Trial Outcomes & Findings for Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer (NCT NCT04665856)

Last Updated: 2026-02-13

Results Overview

PFS was defined as time from randomization to the first occurrence of disease progression (PD), as assessed by the investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

123 participants

Primary outcome timeframe

Up to 32.3 months

Results posted on

2026-02-13

Participant Flow

Participants were enrolled at 17 investigative sites in China. This study is still ongoing.

A total of 123 participants were randomized in the study in a 1:1 ratio to receive tiragolumab plus atezolizumab and carboplatin + etoposide (CE) or placebo plus atezolizumab and CE. One participant from the tiragolumab arm did not receive tiragolumab and hence was included in the placebo arm group for safety analysis.

Participant milestones

Participant milestones
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide Participants received atezolizumab, 1200 milligrams (mg), followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target area under the concentration-time curve (AUC) of 5 milligrams per mililiter per minute (mg/mL/min) as an intravenous (IV) infusion, once every 3 weeks (Q3W), on Day 1 of each 21-day cycle along with etoposide, 100 milligrams per square meter (mg/m\^2), as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Overall Study STARTED	62	61
Overall Study Safety Evaluable Set	63	60
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	62	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide Participants received atezolizumab, 1200 milligrams (mg), followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target area under the concentration-time curve (AUC) of 5 milligrams per mililiter per minute (mg/mL/min) as an intravenous (IV) infusion, once every 3 weeks (Q3W), on Day 1 of each 21-day cycle along with etoposide, 100 milligrams per square meter (mg/m\^2), as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Overall Study Site Terminated by Sponsor	1	0
Overall Study Withdrawal by Subject	2	0
Overall Study Lost to Follow-up	3	2
Overall Study Death	39	44
Overall Study Ongoing in study	17	15

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=62 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=61 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Total n=123 Participants Total of all reporting groups
Age, Continuous	60.9 years STANDARD_DEVIATION 8.0 • n=6 Participants	62.0 years STANDARD_DEVIATION 7.8 • n=6 Participants	61.4 years STANDARD_DEVIATION 7.9 • n=12 Participants
Sex: Female, Male Female	8 Participants n=6 Participants	8 Participants n=6 Participants	16 Participants n=12 Participants
Sex: Female, Male Male	54 Participants n=6 Participants	53 Participants n=6 Participants	107 Participants n=12 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	62 Participants n=6 Participants	61 Participants n=6 Participants	123 Participants n=12 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Asian	62 Participants n=6 Participants	61 Participants n=6 Participants	123 Participants n=12 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Black or African American	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) White	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants

PRIMARY outcome

Timeframe: Up to 32.3 months

Population: Primary Analysis Set (PAS) included all randomized participants without presence or history of brain metastases at baseline.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=56 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=54 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set (PAS)	5.39 months Interval 4.3 to 6.77	5.59 months Interval 4.53 to 7.89

PRIMARY outcome

Timeframe: Up to 32.3 months

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

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

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=56 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=54 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Overall Survival (OS) in the PAS	13.54 months Interval 10.35 to 22.44	18.69 months Interval 14.26 to 20.86

SECONDARY outcome

Timeframe: Up to 32.3 months

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

PFS was defined as time from randomization to the first occurrence of PD, as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=62 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=61 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
PFS in the FAS	5.39 months Interval 4.3 to 6.08	5.59 months Interval 4.47 to 7.89

SECONDARY outcome

Timeframe: Up to 32.3 months

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

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

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=62 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=61 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
OS in the FAS	14.88 months Interval 10.68 to 22.44	17.31 months Interval 12.48 to 20.37

SECONDARY outcome

Timeframe: Up to 32.3 months

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

ORR was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart as assessed by investigator according to RECIST v.1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters in the absence of CR. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=56 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=54 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS	58.9 percentage of participants Interval 45.01 to 71.63	81.5 percentage of participants Interval 68.13 to 90.3

SECONDARY outcome

Timeframe: Up to 32.3 months

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

ORR was defined as the percentage of participants with either a confirmed CR or PR on two consecutive occasions ≥4 weeks apart as assessed by investigator according to RECIST v.1.1. CR was defined as disappearance of all target lesions and 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 sum of diameters of target lesions, taking as reference the baseline sum of diameters in the absence of CR. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=62 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=61 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed Confirmed ORR in the FAS	59.7 percentage of participants Interval 46.46 to 71.7	77.0 percentage of participants Interval 64.2 to 86.46

SECONDARY outcome

Timeframe: Up to 32.3 months

Population: PAS included all randomized participants without presence or history of brain metastases at baseline. Overall number analyzed is the number of participants with objective response i.e., responders.

