Trial Outcomes & Findings for A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (NCT NCT04256421)

NCT ID: NCT04256421

Last Updated: 2026-04-03

Results Overview

OS was defined as the time from randomization to death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

490 participants

Primary outcome timeframe

From randomization to death from any cause (up to approximately 24 months)

Results posted on

2026-04-03

Participant Flow

A total of 490 participants with untreated extensive-stage small cell lung cancer (ES-SCLC) took part in the study at 121 centers across 23 countries from 04 February 2020 to 31 July 2025.

Participants were randomized to receive Placebo + Atezolizumab (P+A) or Tiragolumab + Atezolizumab (T+A) with carboplatin \& etoposide as induction treatment, followed by either P+A or T+A as maintenance treatment. 1 participant from P+A arm and 4 from T+A arm were randomized but not treated.

Participant milestones

Participant milestones
Measure	Arm A: Placebo + Atezolizumab During induction treatment, participants received atezolizumab, 1200 milligrams (mg) followed by placebo and carboplatin, as an intravenous (IV) infusion, to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams/milliliter/minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 milligram per square meter (mg/m\^2) as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until disease progression (PD) or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Overall Study STARTED	247	243
Overall Study Safety-evaluable Set	246	239
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	247	243

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Placebo + Atezolizumab During induction treatment, participants received atezolizumab, 1200 milligrams (mg) followed by placebo and carboplatin, as an intravenous (IV) infusion, to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams/milliliter/minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 milligram per square meter (mg/m\^2) as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until disease progression (PD) or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Overall Study Death	200	205
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	12	12
Overall Study Study Ended by Sponsor	33	25

Baseline Characteristics

A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Placebo + Atezolizumab n=247 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=243 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Total n=490 Participants Total of all reporting groups
Age, Continuous	65.1 years STANDARD_DEVIATION 7.9 • n=5 Participants	64.5 years STANDARD_DEVIATION 8.2 • n=5 Participants	64.8 years STANDARD_DEVIATION 8.0 • n=10 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	81 Participants n=5 Participants	164 Participants n=10 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	162 Participants n=5 Participants	326 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	10 Participants n=5 Participants	17 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	229 Participants n=5 Participants	224 Participants n=5 Participants	453 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	9 Participants n=5 Participants	20 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	67 Participants n=5 Participants	63 Participants n=5 Participants	130 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=5 Participants	2 Participants n=10 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=5 Participants	3 Participants n=10 Participants
Race (NIH/OMB) White	174 Participants n=5 Participants	173 Participants n=5 Participants	347 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=5 Participants	8 Participants n=10 Participants

PRIMARY outcome

Timeframe: From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months)

Population: PAS: All randomized participants without presence or history of brain metastases at baseline.

PFS was defined as the time from randomization to the first documented PD as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) 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 on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm).

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=201 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=196 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed Progression-free Survival (PFS) in the Primary Analysis Set (PAS)	5.55 months Interval 5.36 to 5.85	5.36 months Interval 4.67 to 5.52

PRIMARY outcome

Timeframe: From randomization to death from any cause (up to approximately 24 months)

Population: PAS: All randomized participants without presence or history of brain metastases at baseline.

OS was defined as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=201 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=196 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Overall Survival (OS) in the PAS	13.14 months Interval 12.16 to 15.11	13.11 months Interval 10.84 to 14.39

SECONDARY outcome

Timeframe: From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months)

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.

PFS was defined as the time from randomization to the first documented PD as determined by the investigator with the use of RECIST v1.1 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 on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=247 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=243 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
PFS in the FAS	5.42 months Interval 4.47 to 5.65	5.06 months Interval 4.4 to 5.42

SECONDARY outcome

Timeframe: From randomization to death from any cause (up to approximately 24 months)

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.

OS was defined as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=247 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=243 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
OS in the FAS	12.91 months Interval 11.99 to 14.52	12.75 months Interval 10.84 to 14.29

SECONDARY outcome

Timeframe: From randomization up to approximately 24 months

Population: PAS: All randomized participants without presence or history of brain metastases at baseline.

ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have 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	Arm A: Placebo + Atezolizumab n=201 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=196 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed Confirmed Objective Response Rate (ORR) in the PAS	66.7 percentage of participants Interval 59.64 to 73.05	73.5 percentage of participants Interval 66.61 to 79.39

SECONDARY outcome

Timeframe: From randomization up to approximately 24 months

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.

