publication date	04 Nov 2016
Other versions	v1
Version creation reason	New data added to full data set Final CSR updates

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

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Trial information

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Sponsor protocol code

GO28625

ISRCTN number

US NCT number

NCT01846416

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG., +41 61 6878333, global.trial_information@roche.com

Scientific contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG., +41 61 6878333, global.trial_information@roche.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

18 Dec 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Dec 2017

Was the trial ended prematurely?

Main objective of the trial

This is Phase II, global, multicenter, single-arm trial designed to evaluate the efficacy and safety of atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-programmed death-ligand 1 (PD-L1) antibody in PD-L1-selected participants with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary objective for this study was to evaluate the efficacy of atezolizumab in participants with PD-L1−positive locally advanced or metastatic NSCLC, as measured by investigator-assessed objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (RECIST).

Protection of trial subjects

The study was conducted in accordance with the principles of the "Declaration of Helsinki" and Good Clinical Practice (GCP) according to the regulations and procedures described in the protocol. All the investigators were trained according to the applicable Sponsor standard operating procedures, and strictly adhered to the stated provisions. This was documented by investigator's signature on the protocol agreeing to carry out all of its terms in accordance with the applicable regulations and to follow International Conference on Harmonization (ICH) GCP guidelines. Approval from Institutional Review Boards (IRBs) and Ethics Committee (EC) was obtained before study start and was documented in a letter to investigator specifying the date the committee met, and granted approval. Approval from relevant competent authority was also obtained prior to starting the study. Protocol amendments were prepared by the Sponsor, and were submitted to IRB/EC and to Regulatory Authorities in accordance with the local regulatory requirements. Audits were performed by the Sponsor Quality Assurance group in compliance with GCP.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 May 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 7

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

Netherlands: 6

Country: Number of subjects enrolled

United States: 108

Worldwide total number of subjects

137

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Overall 201 participants were screened for clinical eligibility, out of which 63 participants were screen failures, and hence 138 participants were enrolled, and 137 participants received treatment as one US subject was withdrawn from the study prior to study treatment.

Period 1 title

Treatment Phase (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Atezolizumab (MPDL3280) : 1L Participants

Arm description

Participants with no prior chemotherapy for advanced NSCLC disease received atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

MPDL3280A, Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab as a fixed dose of 1200-mg IV infusion on Day 1 of each 21-day cycle. The initial dose of atezolizumab was delivered over 60 (± 15) minutes. If the first infusion was tolerated without infusion-associated adverse events, the second infusion could be delivered over 30 (± 10) minutes. If the 30-minute infusion was well tolerated, all subsequent infusions could be delivered over 30 (± 10) minutes.

Atezolizumab (MPDL3280): 2L+ Participants

Arm description

Participants who had progressed during or following a prior platinum-based chemotherapy regimen without restriction to maximum number of prior therapies received atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until no longer deemed to be experiencing clinical benefit as assessed by the investigator.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

MPDL3280A, Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab as a fixed dose of 1200-mg IV infusion on Day 1 of each 21-day cycle. If the first infusion was tolerated without infusion-associated adverse events, the second infusion could be delivered over 30 (± 10) minutes. If the 30-minute infusion was well tolerated, all subsequent infusions could be delivered over 30 (± 10) minutes.

Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants

Arm description

Participants with previously treated brain metastases and who had progressed during or following a prior platinum-based chemotherapy regimen without restriction to the maximum number of prior therapies, received atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until no longer deemed to be experiencing clinical benefit as assessed by the investigator.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

MPDL3280A, Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Started	31	93	13
Completed	0	0	0
Not completed	31	93	13
Physician decision	1	2	-
Consent withdrawn by subject	2	4	2
Adverse event, non-fatal	3	4	-
Death	2	9	1
Progressive Disease	21	63	9
Non-compliance	-	2	-
Unspecified	1	5	1
Study Terminated by Sponsor	1	4	-

Baseline characteristics

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Reporting group title

Atezolizumab (MPDL3280) : 1L Participants

Reporting group description

Participants with no prior chemotherapy for advanced NSCLC disease received atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until disease progression.

Reporting group title

Atezolizumab (MPDL3280): 2L+ Participants

Reporting group description

Reporting group title

Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants

Reporting group description

Reporting group values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants	Total
Number of subjects	31	93	13	137
Age categorical
Units: Subjects
In utero				0
Preterm newborn infants (gestational age < 37 wks)				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)				0
From 65-84 years				0
85 years and over				0
Age Continuous
Units: years
arithmetic mean (standard deviation)	68.0 ± 10.8	65.2 ± 9.3	63.8 ± 7.7	-
Gender, Male/Female
Units: Subjects
Female	17	34	7	58
Male	14	59	6	79
Age Continuous
Units: Years
arithmetic mean (standard deviation)	68.0 ± 10.8	65.2 ± 9.3	63.8 ± 7,7	-

Subject analysis set title

Atezolizumab (MPDL3280) : All Arms

Subject analysis set type

Intention-to-treat

Subject analysis set description

The PK-evaluable population was defined as patients who received any dose of atezolizumab treatment and had PK data at timepoints that were sufficient to determine PK parameters.