DOR was defined as the time interval from the date of the first occurrence of a confirmed objective response until the first date of PD as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first. DOR was evaluated for participants who had an objective response of CR or PR. CR was defined as the disappearance of all target lesions and 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 sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=33 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=44 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed Duration of Response (DOR) in the PAS	5.45 months Interval 3.91 to 5.95	5.52 months Interval 4.11 to 8.54

SECONDARY outcome

Timeframe: Up to 32.3 months

Population: FAS included all randomized participants whether or not the participants received the assigned study treatment. Overall number analyzed is the number of participants with objective response i.e., responders.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=37 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=47 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed DOR in the FAS	5.45 months Interval 3.91 to 6.14	5.55 months Interval 4.17 to 7.92

SECONDARY outcome

Timeframe: Month 6, Month 12

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

PFS = time from randomization to the first occurrence of PD, per investigator per RECIST v1.1/ death from any cause, whichever occurs first. PFS rate at 6 and 12 = the percentage of participants who have not experienced PD per investigator per RECIST v1.1/ death from any cause at 6 and 12 months. PD =at least a 20% increase in the sum of diameters of target lesions, taking as reference the SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (K-M) method was used to estimate PFS rate. Percentages have been rounded off. Abbreviation used in Statistical Analysis section - Event Free Rate - EFR. The event free rate (for example the inv-PFS free rate of 10.24% at 12-months) used the K-M approach to estimate, which accounts for the censoring, the specific nature of time-to-event data. Naive calculation based on patient proportion will introduce bias.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=21 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=25 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS Month 6	39.11 percentage of participants Interval 26.09 to 52.14	47.20 percentage of participants Interval 33.76 to 60.64
Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS Month 12	10.24 percentage of participants Interval 1.91 to 18.57	27.69 percentage of participants Interval 15.51 to 39.87

SECONDARY outcome

Timeframe: Month 6, Month 12

PFS was defined as time from randomization to the first occurrence of PD, as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurs first. PFS rate at 6 months and 12 months 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 and 12 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate PFS rate. Percentages have been rounded off. The event free rate used the K-M approach to estimate, which accounts for the censoring, the specific nature of time-to-event data. Naive calculation based on patient proportion will introduce bias.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=23 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=28 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS Month 6	38.52 percentage of participants Interval 26.2 to 50.84	46.71 percentage of participants Interval 34.08 to 59.33
Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS Month 12	12.70 percentage of participants Interval 4.09 to 21.31	26.06 percentage of participants Interval 14.84 to 37.29

SECONDARY outcome

Timeframe: Month 12, Month 24

Population: PAS included 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 analyses. Number analyzed is the number of participants with data available at the specified timepoint.

OS was defined as the time from the date of randomization to the date of death from any cause. OS rate at 12 months and 24 months was defined as the percentage of participants who did not experience death from any cause at 12 months and 24 months. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=27 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=38 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Overall Survival Rate at 12 Months and 24 Months in the PAS Month 12	51.50 percentage of participants Interval 38.09 to 64.92	71.97 percentage of participants Interval 59.92 to 84.02
Overall Survival Rate at 12 Months and 24 Months in the PAS Month 24	32.94 percentage of participants Interval 19.97 to 45.92	32.44 percentage of participants Interval 19.55 to 45.33

SECONDARY outcome

Timeframe: Month 12, Month 24

Population: FAS included all randomized participants whether or not the participants received the assigned study treatment. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available at the specified timepoint.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=32 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=41 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Overall Survival Rates at 12 Months and 24 Months in the FAS 12 Months	54.73 percentage of participants Interval 42.07 to 67.39	68.61 percentage of participants Interval 56.91 to 80.32
Overall Survival Rates at 12 Months and 24 Months in the FAS 24 Months	34.65 percentage of participants Interval 22.24 to 47.05	32.11 percentage of participants Interval 20.06 to 44.16

SECONDARY outcome

Timeframe: Up to 66 months

An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 66 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 66 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1, 30 mins post end of infusion (EOI) (cycle length= 21 days)

Population: PK-evaluable population included all participants who received at least one dose of tiragolumab treatment and who have at least one post-baseline PK sample available.

Only sparse pharmacokinetic samples were collected in this study. With the focus on only Cmax and Cmin, there are no additional PK timepoints not reported

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=60 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Maximum Plasma Concentration (Cmax) of Tiragolumab	175 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 19.3	—

SECONDARY outcome

Timeframe: Pre-dose, Day 1 of Cycles 2, 3, 4, 8, 12, 16 (cycle length= 21 days)

Population: PK-evaluable population included all participants who received at least one dose of tiragolumab treatment and who have at least one post-baseline PK sample available. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=57 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose: Cycle 2 Day 1	27.0 μg/mL Geometric Coefficient of Variation 51.6	—
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose: Cycle 3 Day 1	39.4 μg/mL Geometric Coefficient of Variation 79.9	—
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose: Cycle 4 Day 1	48.0 μg/mL Geometric Coefficient of Variation 40.0	—
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose: Cycle 8 Day 1	64.5 μg/mL Geometric Coefficient of Variation 44.7	—
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose: Cycle 12 Day 1	53.6 μg/mL Geometric Coefficient of Variation 193	—
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose: Cycle 16 Day 1	71.9 μg/mL Geometric Coefficient of Variation 58.8	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1, 30 mins post EOI (cycle length= 21 days)

Population: Atezolizumab PK evaluable set included all participants who received at least one dose of atezolizumab treatment and who have at least one post-baseline PK sample available.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=63 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=60 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Cmax of Atezolizumab	355 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 28.9	370 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 36.5

SECONDARY outcome

Timeframe: Pre-dose, Day 1 of Cycles 2, 3, 4, 8, 12, 16 (cycle length= 21 days)

Population: Atezolizumab PK evaluable set included all participants who received at least one dose of atezolizumab treatment and who have at least one post-baseline PK sample available. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

Outcome measures

Outcome measures
Measure	Placebo + Atezolizumab + Carboplatin + Etoposide n=57 Participants Participants received atezolizumab, 1200 mg, followed by tiragolumab matching placebo, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 of each 21-day cycle along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab matching placebo given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.	Tiragolumab + Atezolizumab + Carboplatin + Etoposide n=58 Participants Participants received atezolizumab, 1200 mg, tiragolumab, 600 mg, and carboplatin, at a dose targeting initial target AUC of 5 mg/mL/min as an IV infusion, Q3W, on Day 1 along with etoposide, 100 mg/m\^2, as an IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles as induction treatment. (1 Cycle = 21 days). Participants then received maintenance treatment with atezolizumab, 1200 mg, followed by tiragolumab, 600 mg, given as an IV infusion, Q3W, from Day 1 of Cycle 5 until disease progression, loss of clinical benefit, unacceptable toxicity, or symptomatic deterioration attributed to disease progression.
Cmin of Atezolizumab Pre-dose: Cycle 2 Day 1	63.8 μg/mL Geometric Coefficient of Variation 76.5	68.1 μg/mL Geometric Coefficient of Variation 33.7
Cmin of Atezolizumab Pre-dose: Cycle 3 Day 1	88.5 μg/mL Geometric Coefficient of Variation 166	96.6 μg/mL Geometric Coefficient of Variation 46.6
Cmin of Atezolizumab Pre-dose: Cycle 4 Day 1	111 μg/mL Geometric Coefficient of Variation 88.6	99.2 μg/mL Geometric Coefficient of Variation 62.7
Cmin of Atezolizumab Pre-dose: Cycle 8 Day 1	151 μg/mL Geometric Coefficient of Variation 41.6	151 μg/mL Geometric Coefficient of Variation 31.8
Cmin of Atezolizumab Pre-dose: Cycle 16 Day 1	177 μg/mL Geometric Coefficient of Variation 55.0	169 μg/mL Geometric Coefficient of Variation 30.1
Cmin of Atezolizumab Pre-dose: Cycle 12 Day 1	139 μg/mL Geometric Coefficient of Variation 155	172 μg/mL Geometric Coefficient of Variation 35.0

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 49 months)

Outcome measures

Outcome data not reported

Adverse Events

Placebo + Atezolizumab + Carboplatin + Etoposide

Serious events: 23 serious events

Other events: 60 other events

Deaths: 40 deaths

Tiragolumab + Atezolizumab + Carboplatin + Etoposide

Serious events: 21 serious events

Other events: 60 other events

Deaths: 43 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