ORR was defined as the percentage of participants with CR or PR as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have 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	Arm A: Placebo + Atezolizumab n=247 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=243 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed Confirmed ORR in the FAS	65.6 percentage of participants Interval 59.26 to 71.42	70.8 percentage of participants Interval 64.56 to 76.33

SECONDARY outcome

Timeframe: From the first occurrence of a documented confirmed objective response (OR) to PD or death from any cause, whichever occurred first (up to approximately 24 months)

Population: PAS: All randomized participants without presence or history of brain metastases at baseline. DOR was analyzed in confirmed responders by investigator.

DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD or death from any cause, whichever occurred first, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) must have 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. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=134 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=144 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed Duration of Response (DOR) in the PAS	5.59 months Interval 4.57 to 6.93	4.19 months Interval 4.14 to 4.6

SECONDARY outcome

Timeframe: From the first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 24 months)

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment. DOR was analyzed in confirmed responders by investigator.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=162 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=172 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed DOR in the FAS	5.11 months Interval 4.37 to 5.75	4.17 months Interval 4.07 to 4.37

SECONDARY outcome

Timeframe: Month 6, Month 12

Population: PAS: All randomized participants without presence or history of brain metastases at baseline. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

PFS rate at 6 months and 12 months was defined as the percentage of participants who were event-free at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the Kaplan-Meier (K-M) method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk).

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=84 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=67 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed PFS Rates at 6 Months and 12 Months in the PAS Month 6	42.42 percentage of participants Interval 35.54 to 49.31	35.15 percentage of participants Interval 28.41 to 41.9
Investigator-assessed PFS Rates at 6 Months and 12 Months in the PAS Month 12	17.29 percentage of participants Interval 11.9 to 22.69	14.21 percentage of participants Interval 9.06 to 19.35

SECONDARY outcome

Timeframe: Month 6, Month 12

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

PFS rate at 6 months and 12 months was defined as the percentage of participants who were event-free at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the K-M method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk).

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=92 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=74 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Investigator-assessed PFS Rates at 6 Months and 12 Months in the FAS Month 6	37.95 percentage of participants Interval 31.85 to 44.05	31.30 percentage of participants Interval 25.41 to 37.19
Investigator-assessed PFS Rates at 6 Months and 12 Months in the FAS Month 12	14.07 percentage of participants Interval 9.59 to 18.55	12.33 percentage of participants Interval 7.9 to 16.75

SECONDARY outcome

Timeframe: Month 12, Month 24

OS rate at 12 months and 24 months was defined as the percentage of participants who were alive at these specific time points. Percentages have been rounded off to the nearest decimal point. A point estimate of the event-free rate was a single, numerical value used to approximate the true event-free rate of the entire population at a specific point in time. This value was calculated from ordered data (Event, Censoring) of each participant, using the K-M method, accounting for censored observations (so event-free rates may not directly be calculated based only on participants remaining at risk).

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=112 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=103 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
OS Rates at 12 Months and 24 Months in the PAS Month 12	57.74 percentage of participants Interval 50.82 to 64.66	54.00 percentage of participants Interval 46.97 to 61.03
OS Rates at 12 Months and 24 Months in the PAS Month 24	27.68 percentage of participants Interval 20.43 to 34.94	19.56 percentage of participants Interval 13.16 to 25.96

SECONDARY outcome

Timeframe: Month 12, Month 24

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=133 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=125 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
OS Rates at 12 Months and 24 Months in the FAS Month 24	25.82 percentage of participants Interval 19.19 to 32.46	20.53 percentage of participants Interval 14.54 to 26.52
OS Rates at 12 Months and 24 Months in the FAS Month 12	55.84 percentage of participants Interval 49.58 to 62.1	52.82 percentage of participants Interval 46.49 to 59.15

SECONDARY outcome

Timeframe: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months)

Population: PAS: All randomized participants without presence or history of brain metastases at baseline.

TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in PF. TTCD was determined based on patient-reported PF (Items 1-5) as collected and measured by the EORTC QLQ-C30. The PF was measured on 4-point scale (1='Not at all' to 4='Very much'). A high score for the PF subscale represented a high/healthy level of functioning. The scale was linearly transformed so that each score ranged from 0 to 100. A score change of at least 10-point in PF subscale score was perceived by participants as clinically meaningful. Confirmed clinically meaningful deterioration was defined as a clinically meaningful decrease from baseline that was held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=201 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=196 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (PF) in the PAS	19.35 months Interval 19.35 to NA = Upper limit of 95% confidence interval (CI) was not estimable due to an insufficient number of participants with events.	15.67 months Interval 12.81 to NA = Upper limit of 95% CI was not estimable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months)

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=247 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=243 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
TTCD of EORTC QLQ-C30 Physical Functioning in the FAS	19.35 months Interval 12.42 to NA = Upper limit of 95% CI was not estimable due to an insufficient number of participants with events.	15.67 months Interval 11.83 to NA = Upper limit of 95% CI was not estimable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months)

Population: PAS: All randomized participants without presence or history of brain metastases at baseline.

TTCD was the time from randomization until the first confirmed clinically meaningful deterioration in patient-reported GHS/QoL. TTCD was determined based on patient-reported GHS/QoL (Items 29-30) as collected and measured by the EORTC QLQ-C30. GHS/QoL items were scored on a 7-point scale, ranging from "very poor" to "excellent". A high score for the GHS/QoL subscale represented a high health-related QoL. The scale was linearly transformed so that each score ranged from 0 to 100. A score change of at least 10-point in GHS/QoL subscale score was perceived by participants as clinically meaningful. Confirmed clinically meaningful deterioration was defined as a clinically meaningful decrease from baseline that was held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 3 weeks.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=201 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=196 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality-of-life (QoL) in the PAS	NA months NA = Median and 95% CI were not estimable due to an insufficient number of participants with events.	NA months Interval 14.55 to NA = Median and upper limit of 95% CI were not estimable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months)

Population: FAS: All randomized participants, whether or not the participant received the assigned treatment.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=247 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=243 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
TTCD of EORTC QLQ-C30 GHS/QoL in the FAS	NA months NA = Median and 95% CI were not estimable due to an insufficient number of participants with events.	NA months Interval 14.55 to NA = Median and upper limit of 95% CI were not estimable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to 58 months

Population: Safety-evaluable set: All randomized participants 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 adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study were also considered as AEs.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=246 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=239 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Number of Participants With Adverse Events (AEs)	245 Participants	238 Participants

SECONDARY outcome

Timeframe: Up to 58 months

Population: Safety-evaluable set: All randomized participants who received at least one dose of study treatment.

CRS=supraphysiologic response following administration of any immune therapy that results in activation/engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms may be progressive, including fever at onset, and may also include hypotension, capillary leak (hypoxia), and end-organ dysfunction. Severity of CRS was determined per ASTCT Consensus Grading Criteria, which categorizes CRS into 5 grades: Grade 1: Fever (≥38◦Celsius), with/without constitutional symptoms, in absence of hypotension \& hypoxia; Grade 2: Fever with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen; Grade 3: Fever with hypotension requiring one vasopressor, with/without vasopressin, and/or hypoxia requiring high-flow oxygen; Grade 4: Fever accompanied by hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive-pressure ventilation; Grade 5: death due to CRS. Only non zero values have been reported.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=246 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=239 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Number of Participants With Severity of Cytokine-release Syndrome (CRS), as Determined by the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Scale	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At the end of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days)

Population: Pharmacokinetic (PK)-evaluable set: All participants who received at least one dose of tiragolumab and who had at least one post-baseline PK sample available. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=218 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Minimum Serum Concentration (Cmin) of Tiragolumab Cycle 1	29.5 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 49.2	—
Minimum Serum Concentration (Cmin) of Tiragolumab Cycle 2	46.5 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 47.5	—
Minimum Serum Concentration (Cmin) of Tiragolumab Cycle 3	56.3 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 83.5	—
Minimum Serum Concentration (Cmin) of Tiragolumab Cycle 7	76.3 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 48.2	—
Minimum Serum Concentration (Cmin) of Tiragolumab Cycle 11	78.8 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 246	—
Minimum Serum Concentration (Cmin) of Tiragolumab Cycle 15	96.4 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 43.8	—

SECONDARY outcome

Timeframe: At the end of each Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days)

Population: PK-evaluable set: All participants who received at least one dose of atezolizumab and who had at least one post-baseline PK sample available. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=226 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=217 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Cmin of Atezolizumab Cycle 11	226 µg/mL Geometric Coefficient of Variation 37.3	244 µg/mL Geometric Coefficient of Variation 37
Cmin of Atezolizumab Cycle 15	198 µg/mL Geometric Coefficient of Variation 75.5	253 µg/mL Geometric Coefficient of Variation 36.6
Cmin of Atezolizumab Cycle 1	75.0 µg/mL Geometric Coefficient of Variation 63.2	75.4 µg/mL Geometric Coefficient of Variation 70.8
Cmin of Atezolizumab Cycle 2	121 µg/mL Geometric Coefficient of Variation 55.8	125 µg/mL Geometric Coefficient of Variation 38.4
Cmin of Atezolizumab Cycle 3	144 µg/mL Geometric Coefficient of Variation 49.8	155 µg/mL Geometric Coefficient of Variation 81.5
Cmin of Atezolizumab Cycle 7	205 µg/mL Geometric Coefficient of Variation 45.3	198 µg/mL Geometric Coefficient of Variation 46.4