Subject analysis sets values	Atezolizumab (MPDL3280) : All Arms
Number of subjects	135
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age Continuous
Units: years
arithmetic mean (standard deviation)	63.8 ± 7,7
Gender, Male/Female
Units: Subjects
Female
Male
Age Continuous
Units: Years
arithmetic mean (standard deviation)	65.7 ± 9.6

End points

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Reporting group title

Atezolizumab (MPDL3280) : 1L Participants

Reporting group description

Participants with no prior chemotherapy for advanced NSCLC disease received atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until disease progression.

Reporting group title

Atezolizumab (MPDL3280): 2L+ Participants

Reporting group description

Reporting group title

Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants

Reporting group description

Subject analysis set title

Atezolizumab (MPDL3280) : All Arms

Subject analysis set type

Intention-to-treat

Subject analysis set description

The PK-evaluable population was defined as patients who received any dose of atezolizumab treatment and had PK data at timepoints that were sufficient to determine PK parameters.

Primary: Percentage of Participants with Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)

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End point title

Percentage of Participants with Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) ^[1]

End point description

Objective response was defined as a complete response (CR) or partial response (PR), as determined by investigator according to modified RECIST criteria. Modified RECIST was derived from RECIST v1.1 conventions and immune related response criteria. CR was defined as disappearance of all tumor lesions (target lesion [TL] and non-target lesion [non-TL]) and no new measurable or unmeasurable lesions, all lymph node short axes must be less than 10 millimeters (mm), and PR was defined as at least 30 percent (%) decrease in sum of diameter of TLs, and all new measurable lesions to baseline in absence of CR, and both confirmed by consecutive assessment greater than or equal to 4 weeks from date first documented. Participants not meeting these criteria, including participants without at least one post-baseline response assessment were considered as non-responders.

End point type

Primary

End point timeframe

Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The study was of an explorative nature; therefore only descriptive statistical methods were applied, and no formal statistical hypothesis testing was planned.

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	92	13
Units: percentage of participants
number (confidence interval 95%)	32 (17 to 51)	21 (13 to 30)	23 (5 to 54)

No statistical analyses for this end point

Secondary: Percentage of Participants with Objective Response According to RECIST Version 1.1 (v1.1)

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End point title

Percentage of Participants with Objective Response According to RECIST Version 1.1 (v1.1)

End point description

Objective response was defined as a CR or PR, as determined by the investigator according to RECIST v1.1. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must had reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of TLs, taking as reference the baseline sum of diameters, in absence of CR. For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Participants not meeting these criteria, including participants without at least 1 post-baseline response assessment were considered as non-responders.

End point type

Secondary

End point timeframe

Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months)

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	92	13
Units: percentage of participants
number (confidence interval 95%)	29 (14 to 48)	19 (11 to 28)	23 (5 to 54)

No statistical analyses for this end point

Secondary: Duration of Objective Response According to RECIST v1.1

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End point title

Duration of Objective Response According to RECIST v1.1

End point description

Duration of objective response was defined as time from initial occurrence of documented CR or PR until documented disease progression (using RECIST v1.1 as determined by investigator) or death, whichever occurred first. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must had reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameter of TLs, taking as reference baseline sum of diameters, in absence of CR. Progressive disease (PD) was at least a 20% increase in sum of diameters of TLs, taking as reference smallest sum on study (nadir). For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Participants were censored at the date of last tumor assessment. '3.33333' signifies that the median was not evaluable.

End point type

Secondary

End point timeframe

Baseline, and Day 1 of Cycle 1 (21-day cycle), then every 6 weeks for the first 12 months and then every 9 weeks thereafter until disease progression (up to 20 months)

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	9	17	3
Units: months
median (full range (min-max))	9.2 (2.3 to 30.4)	17.0 (2.8 to 44.2)	3.33333 (2.8 to 9.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with 6-Month Duration of Objective Response

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End point title

Percentage of Participants with 6-Month Duration of Objective Response

End point description

Duration of objective response at 6 months was defined as time from initial occurrence of documented CR or PR until Month 6. For TLs, CR was defined as disappearance of all TLs. Any pathological lymph nodes, whether target or non-target, must have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in sum of diameter of TLs, taking as reference baseline sum of diameters, in absence of CR. For non-TLs, CR was defined as disappearance of all non-TLs and if applicable, normalization of tumor marker level. Participants were censored at the date of last tumor assessment.

