Trial Outcomes & Findings for A Study of Atezolizumab in Participants With Programmed Death - Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NCT NCT02031458)

NCT ID: NCT02031458

Last Updated: 2020-01-06

Results Overview

ORR was the percentage of participants whose confirmed best overall response was either a Partial Response (PR) or a Complete Response (CR) based upon the IRF assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm); PR:greater than (\>) or equal to (=) 30 percent (%) decrease from baseline in sum of diameters of target lesions, non-progressive disease (PD) non-target lesions and no new lesions. Results were reported by line of therapy and programmed death-ligand 1 (PD-L1) Expression Subgroup (tumor cell \[TC\]3 \[TC3\] or tumor-infiltrating immune cell \[IC\] 3 \[IC3\], TC3 or IC2/3, TC2/3 or IC2/3).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

667 participants

Primary outcome timeframe

Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)

Results posted on

2020-01-06

Participant Flow

Since the primary cut-off date May 8, 2015 one participant in Cohort 1 has moved to Cohort 2 and one participant in Cohort 3 was moved to Cohort 2.

Screening was performed from Day -28 to Day -1.

Participant milestones

Participant milestones
Measure	Cohort 1: First Line Atezolizumab Participants received 1200 milligrams (mg) atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by intravenous (IV) infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in Eastern Cooperative Oncology Group (ECOG) performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.
May 8, 2015 to January 11, 2019 STARTED	138	269	252
May 8, 2015 to January 11, 2019 COMPLETED	0	0	0
May 8, 2015 to January 11, 2019 NOT COMPLETED	138	269	252
Baseline to May 8, 2015 STARTED	139	267	253
Baseline to May 8, 2015 COMPLETED	0	0	0
Baseline to May 8, 2015 NOT COMPLETED	139	267	253

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: First Line Atezolizumab Participants received 1200 milligrams (mg) atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by intravenous (IV) infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in Eastern Cooperative Oncology Group (ECOG) performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.
May 8, 2015 to January 11, 2019 Death	89	193	198
May 8, 2015 to January 11, 2019 Lost to Follow-up	2	5	8
May 8, 2015 to January 11, 2019 Switched over to commercial Atezolizumab	1	6	6
May 8, 2015 to January 11, 2019 Physician Decision	2	3	3
May 8, 2015 to January 11, 2019 Protocol Violation	7	4	0
May 8, 2015 to January 11, 2019 Study Terminated by Sponsor	24	42	23
May 8, 2015 to January 11, 2019 Withdrawal by Subject	13	16	14
Baseline to May 8, 2015 Death	36	87	100
Baseline to May 8, 2015 Protocol Violation	7	4	0
Baseline to May 8, 2015 Physician Decision	0	1	0
Baseline to May 8, 2015 Unknown Reason	0	1	2
Baseline to May 8, 2015 Withdrawal by Subject	6	9	3
Baseline to May 8, 2015 On Survival Follow-Up	46	83	73
Baseline to May 8, 2015 On Treatment	43	81	73
Baseline to May 8, 2015 Lost to Follow-up	1	1	2

Baseline Characteristics

A Study of Atezolizumab in Participants With Programmed Death - Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: First Line Atezolizumab n=138 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=269 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=252 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Total n=659 Participants Total of all reporting groups
Age, Continuous	66.8 years STANDARD_DEVIATION 10.3 • n=5 Participants	62.4 years STANDARD_DEVIATION 10.2 • n=7 Participants	63.6 years STANDARD_DEVIATION 9.4 • n=5 Participants	63.7 years STANDARD_DEVIATION 10.0 • n=4 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	104 Participants n=7 Participants	100 Participants n=5 Participants	272 Participants n=4 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	165 Participants n=7 Participants	152 Participants n=5 Participants	387 Participants n=4 Participants

PRIMARY outcome

Timeframe: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)

Population: Efficacy evaluable population; Number (n) equals (=) number of participants analyzed within the specified group.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants Achieving Objective Response (ORR) Per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 as Assessed by Independent Review Facility (IRF) TC2/3 or IC2/3 Responders	19.4 percentage of participants Interval 13.2 to 27.0	17.2 percentage of participants Interval 12.9 to 22.3	17.4 percentage of participants Interval 12.9 to 22.6	17.3 percentage of participants Interval 14.2 to 20.8
Percentage of Participants Achieving Objective Response (ORR) Per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 as Assessed by Independent Review Facility (IRF) TC3 or IC3 Responders	26.2 percentage of participants Interval 16.0 to 38.5	23.8 percentage of participants Interval 16.5 to 32.3	27.0 percentage of participants Interval 19.1 to 36.0	25.35 percentage of participants Interval 19.9 to 31.4
Percentage of Participants Achieving Objective Response (ORR) Per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 as Assessed by Independent Review Facility (IRF) TC3 or IC2/3 Responders	21.1 percentage of participants Interval 14.3 to 29.4	17.4 percentage of participants Interval 12.9 to 22.7	18.2 percentage of participants Interval 13.5 to 23.8	17.8 percentage of participants Interval 14.5 to 21.5

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

ORR was the percentage of participants whose confirmed best overall response was either a PR or a CR based upon the Investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10mm; PR: \> or = 30 % decrease from baseline in sum of diameters of target lesions, non-PD non-target lesions and no new lesions. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3).

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) TC3 or IC2/3 Responders	24.4 percentage of participants Interval 17.1 to 33.0	19.4 percentage of participants Interval 14.7 to 24.9	19.1 percentage of participants Interval 14.3 to 24.7	19.3 percentage of participants Interval 15.8 to 23.1
Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) TC2/3 or IC2/3 Responders (n= 139, 267, 253, 520)	22.3 percentage of participants Interval 15.7 to 30.1	18.7 percentage of participants Interval 14.2 to 23.9	18.2 percentage of participants Interval 13.6 to 23.5	18.5 percentage of participants Interval 15.2 to 22.1
Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV) TC3 or IC3 Responders	30.8 percentage of participants Interval 19.9 to 43.5	24.6 percentage of participants Interval 17.3 to 33.2	28.7 percentage of participants Interval 20.7 to 37.9	26.6 percentage of participants Interval 21.1 to 32.7

SECONDARY outcome

Population: Efficacy evaluable population; n= number of participants analyzed within the specified group.

ORR was the percentage of participants whose confirmed best overall response was either a PR or a CR based upon the Investigator assessment per modified RECIST. CR: disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10mm; PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3).

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV TC3 or IC2/3 Responders	16.3 percentage of participants Interval 10.2 to 24.0	21.9 percentage of participants Interval 16.9 to 27.5	20.8 percentage of participants Interval 15.8 to 26.5	21.3 percentage of participants Interval 17.8 to 25.3
Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV TC2/3 or IC2/3 Responders	15.8 percentage of participants Interval 10.2 to 23.0	21.0 percentage of participants Interval 16.3 to 26.4	19.8 percentage of participants Interval 15.0 to 25.2	20.4 percentage of participants Interval 17.0 to 24.1
Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV TC3 or IC3 Responders	20.0 percentage of participants Interval 11.1 to 31.8	27.0 percentage of participants Interval 19.4 to 35.8	30.4 percentage of participants Interval 22.2 to 39.7	28.7 percentage of participants Interval 23.0 to 34.9

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group. Number of participants analyzed = overall number of participants who were evaluable for this outcome.

DOR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and the first date that PD or death is documented, whichever occurs first as measured by RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10mm; PR: \> or = 30 % decrease from baseline in sum of diameters of target lesions, non-PD non-target lesions and no new lesions; PD: one or more of the following: at least 20% increase from nadir in sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. DOR was assessed by Kaplan-Meier estimates. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3).

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=27 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=46 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=44 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=90 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 TC3 or IC3 DOR	NA months Interval 5.8 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 4.9 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	7.2 months Interval 5.6 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	7.2 months Interval 5.7 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 TC3 or IC2/3 DOR	8.5 months Interval 5.6 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 6.9 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 5.7 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 6.9 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
Duration of Response (DOR) Assessed by IRF Per RECIST v1.1 TC2/3 or IC2/3 DOR	8.5 months Interval 5.6 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 6.9 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 5.7 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 6.9 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

DOR is interval between date of the first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10mm; PR: \> or = 30 % decrease from baseline in sum of diameters of target lesions, non-PD non-target lesions and no new lesions; PD: one or more of the following: at least 20% increase from nadir in sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. DOR was assessed by Kaplan-Meier estimates. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3).

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=81 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=128 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=124 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=252 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
DOR as Assessed by INV Per RECIST v1.1 TC3 or IC3 DOR	8.5 months Interval 5.6 to 8.5	NA months Interval 8.1 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.4 months Interval 6.4 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 7.4 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
DOR as Assessed by INV Per RECIST v1.1 TC3 or IC2/3 DOR	8.5 months Interval 8.5 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.3 months Interval 7.0 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 8.3 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
DOR as Assessed by INV Per RECIST v1.1 TC2/3 or IC2/3 DOR	NA months Interval 8.5 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	8.3 months Interval 7.0 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 8.3 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

DOR is the interval between the date of the first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and the first date that PD or death is documented, whichever occurs first as measured by modified RECIST. CR: disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10mm; PR: at least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR; PD: one or more of the following: at least 20% increase from nadir in the sum of diameters of existing and/or new target lesions (with an absolute increase of at least 5mm). DOR was assessed by Kaplan-Meier estimates. Results were reported by line of therapy (reporting arms) and PD-L1 Expression Subgroup (TC3 or IC3, TC3 or IC2/3, TC2/3 or IC2/3).

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=55 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=143 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=134 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=277 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
DOR as Assessed by INV Per Modified RECIST TC3 or IC3 DOR	NA months Interval 4.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 8.1 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 7.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 8.1 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
DOR as Assessed by INV Per Modified RECIST TC3 or IC2/3 DOR	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 7.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
DOR as Assessed by INV Per Modified RECIST TC2/3 or IC2/3 DOR	NA months Interval 4.5 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 7.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

PFS is the interval between the first dose of atezolizumab and date of disease progression or death due to any cause, whichever occurred first as measured by RECIST v1.1. PD is defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. PFS was assessed by Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 TC3 or IC3 PFS	5.5 months Interval 2.7 to 8.3	4.1 months Interval 1.8 to 5.5	4.2 months Interval 2.8 to 5.6	4.1 months Interval 2.8 to 5.4
Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 TC3 or IC2/3 PFS	5.6 months Interval 3.3 to 8.3	2.8 months Interval 1.5 to 4.0	2.8 months Interval 2.7 to 4.0	2.8 months Interval 2.7 to 3.0
Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1 TC2/3 or IC2/3 PFS	5.5 months Interval 3.0 to 6.9	2.8 months Interval 1.5 to 3.5	2.8 months Interval 2.7 to 3.7	2.8 months Interval 2.7 to 2.9

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

PFS is the interval between the first dose of atezolizumab and date of disease progression or death due to any cause, whichever occurred first as measured by RECIST v1.1. PD: one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions. PFS was assessed by Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
PFS as Assessed by INV Per RECIST v1.1 TC3 or IC3 PFS	7.1 months Interval 4.9 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	4.1 months Interval 2.7 to 6.5	4.2 months Interval 3.0 to 6.2	4.2 months Interval 2.9 to 5.6
PFS as Assessed by INV Per RECIST v1.1 TC3 or IC2/3 PFS	7.6 months Interval 5.9 to 9.9	3.0 months Interval 2.7 to 4.2	3.5 months Interval 2.8 to 4.2	3.2 months Interval 2.8 to 4.1
PFS as Assessed by INV Per RECIST v1.1 TC2/3 or IC2/3 PFS	7.1 months Interval 5.6 to 8.4	2.8 months Interval 2.6 to 4.1	3.0 months Interval 2.8 to 4.1	3.0 months Interval 2.8 to 4.1

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

PFS is the interval between the first dose of atezolizumab and date of disease progression or death due to any cause, whichever occurred first as measured by modified RECIST. PD: at least 20% increase from nadir in the sum of diameters of new and/or existing target lesions (with an absolute increase of at least 5mm). PFS was assessed by Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
PFS as Assessed by INV Per Modified RECIST TC3 or IC3 PFS	7.1 months Interval 4.7 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	5.7 months Interval 4.1 to 8.4	6.3 months Interval 4.1 to 8.1	5.8 months Interval 4.3 to 7.1
PFS as Assessed by INV Per Modified RECIST TC3 or IC2/3 PFS	7.9 months Interval 5.7 to 10.0	4.5 months Interval 4.0 to 6.0	4.9 months Interval 4.1 to 6.8	4.6 months Interval 4.1 to 5.7
PFS as Assessed by INV Per Modified RECIST TC2/3 or IC2/3 PFS	7.6 months Interval 5.6 to 9.9	4.2 months Interval 3.9 to 5.7	4.6 months Interval 4.1 to 6.3	4.4 months Interval 4.1 to 5.5

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Overall Survival : Percentage of Participants Without Event (Death) TC3 or IC3	70.8 percentage of participants	70.5 percentage of participants	67.0 percentage of participants	68.8 percentage of participants
Overall Survival : Percentage of Participants Without Event (Death) TC2/3 or IC2/3	74.1 percentage of participants	67.4 percentage of participants	60.5 percentage of participants	64.0 percentage of participants
Overall Survival : Percentage of Participants Without Event (Death) TC3 or IC2/3	75.6 percentage of participants	69.2 percentage of participants	60.6 percentage of participants	65.0 percentage of participants

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

Overall survival is measured as interval between the first dose of atezolizumab and date of death from any cause.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Overall Survival : Median Time to Event (Death) TC3 or IC2/3	14.0 months Interval 14.0 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 12.1 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 8.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 12.1 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
Overall Survival : Median Time to Event (Death) TC3 or IC3	NA months Interval 10.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 10.6 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 12.1 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
Overall Survival : Median Time to Event (Death) TC2/3 or IC2/3	14.0 months Interval 14.0 to Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 11.2 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 8.4 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.	NA months Interval 11.2 to Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

Timeframe: Month 6

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants Without an Event (Death) at 6 Months TC3 or IC2/3	83.9 percentage of participants Interval 77.2 to 90.5	78.1 percentage of participants Interval 72.8 to 83.4	71.0 percentage of participants Interval 65.2 to 76.9	74.6 percentage of participants Interval 70.6 to 78.5
Percentage of Participants Without an Event (Death) at 6 Months TC2/3 or IC2/3	81.7 percentage of participants Interval 75.1 to 88.4	76.2 percentage of participants Interval 71.0 to 81.5	70.5 percentage of participants Interval 64.9 to 76.2	73.4 percentage of participants Interval 69.5 to 77.3
Percentage of Participants Without an Event (Death) at 6 Months TC3 or IC3	79.2 percentage of participants Interval 69.1 to 89.3	79.7 percentage of participants Interval 72.5 to 87.0	75.1 percentage of participants Interval 67.1 to 83.1	77.4 percentage of participants Interval 72.0 to 82.8

SECONDARY outcome

Timeframe: Month 12

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants Without an Event (Death) at 12 Months TC3 or IC2/3	67.1 percentage of participants Interval 55.7 to 78.4	59.3 percentage of participants Interval 50.5 to 68.1	54.9 percentage of participants Interval 47.7 to 62.2	56.5 percentage of participants Interval 50.6 to 62.5
Percentage of Participants Without an Event (Death) at 12 Months TC2/3 or IC2/3	65.0 percentage of participants Interval 54.0 to 76.1	57.2 percentage of participants Interval 48.6 to 65.7	54.4 percentage of participants Interval 47.3 to 61.5	55.3 percentage of participants Interval 49.5 to 61.1
Percentage of Participants Without an Event (Death) at 12 Months TC3 or IC3	58.6 percentage of participants Interval 40.7 to 76.5	61.5 percentage of participants Interval 49.0 to 74.0	62.6 percentage of participants Interval 52.8 to 72.5	61.3 percentage of participants Interval 52.7 to 69.8

SECONDARY outcome

Timeframe: Month 6

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

PD is defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5mm), appearance of new lesions, and/or unequivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
PFS: Percentage of Participants Alive and Progression Free at 6 Months TC2/3 or IC2/3	56.4 percentage of participants Interval 47.8 to 65.1	34.8 percentage of participants Interval 29.0 to 40.7	34.7 percentage of participants Interval 28.7 to 40.6	34.8 percentage of participants Interval 30.6 to 38.9
PFS: Percentage of Participants Alive and Progression Free at 6 Months TC3 or IC3	57.4 percentage of participants Interval 44.7 to 70.1	41.3 percentage of participants Interval 32.3 to 50.4	42.1 percentage of participants Interval 33.1 to 51.2	41.8 percentage of participants Interval 35.4 to 48.2
PFS: Percentage of Participants Alive and Progression Free at 6 Months TC3 or IC2/3	58.6 percentage of participants Interval 49.5 to 67.8	36.1 percentage of participants Interval 29.9 to 42.2	35.8 percentage of participants Interval 29.6 to 41.9	35.9 percentage of participants Interval 31.6 to 40.3

SECONDARY outcome

Timeframe: Month 12

Population: Efficacy evaluable population; n = number of participants analyzed within the specified group.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
PFS: Percentage of Participants Alive and Progression Free at 12 Months TC3 or IC3	33.1 percentage of participants Interval 14.9 to 51.3	27.8 percentage of participants Interval 17.6 to 37.9	16.1 percentage of participants Interval 3.8 to 28.5	23.1 percentage of participants Interval 15.4 to 30.8
PFS: Percentage of Participants Alive and Progression Free at 12 Months TC3 or IC2/3	29.0 percentage of participants Interval 13.1 to 45.0	22.7 percentage of participants Interval 16.1 to 29.3	15.1 percentage of participants Interval 8.3 to 21.8	19.1 percentage of participants Interval 14.4 to 23.8
PFS: Percentage of Participants Alive and Progression Free at 12 Months TC2/3 or IC2/3	26.9 percentage of participants Interval 12.1 to 41.7	21.8 percentage of participants Interval 15.5 to 28.1	14.7 percentage of participants Interval 8.1 to 21.3	18.5 percentage of participants Interval 14.0 to 23.1

SECONDARY outcome

Population: Efficacy evaluable population

TIR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by RECIST v1.1. For responders, TIR was the same as DOR; for non-responders, TIR was considered as an event and defined as the date of first treatment plus one day. TIR was assessed by Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Time in Response (TIR) as Assessed by INV Per RECIST v1.1	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

Population: Efficacy evaluable population

TIR is interval between date of first occurrence of a CR or PR that is subsequently confirmed (whichever status is recorded first) and first date that PD or death is documented, whichever occurs first as measured by modified RECIST. For responders, TIR was the same as DOR; for non-responders, TIR was considered as an event and defined as the date of first treatment plus one day. TIR was assessed by Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
TIR as Assessed by INV Per Modified RECIST	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

Population: Efficacy evaluable population

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
TIR as Assessed by IRF Per RECIST v1.1	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.	0.033 months Median reported is the censored value, confidence interval not estimable by Brookmeyer and Crowley method due to insufficient observed events.

SECONDARY outcome

Timeframe: Pre-dose (hour 0) and 0.5 hours post dose on Cycle 1 Day 1 (Cycle length = 21days), Cycle 1 Days 2, 4, 8, 15, and 21, Cycle 2 Day 21, Cycle 3 Day 21, Cycle 7 Day 21

Population: Pharmacokinetic evaluable population; n = number of participants analyzed for the specified time point.

Serum concentrations were determined for all participants after administration of atezolizumab up to Cycle 8. Time (T) = time from first dose in days.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=646 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Atezolizumab Serum Concentrations Cycle 1 Day 1 T=0	0.285 micrograms per milliliter (μg/mL) Standard Deviation 4.35	—	—	—
Atezolizumab Serum Concentrations Cycle 1 Day 1 T=0.021	429.0 micrograms per milliliter (μg/mL) Standard Deviation 218	—	—	—
Atezolizumab Serum Concentrations Cycle 1 Day 2 T=1	299.0 micrograms per milliliter (μg/mL) Standard Deviation 65.3	—	—	—
Atezolizumab Serum Concentrations Cycle 1 Day 4 T=3	220.0 micrograms per milliliter (μg/mL) Standard Deviation 48.4	—	—	—
Atezolizumab Serum Concentrations Cycle 1 Day 8 T=7	155.0 micrograms per milliliter (μg/mL) Standard Deviation 35.4	—	—	—
Atezolizumab Serum Concentrations Cycle 1 Day 15 T=14	106.0 micrograms per milliliter (μg/mL) Standard Deviation 32.1	—	—	—
Atezolizumab Serum Concentrations Cycle 1 Day 21 T=21	87.8 micrograms per milliliter (μg/mL) Standard Deviation 41.7	—	—	—
Atezolizumab Serum Concentrations Cycle 2 Day 21 T=42	134.0 micrograms per milliliter (μg/mL) Standard Deviation 57.2	—	—	—
Atezolizumab Serum Concentrations Cycle 3 Day 21 T=63	163.0 micrograms per milliliter (μg/mL) Standard Deviation 70.7	—	—	—
Atezolizumab Serum Concentrations Cycle 7 Day 21 T=147	212.0 micrograms per milliliter (μg/mL) Standard Deviation 88.5	—	—	—

SECONDARY outcome

Timeframe: Baseline, post-baseline (up to 16 months)

Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point. Number of participants analyzed = number participants who were evaluable for this outcome.

Anti-therapeutic antibodies is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=135 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=257 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=247 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=504 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status Baseline	7.4 percentage of participants	3.5 percentage of participants	6.1 percentage of participants	4.8 percentage of participants
Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status Post-Baseline	45.1 percentage of participants	36.0 percentage of participants	37.4 percentage of participants	36.7 percentage of participants

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point.

PD was defined as one or more of the following: at least 20% increase from nadir in the sum of diameters of target lesions (with an absolute increase of at least 5 mm), appearance of new lesions, and/or unequivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 TC3 or IC3	58.5 percentage of participants	68.0 percentage of participants	73.0 percentage of participants	70.5 percentage of participants
Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 TC3 or IC2/3	61.8 percentage of participants	73.7 percentage of participants	79.2 percentage of participants	76.4 percentage of participants
Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1 TC2/3 or IC2/3	63.3 percentage of participants	75.3 percentage of participants	79.1 percentage of participants	77.1 percentage of participants

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point.

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 TC3 or IC3	50.8 percentage of participants	63.1 percentage of participants	68.7 percentage of participants	65.8 percentage of participants
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 TC3 or IC2/3	50.4 percentage of participants	68.8 percentage of participants	74.6 percentage of participants	71.6 percentage of participants
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1 TC2/3 or IC2/3	52.5 percentage of participants	70.0 percentage of participants	74.7 percentage of participants	72.3 percentage of participants

SECONDARY outcome

Population: Efficacy evaluable population; n = number of participants analyzed at the specified time point.

PD was defined as at least 20% increase from nadir in the sum of diameters of new and/or existing target lesions (with an absolute increase of at least 5 mm).

Outcome measures

Outcome measures
Measure	Cohort 1: First Line Atezolizumab n=139 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21 day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants in this cohort received no prior chemotherapy in locally advanced or metastatic setting.	Cohort 2: Second Line Atezolizumab n=267 Participants Participants received 1200 mg atezolizumab every 3 weeks (Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: evidence of clinical benefit as assessed by the investigator; absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy in locally advanced or metastatic setting.	Cohort 3: Third Line and Beyond Atezolizumab n=253 Participants Participants received 1200 mg atezolizumab every 3 weeks ( Day 1 of 21-day cycle) administered by IV infusion until intolerable toxicity, disease progression or death. Participants were permitted to continue treatment after progressive disease, if the following criteria were met: absence of symptoms and signs indicating unequivocal progression of disease; no decline in ECOG performance status; absence of tumor growth at critical anatomical sites that cannot be managed by protocol-allowed medical interventions; evidence of clinical benefit as assessed by the investigator. Participants in this cohort progressed during or after prior platinum-based chemotherapy and at least one additional therapy in locally advanced or metastatic setting.	Cohorts 2 + 3 n=520 Participants This sub-group included participants from cohorts 2 and 3. All participants who were treated and had evaluable pharmacokinetic samples were included in this group.
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 TC3 or IC3	36.9 percentage of participants	56.6 percentage of participants	60.0 percentage of participants	58.2 percentage of participants
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 TC3 or IC2/3	38.2 percentage of participants	61.5 percentage of participants	66.1 percentage of participants	63.8 percentage of participants
Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1 TC2/3 or IC2/3	39.6 percentage of participants	62.9 percentage of participants	66.4 percentage of participants	64.6 percentage of participants

Adverse Events

Cohort 1: First Line Atezolizumab

Serious events: 47 serious events

Other events: 116 other events

Deaths: 89 deaths

Cohort 2: Second Line Atezolizumab

Serious events: 117 serious events

Other events: 229 other events

Deaths: 193 deaths

Cohort 3: Third Line and Beyond Atezolizumab

Serious events: 113 serious events

Other events: 229 other events

Deaths: 198 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER