Trial Outcomes & Findings for A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer (NCT NCT04619797)

NCT ID: NCT04619797

Last Updated: 2026-06-03

Results Overview

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. Kaplan-Meier (KM) methodology was used to estimate the median PFS.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

542 participants

Primary outcome timeframe

From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Results posted on

2026-06-03

Participant Flow

A total of 542 participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) took part in the study at 129 investigative sites across 21 countries from 15 December 2020 to 20 November 2025.

Participants were randomized in a 1:1 ratio to receive either tiragolumab + atezolizumab + chemotherapy or placebo + pembrolizumab + chemotherapy. The study is considered "Completed" because all the pre-planned study activities and analyses have been performed.

Participant milestones

Participant milestones
Measure	Placebo + Pembrolizumab + Chemotherapy Participants received pembrolizumab at a fixed dose 200 milligrams (mg), placebo, pemetrexed, 500 milligram per square meter (mg/m\^2), and either carboplatin, area under the curve (AUC) of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until disease progression (PD), loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Overall Study STARTED	273	269
Overall Study Safety-evaluable Set	272	267
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	273	269

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Pembrolizumab + Chemotherapy Participants received pembrolizumab at a fixed dose 200 milligrams (mg), placebo, pemetrexed, 500 milligram per square meter (mg/m\^2), and either carboplatin, area under the curve (AUC) of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until disease progression (PD), loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Overall Study Withdrawal by Subject	20	15
Overall Study Study Ended by Sponsor	137	108
Overall Study Protocol Deviation	0	1
Overall Study Lost to Follow-up	3	0
Overall Study Death	113	145

Baseline Characteristics

A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Total n=542 Participants Total of all reporting groups
Age, Continuous	63.4 years STANDARD_DEVIATION 9.3 • n=20 Participants	63.9 years STANDARD_DEVIATION 9.4 • n=20 Participants	63.6 years STANDARD_DEVIATION 9.3 • n=40 Participants
Sex: Female, Male Female	104 Participants n=20 Participants	85 Participants n=20 Participants	189 Participants n=40 Participants
Sex: Female, Male Male	169 Participants n=20 Participants	184 Participants n=20 Participants	353 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	39 Participants n=20 Participants	28 Participants n=20 Participants	67 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	229 Participants n=20 Participants	237 Participants n=20 Participants	466 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=20 Participants	4 Participants n=20 Participants	9 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	12 Participants n=20 Participants	10 Participants n=20 Participants	22 Participants n=40 Participants
Race (NIH/OMB) Asian	89 Participants n=20 Participants	87 Participants n=20 Participants	176 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=20 Participants	1 Participants n=20 Participants	4 Participants n=40 Participants
Race (NIH/OMB) Black or African American	2 Participants n=20 Participants	4 Participants n=20 Participants	6 Participants n=40 Participants
Race (NIH/OMB) White	163 Participants n=20 Participants	165 Participants n=20 Participants	328 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=20 Participants	2 Participants n=20 Participants	6 Participants n=40 Participants

PRIMARY outcome

Timeframe: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Progression-free Survival (PFS) as Determined by the Investigator	9.89 months Interval 8.71 to 11.89	8.31 months Interval 7.13 to 9.59

PRIMARY outcome

Timeframe: From randomization to death from any cause (up to approximately 40 months)

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Overall Survival (OS)	23.10 months Interval 20.73 to 32.95	18.89 months Interval 15.24 to 23.79

SECONDARY outcome

Timeframe: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Population: Per protocol, centralized, blinded review of responses and endpoints by IRF may be conducted at the sponsor's discretion. Since protocol was amended to stop the submission of primary imaging data used for tumor assessments to IRF, no data was collected for this endpoint.

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1 criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Population: PD-L1 TPS/TC \>=1% subgroup population included all FAS participants with PD-L1 expression at TPS/TC \>=1% , as determined by central testing with investigational Ventana PD-L1 (SP263) assay. FAS included all randomized participants whether or not the participants received the assigned treatment.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=152 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=162 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=1%	11.96 months Interval 9.72 to 16.59	9.82 months Interval 8.25 to 12.85

SECONDARY outcome

Timeframe: From randomization to first occurrence of PD or death from any cause (up to approximately 40 months)

Population: PD-L1 TPS/TC \>=50% subgroup population included all FAS participants with PD-L1 expression at TPS/TC\>=50%, as determined by central testing with investigational Ventana PD-L1 (SP263) assay. FAS included all randomized participants whether or not the participants received the assigned treatment.

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions. KM methodology was used to estimate the median PFS.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=78 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=84 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=50%	14.09 months Interval 10.94 to 33.74	11.76 months Interval 9.46 to 15.21

SECONDARY outcome

Timeframe: From randomization to death from any cause (up to approximately 40 months)

Population: PD-L1 TPS/TC \>=1% subgroup population included all FAS participants with PD-L1 expression at TPS/TC \>=1%, as determined by central testing with investigational Ventana PD-L1 (SP263) assay. FAS included all randomized participants whether or not the participants received the assigned treatment.

OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=152 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=162 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
OS in Participants With PD-L1 Expression at TPS/TC >=1%	33.58 months Interval 22.64 to The upper limit of the 95% confidence interval (CI) was not estimable due to insufficient number of participants with events.	20.70 months Interval 16.89 to 32.92

SECONDARY outcome

Timeframe: From randomization to death from any cause (up to approximately 40 months)

OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=78 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=84 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
OS in Participants With PD-L1 Expression at TPS/TC >= 50%	33.58 months Interval 22.64 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	23.79 months Interval 17.28 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: At Month 6 and Month 12

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

PFS at 6 months and 12 months was defined as the percentage of participants who have not experienced PD as determined by the investigator according to RECIST v1.1 or death from any cause at 6 months and at 12 months, respectively. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
PFS Rate at Month 6 and Month 12 Month 6	68.52 percentage of participants Interval 62.94 to 74.1	61.12 percentage of participants Interval 55.25 to 66.99
PFS Rate at Month 6 and Month 12 Month 12	42.79 percentage of participants Interval 36.42 to 49.15	34.26 percentage of participants Interval 28.21 to 40.31

SECONDARY outcome

Timeframe: At Month 12 and Month 24

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

OS rate at 12 months and 24 months was defined as the percentage of participants who have not experienced death from any cause at 12 and 24 months, respectively.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
OS Rate at Month 12 and Month 24 Month 12	72.34 percentage of participants Interval 66.76 to 77.92	63.38 percentage of participants Interval 57.34 to 69.43
OS Rate at Month 12 and Month 24 Month 24	47.95 percentage of participants Interval 39.14 to 56.77	41.90 percentage of participants Interval 33.98 to 49.82

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment. Overall number analyzed is the number of participants with data available for analysis.

DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Complete response (CR) was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Partial response (PR) was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. KM methodology was used to estimate the median DOR.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=154 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=135 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Duration of Response (DOR)	11.1 months Interval 9.5 to 18.9	9.4 months Interval 8.2 to 11.7

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

ORR was defined as a percentage of participants with a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=272 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Objective Response Rate (ORR)	56.6 percentage of participants Interval 50.49 to 62.55	50.2 percentage of participants Interval 44.07 to 56.3

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

EORTC QLQ-C30=self-reported measure, with 30 questions assessing 5 aspects of subjects functioning (physical, emotional, role, cognitive \& social), 3 symptom scales (fatigue, nausea \& vomiting, \& pain), global health status (GHS) \& Quality of Life (QoL), \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties) within the previous week. Functioning \& symptoms items were scored on a 4-point scale: 1=not at all to 4=very much. Scores were linearly transformed to a range of 0 to 100, with higher scores reflecting better functioning. TTCD was defined time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration was defined as score decrease of ≥10 from baseline in PF scale score that were held for at least two consecutive assessments or an initial ≥10 decrease from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning (PF) as Measured by European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC-QLQ-C30)	30.36 months Interval 25.33 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	20.76 months Interval 11.79 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

EORTC QLQ-C30=self-reported measure, with 30 questions assessing 5 aspects of subjects functioning (physical, emotional, role, cognitive \& social), 3 symptom scales (fatigue, nausea \& vomiting, \& pain), global health status (GHS) \& Quality of Life (QoL), \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties) within the previous week . GHS and QoL items were scored on a 7-point scale (1=very poor 7=excellent). Scores were linearly transformed to a range of 0 to 100, with higher scores reflecting better GHS/QoL. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration was defined as score decrease of ≥10 from baseline in GHS/QoL scale score that were held for at least two consecutive assessments or an initial ≥10 decrease from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
TTCD in Participant-Reported Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30	NA months Interval 14.55 to The median and upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	NA months Interval 17.05 to The median and upper limit of the 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

The EORTC QLQ-LC13 is comprised of 13 lung cancer-specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Symptoms were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of dyspnoea. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
TTCD in Participant-Reported Dyspnoea as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13)	16.99 months Interval 10.32 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	23.52 months Interval 11.73 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

The EORTC QLQ-LC13 is comprised of 13 lung cancer-specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Chest pain were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of chest pain. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
TTCD in Participant-Reported Chest Pain, as Measured by EORTC QLQ-LC13	NA months The median and 95% CI was not estimable due to insufficient number of participants with events.	NA months The median and 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: FAS included all randomized participants whether or not the participants received the assigned treatment.

The EORTC QLQ-LC13 is comprised of 13 lung cancer-specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Cough were scored on a 4-point scale: 1=not at all to 4=very much. Scores are linearly transformed to a range of 0 to 100. A higher score indicates a worse level of cough. TTCD was defined as time from the date of randomization until the first confirmed clinically meaningful deterioration. Confirmed clinically meaningful deterioration in symptoms was defined as a score increase of ≥ 10-point from baseline in a symptom score that must be held for at least two consecutive assessments or an initial increase ≥ 10-point from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=273 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=269 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
TTCD in Participant-Reported Cough, as Measured by EORTC QLQ-LC13	NA months The median and 95% CI was not estimable due to insufficient number of participants with events.	NA months The median and 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: From study start up to 90 days after last dose (up to approximately 40.8 months)

Population: Safety-evaluable set included all participants randomized to the study and who received at least one dose of study treatment.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=272 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=267 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Number of Participants With Adverse Events (AEs)	267 Participants	262 Participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57 and treatment discontinuation visit (each cycle=21 days) (Up to 40 months)

Population: Safety-evaluable set included all participants randomized to the study and who received at least one dose of study treatment.

The EORTC IL46 is a validated single-item question that assesses overall side effect impact, i.e. "To what extent have you been troubled with side-effects from your treatment ". Each item is scored on a 4-point scale (1= Not at all, 2= A Little, 3= Quite a Bit, and 4= Very Much).

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=272 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy n=267 Participants Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 21 Day 1 · A Little	33 Participants	16 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 21 Day 1 · Quite a bit	6 Participants	10 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 21 Day 1 · Very Much	1 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 23 Day 1 · Not at all	19 Participants	14 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 23 Day 1 · A Little	26 Participants	17 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 23 Day 1 · Quite a bit	2 Participants	3 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 23 Day 1 · Very Much	1 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 25 Day 1 · Not at all	14 Participants	12 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 25 Day 1 · A Little	14 Participants	15 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 25 Day 1 · Quite a bit	5 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 25 Day 1 · Very Much	0 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 27 Day 1 · Not at all	8 Participants	12 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 27 Day 1 · A Little	8 Participants	11 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 27 Day 1 · Quite a bit	4 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 27 Day 1 · Very Much	1 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 29 Day 1 · Not at all	7 Participants	8 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 29 Day 1 · A Little	6 Participants	11 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 29 Day 1 · Quite a bit	4 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 29 Day 1 · Very Much	0 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 31 Day 1 · Not at all	6 Participants	8 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 31 Day 1 · A Little	4 Participants	7 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 31 Day 1 · Quite a bit	1 Participants	4 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 31 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 33 Day 1 · Not at all	5 Participants	6 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 33 Day 1 · A Little	5 Participants	12 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 33 Day 1 · Quite a bit	1 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 33 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 35 Day 1 · Not at all	4 Participants	4 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 35 Day 1 · A Little	4 Participants	9 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 35 Day 1 · Quite a bit	0 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 35 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 37 Day 1 · Not at all	5 Participants	3 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 37 Day 1 · A Little	3 Participants	8 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 37 Day 1 · Quite a bit	1 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 37 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 39 Day 1 · Not at all	5 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 39 Day 1 · A Little	5 Participants	9 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 39 Day 1 · Quite a bit	1 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 39 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 41 Day 1 · Not at all	4 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 41 Day 1 · A Little	3 Participants	9 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 41 Day 1 · Quite a bit	1 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 41 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 43 Day 1 · Not at all	5 Participants	4 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 43 Day 1 · A Little	4 Participants	6 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 43 Day 1 · Quite a bit	0 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 43 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 45 Day 1 · Not at all	4 Participants	4 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 45 Day 1 · A Little	2 Participants	5 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 45 Day 1 · Quite a bit	1 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 45 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 47 Day 1 · Not at all	3 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 47 Day 1 · A Little	2 Participants	8 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 47 Day 1 · Quite a bit	1 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 47 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 49 Day 1 · Not at all	4 Participants	3 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 49 Day 1 · A Little	0 Participants	5 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 49 Day 1 · Quite a bit	1 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 49 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 51 Day 1 · Not at all	2 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 51 Day 1 · A Little	2 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 51 Day 1 · Quite a bit	0 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 51 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 53 Day 1 · Not at all	2 Participants	3 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 53 Day 1 · A Little	2 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 53 Day 1 · Quite a bit	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 53 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 55 Day 1 · Not at all	0 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 55 Day 1 · A Little	2 Participants	1 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 55 Day 1 · Quite a bit	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 55 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 57 Day 1 · Not at all	0 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 57 Day 1 · A Little	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 57 Day 1 · Quite a bit	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 57 Day 1 · Very Much	0 Participants	0 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Treatment Discontinuation Visit · Not at all	58 Participants	35 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Treatment Discontinuation Visit · A Little	50 Participants	61 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Treatment Discontinuation Visit · Quite a bit	29 Participants	37 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Treatment Discontinuation Visit · Very Much	15 Participants	12 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 2 Day 1 · Not at all	100 Participants	73 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 2 Day 1 · A Little	112 Participants	125 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Baseline · Not at all	207 Participants	192 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Baseline · A Little	33 Participants	44 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Baseline · Quite a bit	8 Participants	12 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Baseline · Very Much	8 Participants	3 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 2 Day 1 · Quite a bit	32 Participants	41 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 2 Day 1 · Very Much	14 Participants	9 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 3 Day 1 · Not at all	89 Participants	70 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 3 Day 1 · A Little	113 Participants	112 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 3 Day 1 · Quite a bit	32 Participants	40 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 3 Day 1 · Very Much	8 Participants	11 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 4 Day 1 · Not at all	86 Participants	64 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 4 Day 1 · A Little	113 Participants	107 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 4 Day 1 · Quite a bit	30 Participants	37 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 4 Day 1 · Very Much	10 Participants	8 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 5 Day 1 · Not at all	86 Participants	65 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 5 Day 1 · A Little	94 Participants	104 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 5 Day 1 · Quite a bit	34 Participants	34 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 5 Day 1 · Very Much	11 Participants	5 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 7 Day 1 · Not at all	81 Participants	59 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 7 Day 1 · A Little	82 Participants	84 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 7 Day 1 · Quite a bit	23 Participants	29 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 7 Day 1 · Very Much	8 Participants	7 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 9 Day 1 · Not at all	70 Participants	49 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 9 Day 1 · A Little	73 Participants	73 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 9 Day 1 · Quite a bit	24 Participants	25 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 9 Day 1 · Very Much	3 Participants	5 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 11 Day 1 · Not at all	61 Participants	41 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 11 Day 1 · A Little	68 Participants	69 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 11 Day 1 · Quite a bit	14 Participants	16 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 11 Day 1 · Very Much	1 Participants	7 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 13 Day 1 · Not at all	57 Participants	44 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 13 Day 1 · A Little	56 Participants	40 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 13 Day 1 · Quite a bit	12 Participants	17 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 13 Day 1 · Very Much	2 Participants	10 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 15 Day 1 · Not at all	47 Participants	33 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 15 Day 1 · A Little	42 Participants	46 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 15 Day 1 · Quite a bit	13 Participants	16 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 15 Day 1 · Very Much	1 Participants	3 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 17 Day 1 · Not at all	42 Participants	28 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 17 Day 1 · A Little	42 Participants	30 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 17 Day 1 · Quite a bit	4 Participants	17 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 17 Day 1 · Very Much	1 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 19 Day 1 · Not at all	41 Participants	23 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 19 Day 1 · A Little	31 Participants	29 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 19 Day 1 · Quite a bit	7 Participants	6 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 19 Day 1 · Very Much	1 Participants	2 Participants
Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) Cycle 21 Day 1 · Not at all	25 Participants	18 Participants

SECONDARY outcome

Timeframe: Predose Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at treatment completion (TC)/early discontinuation (ED); and 0.5 hour (h) postdose Day 1 of Cycle 1 (each cycle=21 days) (Up to 40 months)

Population: Atezolizumab PK evaluable population included all randomized participants who received any dose of atezolizumab and who have at least one post-baseline pharmacokinetic (PK) sample available. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=256 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Serum Concentration of Atezolizumab Predose: Cycle 1 Day 1	NA micrograms per milliliter (μg/mL) Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable because the values were below the level of detection.	—
Serum Concentration of Atezolizumab Postdose: Cycle 1 Day 1	326 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 278.4	—
Serum Concentration of Atezolizumab Predose: Cycle 2 Day 1	67.3 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 128.4	—
Serum Concentration of Atezolizumab Predose: Cycle 3 Day 1	106 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 81.9	—
Serum Concentration of Atezolizumab Predose: Cycle 4 Day 1	143 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 52.7	—
Serum Concentration of Atezolizumab Predose: Cycle 8 Day 1	173 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 122.1	—
Serum Concentration of Atezolizumab Predose: Cycle 12 Day 1	192 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 66.1	—
Serum Concentration of Atezolizumab Predose: Cycle 16 Day 1	149 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 299.6	—
Serum Concentration of Atezolizumab TC/ED	97.5 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 386.1	—

SECONDARY outcome

Timeframe: Predose Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and at TC/ED; and 0.5 hour (h) postdose Day 1 of Cycle 1 (each cycle=21 days) (Up to 40 months)

Population: Tiragolumab PK evaluable population included all randomized participants who received any dose of tiragolumab and who have at least one post-baseline PK sample available. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=257 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Serum Concentration of Tiragolumab Postdose: Cycle 1 Day 1	137 μg/mL Geometric Coefficient of Variation 1107.3	—
Serum Concentration of Tiragolumab Predose: Cycle 1 Day 1	NA μg/mL Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable because the values were below the level of detection.	—
Serum Concentration of Tiragolumab Predose: Cycle 2 Day 1	32.2 μg/mL Geometric Coefficient of Variation 115.7	—
Serum Concentration of Tiragolumab Predose: Cycle 3 Day 1	51.2 μg/mL Geometric Coefficient of Variation 64.5	—
Serum Concentration of Tiragolumab Predose: Cycle 4 Day 1	69.2 μg/mL Geometric Coefficient of Variation 53.4	—
Serum Concentration of Tiragolumab Predose: Cycle 8 Day 1	79.6 μg/mL Geometric Coefficient of Variation 101.1	—
Serum Concentration of Tiragolumab Predose: Cycle 12 Day 1	89.2 μg/mL Geometric Coefficient of Variation 91.9	—
Serum Concentration of Tiragolumab Predose: Cycle 16 Day 1	67.3 μg/mL Geometric Coefficient of Variation 366.0	—
Serum Concentration of Tiragolumab TC/ED	45.3 μg/mL Geometric Coefficient of Variation 331.6	—

SECONDARY outcome

Timeframe: Up to approximately 40 months

Population: Safety-evaluable set included all participants randomized to the study and who received at least one dose of study treatment. Overall number analyzed is the number of participants with data available for analysis.

Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=254 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADAs) to Atezolizumab	90 Participants	—

SECONDARY outcome

Timeframe: Up to approximately 40 months

Participants who received tiragolumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.

Outcome measures

Outcome measures
Measure	Placebo + Pembrolizumab + Chemotherapy n=254 Participants Participants received pembrolizumab at a fixed dose 200 mg, placebo, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with pembrolizumab, placebo and pemetrexed at the same dose as induction treatment, as IV infusion, on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.	Tiragolumab + Atezolizumab + Chemotherapy Participants received atezolizumab at a fixed dose of 1200 mg, tiragolumab at a fixed dose of 600 mg, pemetrexed, 500 mg/m\^2, and either carboplatin, AUC 5 of 5 or cisplatin 75 mg/m\^2 as IV infusion on Day 1 of each 21-day cycle as induction treatment (Cycles 1-4). Participants then received maintenance treatment with atezolizumab, tiragolumab and pemetrexed at the same dose as induction treatment as IV infusion on Day 1 of each 21-day cycle from Cycle 5 onwards, until PD, loss of clinical benefit or unacceptable toxicity.
Number of Participants With Treatment-Emergent ADAs to Tiragolumab	2 Participants	—

Adverse Events

Placebo + Pembrolizumab + Chemotherapy

Serious events: 142 serious events

Other events: 262 other events

Deaths: 117 deaths

Tiragolumab + Atezolizumab + Chemotherapy

Serious events: 147 serious events

Other events: 251 other events

Deaths: 146 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 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