End point type

Secondary

End point timeframe

Month 6

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	8	15	3
Units: percentage of participants
number (not applicable)	75.0	91.7	66.7

No statistical analyses for this end point

Secondary: Percentage of Participants with Disease Progression or Death According to RECIST v1.1

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End point title

Percentage of Participants with Disease Progression or Death According to RECIST v1.1

End point description

For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.

End point type

Secondary

End point timeframe

Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: percentage of participants
number (not applicable)	75.0	91.7	66.7

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) According to RECIST v1.1

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End point title

Progression-Free Survival (PFS) According to RECIST v1.1

End point description

PFS was defined as time from randomization to first occurrence of documented disease progression (based on RECIST v1.1 criteria) or death due to any cause within 30 days of the last treatment, whichever occurs earlier as determined by investigator. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameter of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. In event of no disease progression or documented death, PFS was censored at date of last evaluable tumor assessment. Participants with no post-baseline tumor assessments were censored at the time of first dose plus 1 day.

End point type

Secondary

End point timeframe

Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: months
median (full range (min-max))	4.5 (0.9 to 37.9)	2.7 (0.0 to 45.5)	2.5 (1.0 to 11.3)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1

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End point title

Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1

End point description

Percentage of participants who were progression free at Month 6 and 12 (based on RECIST v1.1) was reported. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameter of TLs, taking as reference the smallest sum on study (nadir). For non-TLs, progressive disease was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. '99999' signifies that the value was not estimable.

End point type

Secondary

End point timeframe

Months 6, 12 and 30

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: percentage of participants
number (not applicable)
Month 6	33.50	32.29	15.38
Month 12	20	23	99999
Month 30	13	10	99999

No statistical analyses for this end point

Secondary: Percentage of Participants with Disease Progression or Death According to Modified RECIST

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End point title

Percentage of Participants with Disease Progression or Death According to Modified RECIST

End point description

For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started.

End point type

Secondary

End point timeframe

Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: percentage of participants
number (not applicable)	58.1	66.7	69.2

No statistical analyses for this end point

Secondary: PFS According to Modified RECIST

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End point title

PFS According to Modified RECIST

End point description

PFS according to modified RECIST was defined as time from first dose of atezolizumab to first occurrence of documented disease progression or death due to any cause, as determined by investigator for participants who discontinued at first documented radiographic progression. For participants who continued beyond first documented progression and had follow-up tumor assessment or death, PFS was defined as time from first dose of atezolizumab to subsequent radiographic progression or death. For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started. In event of no disease progression or documented death, PFS was censored at date of last evaluable tumor assessment.

End point type

Secondary

End point timeframe

Baseline to the first occurrence of progression or death, whichever occurs earlier (up to 20 months)

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: months
median (full range (min-max))	5.5 (0.9 to 37.9)	3.7 (0.0 to 45.5)	4.3 (1.1 to 16.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to Modified RECIST

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End point title

Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to Modified RECIST

End point description

Percentage of participants who were progression free at Months 6 and 12 (according to modified RECIST). For TLs, progressive disease was defined as at least a 20% increase in the sum of diameters of TLs and new measurable lesions, taking as reference the smallest sum recorded since treatment started. '99999' signifies a value that was not estimable.

End point type

Secondary

End point timeframe

Months 6, 12 and 30

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: percentage of participants
number (not applicable)
Month 6	43.12	39.10	44.87
Month 12	31	29	24
Month 30	12	10	99999

No statistical analyses for this end point

Secondary: Percentage of Participants with Death

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End point title

Percentage of Participants with Death

End point description

Participants were followed for survival throughout the study.

End point type

Secondary

End point timeframe

Baseline till death or up to 20 months, whichever occurred first

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: percentage of participants
number (not applicable)	74.2	76.3	76.9

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

OS was defined as the time from first dose of the study drug to the time of death from any cause of the study. Participants who were still alive at the time of analysis were censored at the time of their last study assessment (for active participants) or at the last date known alive (for participants in follow-up). If no post-baseline data were available, OS was censored at the date of first treatment plus 1 day.

End point type

Secondary

End point timeframe

Baseline till death or up to 20 months, whichever occurred first

End point values	Atezolizumab (MPDL3280) : 1L Participants	Atezolizumab (MPDL3280): 2L+ Participants	Atezolizumab (MPDL3280): 2L+ Brain Metastases Participants
Number of subjects analysed	31	93	13
Units: months
median (confidence interval 95%)	14.4 (12.8 to 22.1)	9.3 (5.8 to 17.6)	6.8 (3.2 to 19.5)

No statistical analyses for this end point

Secondary: Maximum Plasma Concentration (Cmax) for Atezolizumab

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End point title

Maximum Plasma Concentration (Cmax) for Atezolizumab

End point description

Pharmacokinetic- evaluable population: All treated participants with pharmacokinetic data at specified time points. Here, Number of participants analyzed = number of participants with available data for this outcome. Per planned analysis, pharmacokinetic data were not analyzed separately for each cohort.

End point type

Secondary

End point timeframe

Pre-dose (0 hour) and 30 minutes after infusion on Day 1 of Cycle 1

End point values	Atezolizumab (MPDL3280) : All Arms
Number of subjects analysed	135
Units: micrograms per milliliter (mcg/mL)
geometric mean (geometric coefficient of variation)	405 ± 31.7

No statistical analyses for this end point

Secondary: Minimum Plasma Concentration (Cmin) for Atezolizumab

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End point title

Minimum Plasma Concentration (Cmin) for Atezolizumab

End point description

Pharmacokinetic- evaluable population. Here, Number of participants analyzed = number of participants with available data for this outcome, and n= number of participants with available data at the specified time point. Per planned analysis, pharmacokinetic data were not analyzed separately for each cohort. '99999' signifies a value that was not evaluable.

End point type

Secondary

End point timeframe

Pre-dose (0 hour) on Day 1 of Cycles 2, 3, 4, 8, and 16

End point values	Atezolizumab (MPDL3280) : All Arms
Number of subjects analysed	125
Units: mcg/mL
geometric mean (geometric coefficient of variation)
Pre-dose Cycle 2 (Day 1) (n= 125)\|	68.8 ± 55.3
Pre-dose Cycle 3 (Day 1) (n= 100)\|	90.6 ± 136.6
Pre-dose Cycle 4 (Day 1) (n= 92)\|	123 ± 136.9
Pre-dose Cycle 8 (Day 1) (n= 51)\|	206 ± 45.9
Pre-dose Cycle 16 (Day 1) (n= 1)\|	135 ± 99999

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline until 20 months.

Adverse event reporting additional description

All participants who received at least one dose of atezolizumab were included in analysis.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Atezolizumab (MPDL3280A) : 1L Participants

Reporting group description

Participants with no prior chemotherapy for advanced NSCLC disease received atezolizumab IV as a fixed dose of 1200-mg on Day 1 of each 21-day cycle until disease progression.

Reporting group title

Atezolizumab (MPDL3280A) : 2L+ Brain Metastases Participants

Reporting group description

Reporting group title

Atezolizumab (MPDL3280A) : 2L+ Participants

Reporting group description

Serious adverse events	Atezolizumab (MPDL3280A) : 1L Participants	Atezolizumab (MPDL3280A) : 2L+ Brain Metastases Participants	Atezolizumab (MPDL3280A) : 2L+ Participants
Total subjects affected by serious adverse events
subjects affected / exposed	17 / 31 (54.84%)	6 / 13 (46.15%)	46 / 93 (49.46%)
number of deaths (all causes)	23	10	71
number of deaths resulting from adverse events
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Jugular vein thrombosis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 31 (0.00%)	2 / 13 (15.38%)	2 / 93 (2.15%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	6 / 93 (6.45%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	3 / 31 (9.68%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 3	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary haemorrhage
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchial obstruction
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchostenosis
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory disorder
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFLUENZA B VIRUS TEST POSITIVE
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac tamponade
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericarditis constrictive
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
CARDIAC FAILURE CONGESTIVE
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PALPITATIONS
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Guillain-Barre Syndrome
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intracranial venous sinus thrombosis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Monoparesis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vocal cord paralysis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Disseminated intravascular coagulation
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Amaurosis fugax
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Photopsia
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal wall haematoma
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
AUTOIMMUNE COLITIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLITIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thyroiditis acute
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	3 / 93 (3.23%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PAIN IN EXTREMITY
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	3 / 31 (9.68%)	0 / 13 (0.00%)	8 / 93 (8.60%)
occurrences causally related to treatment / all	1 / 4	0 / 0	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abscess neck
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes zoster disseminated
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERKALAEMIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPONATRAEMIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Atezolizumab (MPDL3280A) : 1L Participants	Atezolizumab (MPDL3280A) : 2L+ Brain Metastases Participants	Atezolizumab (MPDL3280A) : 2L+ Participants
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 31 (100.00%)	13 / 13 (100.00%)	88 / 93 (94.62%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 31 (0.00%)	2 / 13 (15.38%)	4 / 93 (4.30%)
occurrences all number	0	4	6
Vascular disorders
Hypotension
subjects affected / exposed	3 / 31 (9.68%)	0 / 13 (0.00%)	9 / 93 (9.68%)
occurrences all number	4	0	10
Hypertension
subjects affected / exposed	3 / 31 (9.68%)	1 / 13 (7.69%)	3 / 93 (3.23%)
occurrences all number	3	1	3
Hot flush
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	2 / 93 (2.15%)
occurrences all number	0	1	3
Haematoma
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	16 / 31 (51.61%)	5 / 13 (38.46%)	38 / 93 (40.86%)
occurrences all number	21	6	52
Pyrexia
subjects affected / exposed	7 / 31 (22.58%)	1 / 13 (7.69%)	21 / 93 (22.58%)
occurrences all number	8	1	23
Oedema peripheral
subjects affected / exposed	3 / 31 (9.68%)	2 / 13 (15.38%)	14 / 93 (15.05%)
occurrences all number	4	4	15
Chest pain
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	9 / 93 (9.68%)
occurrences all number	1	0	9
Pain
subjects affected / exposed	3 / 31 (9.68%)	2 / 13 (15.38%)	2 / 93 (2.15%)
occurrences all number	5	2	2
Asthenia
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	9 / 93 (9.68%)
occurrences all number	1	0	11
Chills
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	5 / 93 (5.38%)
occurrences all number	1	1	5
Influenza like illness
subjects affected / exposed	3 / 31 (9.68%)	1 / 13 (7.69%)	4 / 93 (4.30%)
occurrences all number	6	1	4
Malaise
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	6 / 93 (6.45%)
occurrences all number	0	0	6
Gait disturbance
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	2	0
General physical health deterioration
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Reproductive system and breast disorders
Breast swelling
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	1	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	5 / 31 (16.13%)	3 / 13 (23.08%)	33 / 93 (35.48%)
occurrences all number	6	5	47
Dyspnoea
subjects affected / exposed	8 / 31 (25.81%)	3 / 13 (23.08%)	30 / 93 (32.26%)
occurrences all number	9	4	35
Productive cough
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	13 / 93 (13.98%)
occurrences all number	2	0	14
Wheezing
subjects affected / exposed	3 / 31 (9.68%)	2 / 13 (15.38%)	7 / 93 (7.53%)
occurrences all number	3	2	10
Dysphonia
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	6 / 93 (6.45%)
occurrences all number	1	1	7
Haemoptysis
subjects affected / exposed	3 / 31 (9.68%)	1 / 13 (7.69%)	6 / 93 (6.45%)
occurrences all number	3	1	7
Nasal congestion
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	6 / 93 (6.45%)
occurrences all number	3	0	9
Pleural effusion
subjects affected / exposed	2 / 31 (6.45%)	2 / 13 (15.38%)	5 / 93 (5.38%)
occurrences all number	2	2	5
Pulmonary embolism
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	5 / 93 (5.38%)
occurrences all number	1	0	5
Dyspnoea exertional
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	1
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences all number	2	0	0
OROPHARYNGEAL PAIN
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	5 / 93 (5.38%)
occurrences all number	3	0	5
Psychiatric disorders
Insomnia
subjects affected / exposed	4 / 31 (12.90%)	1 / 13 (7.69%)	11 / 93 (11.83%)
occurrences all number	4	1	12
Anxiety
subjects affected / exposed	0 / 31 (0.00%)	2 / 13 (15.38%)	11 / 93 (11.83%)
occurrences all number	0	2	14
Depression
subjects affected / exposed	3 / 31 (9.68%)	1 / 13 (7.69%)	9 / 93 (9.68%)
occurrences all number	4	1	17
Confusional state
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	4 / 93 (4.30%)
occurrences all number	1	1	5
Hallucination
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	2 / 93 (2.15%)
occurrences all number	0	1	2
Investigations
Weight decreased
subjects affected / exposed	6 / 31 (19.35%)	1 / 13 (7.69%)	9 / 93 (9.68%)
occurrences all number	7	1	9
Alanine aminotransferase increased
subjects affected / exposed	2 / 31 (6.45%)	2 / 13 (15.38%)	2 / 93 (2.15%)
occurrences all number	2	2	2
Aspartate aminotransferase increased
subjects affected / exposed	2 / 31 (6.45%)	2 / 13 (15.38%)	3 / 93 (3.23%)
occurrences all number	2	2	3
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	1
Haemoglobin decreased
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	1	1	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
LYMPHOCYTE COUNT DECREASED
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	3 / 93 (3.23%)
occurrences all number	4	0	9
Injury, poisoning and procedural complications
FALL
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	6 / 93 (6.45%)
occurrences all number	1	0	9
JAW FRACTURE
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
LACERATION
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
LIMB INJURY
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	3 / 93 (3.23%)
occurrences all number	0	1	3
Atrial fibrillation
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences all number	2	0	2
Pericardial effusion
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	2 / 93 (2.15%)
occurrences all number	0	1	2
Aortic valve thickening
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	5 / 31 (16.13%)	3 / 13 (23.08%)	10 / 93 (10.75%)
occurrences all number	6	3	15
Dizziness
subjects affected / exposed	4 / 31 (12.90%)	1 / 13 (7.69%)	8 / 93 (8.60%)
occurrences all number	4	2	12
Dysgeusia
subjects affected / exposed	4 / 31 (12.90%)	0 / 13 (0.00%)	4 / 93 (4.30%)
occurrences all number	4	0	6
Peripheral sensory neuropathy
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	1
Cognitive disorder
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Hemiparesis
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	0
Memory impairment
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	1
Nystagmus
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Syncope
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
PARAESTHESIA
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	4 / 93 (4.30%)
occurrences all number	2	0	4
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	6 / 31 (19.35%)	1 / 13 (7.69%)	19 / 93 (20.43%)
occurrences all number	7	2	29
Neutropenia
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences all number	4	0	2
Thrombocytopenia
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	1	1	0
Lymphadenopathy
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	1	1	1
Deafness bilateral
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Ear pain
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Vestibular disorder
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
EXCESSIVE CERUMEN PRODUCTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Eye disorders
Diplopia
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	2 / 93 (2.15%)
occurrences all number	0	1	3
Lacrimation increased
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	2 / 93 (2.15%)
occurrences all number	0	1	2
Vision blurred
subjects affected / exposed	2 / 31 (6.45%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	3	1	1
Periorbital oedema
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	2	0
CONJUNCTIVAL HYPERAEMIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	1	1	2
Gastrointestinal disorders
Nausea
subjects affected / exposed	11 / 31 (35.48%)	4 / 13 (30.77%)	27 / 93 (29.03%)
occurrences all number	14	4	30
Constipation
subjects affected / exposed	8 / 31 (25.81%)	6 / 13 (46.15%)	16 / 93 (17.20%)
occurrences all number	10	9	22
Diarrhoea
subjects affected / exposed	8 / 31 (25.81%)	4 / 13 (30.77%)	17 / 93 (18.28%)
occurrences all number	12	6	23
Vomiting
subjects affected / exposed	4 / 31 (12.90%)	3 / 13 (23.08%)	14 / 93 (15.05%)
occurrences all number	4	3	25
Dysphagia
subjects affected / exposed	2 / 31 (6.45%)	1 / 13 (7.69%)	8 / 93 (8.60%)
occurrences all number	2	1	9
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	7 / 93 (7.53%)
occurrences all number	2	0	9
Abdominal pain
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	7 / 93 (7.53%)
occurrences all number	2	0	7
Dyspepsia
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	3 / 93 (3.23%)
occurrences all number	0	1	3
Abdominal pain upper
subjects affected / exposed	2 / 31 (6.45%)	1 / 13 (7.69%)	5 / 93 (5.38%)
occurrences all number	2	1	6
Mouth swelling
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
ABDOMINAL PAIN LOWER
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	3 / 93 (3.23%)
occurrences all number	0	1	3
STOMATITIS
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	3 / 93 (3.23%)
occurrences all number	2	0	3
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	5 / 31 (16.13%)	1 / 13 (7.69%)	9 / 93 (9.68%)
occurrences all number	8	1	13
Dry skin
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	12 / 93 (12.90%)
occurrences all number	1	0	13
Night sweats
subjects affected / exposed	2 / 31 (6.45%)	1 / 13 (7.69%)	7 / 93 (7.53%)
occurrences all number	2	1	9
Rash
subjects affected / exposed	3 / 31 (9.68%)	1 / 13 (7.69%)	9 / 93 (9.68%)
occurrences all number	8	1	15
Decubitus ulcer
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences all number	2	0	0
Acne
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Dermatitis
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	1
RASH MACULO-PAPULAR
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	3 / 93 (3.23%)
occurrences all number	2	0	5
Endocrine disorders
Hypothyroidism
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	3 / 93 (3.23%)
occurrences all number	1	1	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	6 / 31 (19.35%)	2 / 13 (15.38%)	18 / 93 (19.35%)
occurrences all number	8	2	23
Back pain
subjects affected / exposed	4 / 31 (12.90%)	2 / 13 (15.38%)	19 / 93 (20.43%)
occurrences all number	5	2	20
Pain in extremity
subjects affected / exposed	2 / 31 (6.45%)	1 / 13 (7.69%)	8 / 93 (8.60%)
occurrences all number	3	2	8
Musculoskeletal pain
subjects affected / exposed	4 / 31 (12.90%)	1 / 13 (7.69%)	9 / 93 (9.68%)
occurrences all number	4	1	9
Musculoskeletal chest pain
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	8 / 93 (8.60%)
occurrences all number	2	0	8
Myalgia
subjects affected / exposed	3 / 31 (9.68%)	1 / 13 (7.69%)	5 / 93 (5.38%)
occurrences all number	5	1	5
Neck pain
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	5 / 93 (5.38%)
occurrences all number	2	0	7
Bone pain
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	3 / 93 (3.23%)
occurrences all number	0	1	3
Muscle spasms
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	4 / 93 (4.30%)
occurrences all number	0	1	4
FLANK PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	5 / 93 (5.38%)
occurrences all number	0	0	6
MUSCULAR WEAKNESS
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	4 / 93 (4.30%)
occurrences all number	2	0	4
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	17 / 93 (18.28%)
occurrences all number	3	0	23
Pneumonia
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	8 / 93 (8.60%)
occurrences all number	1	0	8
Urinary tract infection
subjects affected / exposed	7 / 31 (22.58%)	2 / 13 (15.38%)	3 / 93 (3.23%)
occurrences all number	12	2	5
Candida infection
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 93 (1.08%)
occurrences all number	2	0	5
Cystitis
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 93 (0.00%)
occurrences all number	2	0	0
Fungal skin infection
subjects affected / exposed	1 / 31 (3.23%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	1	1	1
Influenza
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 93 (0.00%)
occurrences all number	0	1	0
Respiratory tract infection
subjects affected / exposed	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 93 (1.08%)
occurrences all number	0	1	1
SINUSITIS
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	2 / 93 (2.15%)
occurrences all number	2	0	3
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	6 / 31 (19.35%)	2 / 13 (15.38%)	22 / 93 (23.66%)
occurrences all number	7	2	28
Hypokalaemia
subjects affected / exposed	2 / 31 (6.45%)	4 / 13 (30.77%)	12 / 93 (12.90%)
occurrences all number	4	5	24
Hyponatraemia
subjects affected / exposed	3 / 31 (9.68%)	0 / 13 (0.00%)	12 / 93 (12.90%)
occurrences all number	7	0	20
Dehydration
subjects affected / exposed	2 / 31 (6.45%)	1 / 13 (7.69%)	7 / 93 (7.53%)
occurrences all number	4	1	8
Hypomagnesaemia
subjects affected / exposed	0 / 31 (0.00%)	0 / 13 (0.00%)	8 / 93 (8.60%)
occurrences all number	0	0	13
Hypercalcaemia
subjects affected / exposed	2 / 31 (6.45%)	0 / 13 (0.00%)	6 / 93 (6.45%)
occurrences all number	3	0	6
Hypoalbuminaemia
subjects affected / exposed	1 / 31 (3.23%)	0 / 13 (0.00%)	6 / 93 (6.45%)
occurrences all number	1	0	7

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Were there any global substantial amendments to the protocol? Yes

21 May 2013

- The enrolled first-line participants could not continue treatment with atezolizumab beyond PD per RECIST v1.1; - The exclusion criterion for hepatitis B was clarified to exclude participants with active hepatitis B but permit enrollment to participants with a past hepatitis B virus infection or resolved hepatitis B virus infection; - The total number of participants to be enrolled was increased to allow for a total of 75 participants in the 2L+ arm and 130 participants in the study; - Statistical considerations section was clarified that there was no plan to perform a formal statistical comparison of the response rates between the three arms; - Minor changes were made to improve clarity and consistency.

16 Aug 2013

- Clarifications made to the inclusion criterion unique to 2L+ Brain Metastases Participants arm specifying that brain metastases had to be treated and asymptomatic at screening for participants to be eligible; - A new exclusion criterion for participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation was added. Clarifications were made on exclusion criteria for participants with known hypersensitivity with Chinese hamster ovary cell products, positive human immunovirus test, and past or resolved hepatitis B virus infection; - Clarifications were made to assessment of vital signs, observation time for infusions, and reporting of delayed post-infusion symptoms; - Guidelines were added to specify the importance of continued monitoring of participants for signs or symptoms of new or worsening brain involvement; - The window for prior treatment with immunostimulatory agents was adjusted; - Additional minor changes were made to improve clarity and consistency.