SECONDARY outcome

Timeframe: Pre-dose and 30 minutes post end of infusion (EOI) on Day 1 of Cycle 1 (1 Cycle=21 days)

Population: PK-evaluable set: All participants who received at least one dose of tiragolumab and who had at least one post-baseline PK sample available. Overall number of participants analyzed is the number of participants with data available for analysis.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=213 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Maximum Serum Concentration (Cmax) of Tiragolumab	188 µg/mL Geometric Coefficient of Variation 24.2	—

SECONDARY outcome

Timeframe: Pre-dose and 30 minutes post EOI on Day 1 of Cycle 1 (1 Cycle=21 days)

Population: PK-evaluable set: All participants who received at least one dose of atezolizumab and who had at least one post-baseline PK sample available. Overall number analyzed is the number of participants with data available for analysis.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=233 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=224 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Cmax of Atezolizumab	398 µg/mL Geometric Coefficient of Variation 28.2	405 µg/mL Geometric Coefficient of Variation 23.0

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8,12, 16 and at treatment discontinuation (TD) visit (up to 24 months) (1 Cycle=21 days)

Population: Tiragolumab ADA-evaluable set: All participants who received at least one dose of tiragolumab treatment and with an ADA assay result from at least one sample result. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Participants were considered to be ADA-positive if they were ADA-negative at baseline but developed an ADA response following tiragolumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such at least 0.60 titer unit (t.u.) greater than the baseline titer result (treatment-enhanced ADA response). The total number of participants who developed ADAs to tiragolumab was determined by summing the ADA-positive participants across all timepoints.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=235 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab Participants With Positive Sample at Baseline	2 Participants	—
Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab Participants Positive for Treatment Emergent ADAs	3 Participants	—
Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab Treatment-induced ADAs	3 Participants	—
Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab Treatment-enhanced ADAs	0 Participants	—

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8,12, 16 and at TD visit (up to 24 months) (1 Cycle=21 days)

Population: Atezolizumab ADA-evaluable set: All participants who received at least one dose of atezolizumab treatment and with an ADA assay result from at least one sample result. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Participants were considered to be ADA-positive if they were ADA-negative at baseline but developed an ADA response following atezolizumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such at least 0.60 t.u. greater than the baseline titer result (treatment-enhanced ADA response). The total number of participants who developed ADAs to tiragolumab was determined by summing the ADA-positive participants across all timepoints.

Outcome measures

Outcome measures
Measure	Arm A: Placebo + Atezolizumab n=244 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by placebo and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab + placebo on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.	Arm B: Tiragolumab + Atezolizumab n=236 Participants During induction treatment, participants received atezolizumab, 1200 mg followed by tiragolumab, 600 mg, and carboplatin, as an IV infusion, to achieve an initial target AUC of 5 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles. Participants also received etoposide, 100 mg/m\^2 as IV infusion on Days 2 and 3 of each 21-day cycle for 4 cycles. Thereafter, participants received maintenance treatment with atezolizumab+ tiragolumab on Day 1 of each 21-day cycle at the same dose as during induction treatment until PD or loss of clinical benefit.
Number of Participants With ADAs to Atezolizumab Participants With Positive Sample at Baseline	2 Participants	1 Participants
Number of Participants With ADAs to Atezolizumab Participants Positive for Treatment Emergent ADAs	48 Participants	22 Participants
Number of Participants With ADAs to Atezolizumab Treatment-induced ADAs	48 Participants	22 Participants
Number of Participants With ADAs to Atezolizumab Treatment-enhanced ADAs	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose; Day 1 of Cycles 1, 2, 3, and 4

The EQ-5D-5L is a validated self-report health status questionnaire that was used to calculate a health status utility score for use in health economic analyses. There were two components to the EQ-5D-5L: a five-item health state profile that assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analog scale (VAS) that measured health state. The EQ VAS records the participant's self-rated health on a vertical visual analogue scale ranging from 0 to 100. A single composite score was calculated based on the responses as an indicator of the participant's health status. The scale ranges 0-100, 0=worst health and 100=best health.

Outcome measures

Outcome data not reported

Adverse Events

Arm A: Placebo + Atezolizumab

Serious events: 108 serious events

Other events: 235 other events

Deaths: 200 deaths

Arm B: Tiragolumab + Atezolizumab

Serious events: 109 serious events

Other events: 228 other events

Deaths: 207 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