21 May 2014

- Updated the protocol with more recent efficacy and safety information for atezolizumab; - The duration of treatment was modified to allow participants to be treated until no longer experiencing clinical benefit; accordingly the 1-year initial treatment, follow-up, and re-treatment periods were not applicable; - The frequency of tumor assessments was reduced after 1 year of treatment and the safety follow-up period was changed from 90 to 30 days; - The clinical safety experience and dose modification guidelines for duration of treatment suspension and treatment of specific toxicities were updated; - Additional minor changes were made to improve clarity and consistency.

19 Sep 2014

- The safety follow-up was reverted to original 90 days from 30 days implemented in the protocol amendment 3 (dated 21 May 2014) to allow further evaluation of safety after treatment discontinuation and to maintain consistency within the study across all sites; - The clinical experience section of the protocol was updated to align with the Investigator's Brochure and to maintain consistency across active atezolizumab protocols with respect to description of risks and adverse event management guidelines; - Additional minor changes were made to improve clarity and consistency.

04 Nov 2015

- The Atezolizumab Investigator’s Brochure (IB), Version 7 outlined the defined guidelines for the management of immune-mediated toxicity. Given this, the management of gastrointestinal dermatologic, endocrine, pulmonary toxicity, hepatotoxicity, potential pancreatic or eye toxicity and other immune-mediated adverse events were removed from the protocol and reference was made to the IB; - Systemic immune activation (SIA) was identified as a potential risk of atezolizumab when given in combination with other immunomodulating agents. The management recommendations regarding early identification and management of SIA were added.

31 Oct 2016

- If the Sponsor decided to terminate Study GO28625, patients were offered the option of enrollment in an extension study in order to allow them continued access to atezolizumab treatment. The definition of the End of Study and post-trial access to atezolizumab were revised to reflect this information; - On the basis of updated clinical data regarding the atezolizumab half-life of 27 days, the following changes were implemented: The period during which female patients must remain abstinent or use contraception and the length of follow up of pregnancy reporting, were revised to 5 months after the last dose of study drug; and the period during which patients must agree not to receive live, attenuated vaccine was revised from 90 days to 5 months after the last dose of study drug; - The contraception requirements for male patients and the pregnancy reporting requirements for female partners of male patients were removed to align with the updated safety information for atezolizumab; - The 1-hour post-dose vital sign measurement was removed for infusions that occurred subsequent to the initial infusion. Vital signs for these infusions were to occur within 60 minutes before the infusion and during the infusion if clinically indicated; - Traditional herbal medicines were removed from prohibited therapies, and language was added to state that concomitant use of herbal therapies is not recommended because the pharmacokinetics, safety profile, and potential drug-drug interactions were generally unknown. Use of herbal therapies for patients in the study was allowed only at the discretion of the investigator, provided that there were no known interactions with any study treatment.

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.

Not specified.

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Clinical trials

Clinical Trial Results: A Phase II, Multicenter, Single-Arm Study of Atezolizumab (MPDL3280A) in Patients with PD-L1Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)

Primary: Percentage of Participants with Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)

Secondary: Percentage of Participants with Objective Response According to RECIST Version 1.1 (v1.1)

Secondary: Percentage of Participants with Objective Response According to RECIST Version 1.1 (v1.1)

Secondary: Duration of Objective Response According to RECIST v1.1

Secondary: Duration of Objective Response According to RECIST v1.1

Secondary: Percentage of Participants with 6-Month Duration of Objective Response

Secondary: Percentage of Participants with 6-Month Duration of Objective Response

Secondary: Percentage of Participants with Disease Progression or Death According to RECIST v1.1

Secondary: Percentage of Participants with Disease Progression or Death According to RECIST v1.1

Secondary: Progression-Free Survival (PFS) According to RECIST v1.1

Secondary: Progression-Free Survival (PFS) According to RECIST v1.1

Secondary: Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1

Secondary: Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to RECIST v1.1

Secondary: Percentage of Participants with Disease Progression or Death According to Modified RECIST

Secondary: Percentage of Participants with Disease Progression or Death According to Modified RECIST

Secondary: PFS According to Modified RECIST

Secondary: PFS According to Modified RECIST

Secondary: Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to Modified RECIST

Secondary: Percentage of Participants with PFS at Month 6, Month 12 and Month 30 According to Modified RECIST

Secondary: Percentage of Participants with Death

Secondary: Percentage of Participants with Death

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Maximum Plasma Concentration (Cmax) for Atezolizumab

Secondary: Maximum Plasma Concentration (Cmax) for Atezolizumab

Secondary: Minimum Plasma Concentration (Cmin) for Atezolizumab

Secondary: Minimum Plasma Concentration (Cmin) for Atezolizumab

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Multicenter, Single-Arm Study of Atezolizumab (MPDL3280A) in Patients with PD-L1Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer.