Trial Outcomes & Findings for A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer (NCT NCT04300647)

Last Updated: 2026-03-12

Results Overview

ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR=Disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target or non-target) have reduction in short axis to \<10 millimeters (mm). PR=At least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. The study enrolled participants with measurable disease as determined by the investigator. Participants found to have non-measurable disease at baseline according to RECIST v1.1 (through IRC assessment or Protocol Deviations) were only considered responders if they achieved a CR. Percentages have been rounded off.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

172 participants

Primary outcome timeframe

From randomization up to approximately 17 months

Results posted on

2026-03-12

Participant Flow

A total of 172 participants took part in the study at 59 investigative sites across 17 countries from 30 June 2020 to 24 February 2025. 1 participant was enrolled but not treated. The study is considered "Completed" because all the pre-planned study activities and analyses have been performed.

Participants with programmed death-ligand 1 (PDL1)-positive cervical cancer in the pre-crossover period were randomized in a 3:1 ratio to receive either atezolizumab plus tiragolumab or atezolizumab monotherapy. Participants in the atezolizumab monotherapy arm with unequivocal disease progression (PD) were given the option to crossover and receive atezolizumab + tiragolumab in the crossover period. Crossover was allowed at investigator's discretion, after consultation with Medical Monitor.

Participant milestones

Participant milestones
Measure	Pre-crossover: Atezolizumab Monotherapy Participants received atezolizumab, 1200 milligrams (mg), as an intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-Crossover STARTED	45	127	0
Pre-Crossover COMPLETED	0	0	0
Pre-Crossover NOT COMPLETED	45	127	0
Post-Crossover STARTED	0	0	17
Post-Crossover COMPLETED	0	0	0
Post-Crossover NOT COMPLETED	0	0	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Pre-crossover: Atezolizumab Monotherapy Participants received atezolizumab, 1200 milligrams (mg), as an intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-Crossover Death	22	89	0
Pre-Crossover Withdrawal by Subject	4	8	0
Pre-Crossover Lost to Follow-up	1	3	0
Pre-Crossover Study Ended by Sponsor	6	14	0
Pre-Crossover Reason not Specified	2	13	0
Pre-Crossover Discontinued Due to PD, Moved to Crossover Period	10	0	0
Post-Crossover Death	0	0	10
Post-Crossover Withdrawal by Subject	0	0	1
Post-Crossover Lost to Follow-up	0	0	1
Post-Crossover Study Ended by Sponsor	0	0	5

Baseline Characteristics

A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Total n=171 Participants Total of all reporting groups
Age, Continuous	51.0 years STANDARD_DEVIATION 11.8 • n=9 Participants	50.8 years STANDARD_DEVIATION 11.8 • n=9 Participants	50.9 years STANDARD_DEVIATION 11.7 • n=18 Participants
Sex: Female, Male Female	45 Participants n=9 Participants	126 Participants n=9 Participants	171 Participants n=18 Participants
Sex: Female, Male Male	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=18 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=9 Participants	18 Participants n=9 Participants	25 Participants n=18 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=9 Participants	81 Participants n=9 Participants	113 Participants n=18 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=9 Participants	27 Participants n=9 Participants	33 Participants n=18 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=9 Participants	3 Participants n=9 Participants	6 Participants n=18 Participants
Race (NIH/OMB) Asian	6 Participants n=9 Participants	16 Participants n=9 Participants	22 Participants n=18 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Black or African American	1 Participants n=9 Participants	1 Participants n=9 Participants	2 Participants n=18 Participants
Race (NIH/OMB) White	28 Participants n=9 Participants	79 Participants n=9 Participants	107 Participants n=18 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=9 Participants	27 Participants n=9 Participants	34 Participants n=18 Participants
ECOG Performance Status ECOG Performance Status 0	23 Participants n=9 Participants	55 Participants n=9 Participants	78 Participants n=18 Participants
ECOG Performance Status ECOG Performance Status 1	22 Participants n=9 Participants	71 Participants n=9 Participants	93 Participants n=18 Participants
Prior Use of Chemoradiotherapy or Radiotherapy Yes	36 Participants n=9 Participants	98 Participants n=9 Participants	134 Participants n=18 Participants
Prior Use of Chemoradiotherapy or Radiotherapy No	9 Participants n=9 Participants	28 Participants n=9 Participants	37 Participants n=18 Participants
Treatment History Recurrent Disease	26 Participants n=9 Participants	65 Participants n=9 Participants	91 Participants n=18 Participants
Treatment History Persistent Disease	19 Participants n=9 Participants	61 Participants n=9 Participants	80 Participants n=18 Participants

PRIMARY outcome

Timeframe: From randomization up to approximately 17 months

Population: Treated population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Independent Review Committee (IRC)-Assessed Objective Response Rate (ORR)	15.6 percentage of participants Interval 6.5 to 29.5	19.0 percentage of participants Interval 12.6 to 27.0	—

SECONDARY outcome

Timeframe: Up to approximately 50.3 months

Population: Treated population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received. Crossover population included all participants randomized to the atezolizumab monotherapy arm who crossed over to the tiragolumab plus atezolizumab arm, and received at least any dose of tiragolumab after cross-over but not prior to cross-over.

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab n=17 Participants Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre- and Post-crossover Periods: Number of Participants With Adverse Events (AEs)	41 Participants	118 Participants	14 Participants

SECONDARY outcome

Timeframe: First occurrence of a documented objective response to the date of PD or death from any cause, whichever occurred first (up to approximately 17 months)

DOR was defined for participants who had objective response (OR) as time from first occurrence of a documented OR (CR/PR) to date of PD or death from any cause (whichever occurred first), determined by IRC per RECIST v1.1. CR=Disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to \<10 mm. PR=≥30% decrease in SOD of all target lesions, taking as reference baseline SOD, in absence of CR. PD = ≥ 20% increase in SOD of target lesions, taking as reference smallest SOD at prior timepoints (including baseline); in addition to relative increase of 20%, SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s). Study enrolled participants with measurable disease as per investigator. Participants who had non-measurable disease at baseline according to RECIST v1.1 (IRC assessment or Protocol Deviations) were only considered responders if they achieved CR.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=7 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=24 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: IRC-assessed Duration of Response (DOR)	NA months Interval 6.5 to NA: the median duration of ORR was not reached due to low number of participants with events.	11.8 months Interval 6.7 to NA: not estimable due to low number of participants with events.	—

SECONDARY outcome

Timeframe: From randomization up to approximately 17 months

Population: Treated population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received.

DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD), as determined by the IRC according to RECIST v1.1. CR and PR were defined the same as in the description of primary outcome measure (OM), ORR. SD=Neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. Participants were classified as SD only if SD was observed on two consecutive assessments ≥6 weeks apart. PD = ≥ 20% increase in SOD of target lesions, taking as reference smallest SOD at prior timepoints (including baseline); in addition to relative increase of 20%, SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s). Study enrolled participants with measurable disease as per the investigator. Participants who had non-measurable disease at baseline per RECIST v1.1 (IRC assessment or Protocol Deviations) were only considered responders if they achieved CR.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: IRC-assessed Disease Control Rate (DCR)	20.0 percentage of participants Interval 9.6 to 34.6	31.0 percentage of participants Interval 23.0 to 39.8	—

SECONDARY outcome

Timeframe: From randomization up to approximately 17 months

Population: Treated population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received.

BCR was defined as the percentage of participants with a CR, PR, or SD, as determined by the investigator according to RECIST v1.1. CR=Disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to \<10 mm. PR=At least a 30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD=Neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. Participants were classified as SD only if SD was observed on two consecutive assessments ≥6 weeks apart. PD=At least 20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline); in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s). Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Investigator-assessed Best Clinical Response (BCR) Rate	33.3 percentage of participants Interval 20.0 to 49.0	44.4 percentage of participants Interval 35.6 to 53.6	—

SECONDARY outcome

Timeframe: First occurrence of a documented clinical response to the date of PD or death from any cause, whichever occurred first (up to approximately 17 months)

Duration of BCR was defined for BCR responders as the time from first occurrence of a documented response (CR, PR, or SD) to date of PD or death from any cause (whichever occurred first), as clinically determined by the investigator according to RECIST v1.1. CR=Disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to \<10 mm. PR = ≥30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD=Neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. Participants were classified as SD only if SD was observed on two consecutive assessments ≥6 weeks apart. PD = ≥20% increase in SOD of target lesions, taking as reference smallest SOD at prior timepoints (including baseline); in addition to relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s).

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=15 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=56 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Investigator-assessed Duration of BCR	7.0 months Interval 5.6 to NA: not estimable due to low number of events.	5.5 months Interval 4.2 to 8.7	—

SECONDARY outcome

Timeframe: From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 17 months)

Population: Treated Population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received.

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

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: IRC-assessed Progression-free Survival (PFS)	1.9 months Interval 1.5 to 3.0	2.8 months Interval 1.7 to 4.1	—

SECONDARY outcome

Timeframe: At Month 6

Population: Treated Population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received. Overall number analyzed are number of participants with data available for analysis.

PFS rate was defined as the percentage of participants who were event-free at 6 months post-randomization, as determined by the IRC according to RECIST v1.1. PFS was defined as the time from randomization to the first occurrence of PD or death from any cause (whichever occurred first), as determined by the IRC according to RECIST v1.1. PD was defined as at least 20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline); in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s)..

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=9 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=34 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: IRC-assessed PFS Rate at 6 Months	21.50 percentage of participants Interval 9.06 to 33.94	30.56 percentage of participants Interval 22.29 to 38.83	—

SECONDARY outcome

Timeframe: From randomization to death from any cause (up to approximately 17 months)

Population: Treated Population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received.

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

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=45 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=126 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Overall Survival (OS)	10.6 months Interval 7.4 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	11.0 months Interval 9.6 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	—

SECONDARY outcome

Timeframe: At Months 6 and 12

Population: Treated Population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received. 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 specified timepoints.

OS rate was defined as the percentage of participants who were still alive at 6 months and 12 months. OS was defined as the time of randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=26 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=86 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: OS Rate at 6 Months and 12 Months At Month 6	69.49 percentage of participants Interval 55.52 to 83.47	73.56 percentage of participants Interval 65.69 to 81.44	—
Pre-crossover Period: OS Rate at 6 Months and 12 Months At Month 12	37.88 percentage of participants Interval 17.38 to 58.38	47.19 percentage of participants Interval 36.63 to 57.76	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (1 cycle = 21 days)

Population: Pharmacokinetic (PK)-evaluable population included all participants who received any dose of study treatment 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 time point.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=108 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab Predose on Cycle 2 Day 1	33.0 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 70.2	—	—
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab Predose on Cycle 3 Day 1	49.3 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 66.9	—	—
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab Predose on Cycle 4 Day 1	58.9 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 77.5	—	—
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab Predose on Cycle 8 Day 1	80.5 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 65.2	—	—
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab Predose on Cycle 12 Day 1	83.7 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 68.0	—	—
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab Predose on Cycle 16 Day 1	92.7 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 36.9	—	—

SECONDARY outcome

Timeframe: At 30 minutes post-dose on Cycle 1 Day 1 (1 Cycle = 21 days)

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=83 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Maximum Serum Concentration (Cmax) of Tiragolumab	226 µg/mL Geometric Coefficient of Variation 28.8	—	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (1 cycle = 21 days)

Population: PK-evaluable population included all participants who received any dose of study treatment 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 time point.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=38 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=107 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Cmin of Atezolizumab Predose on Cycle 2 Day 1	89.8 µg/mL Geometric Coefficient of Variation 56.3	89.4 µg/mL Geometric Coefficient of Variation 54.7	—
Pre-crossover Period: Cmin of Atezolizumab Predose on Cycle 3 Day 1	139 µg/mL Geometric Coefficient of Variation 47.8	137 µg/mL Geometric Coefficient of Variation 53.1	—
Pre-crossover Period: Cmin of Atezolizumab Predose on Cycle 4 Day 1	175 µg/mL Geometric Coefficient of Variation 40.3	156 µg/mL Geometric Coefficient of Variation 64.0	—
Pre-crossover Period: Cmin of Atezolizumab Predose on Cycle 8 Day 1	188 µg/mL Geometric Coefficient of Variation 111.2	212 µg/mL Geometric Coefficient of Variation 52.2	—
Pre-crossover Period: Cmin of Atezolizumab Predose on Cycle 12 Day 1	207 µg/mL Geometric Coefficient of Variation 78.3	215 µg/mL Geometric Coefficient of Variation 52.1	—
Pre-crossover Period: Cmin of Atezolizumab Predose on Cycle 16 Day 1	235 µg/mL Geometric Coefficient of Variation 10.2	223 µg/mL Geometric Coefficient of Variation 32.9	—

SECONDARY outcome

Timeframe: At 30 minutes post-dose on Day 1 of Cycle 1 (1 cycle = 21 days)

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=38 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=112 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Cmax of Atezolizumab	522 µg/mL Geometric Coefficient of Variation 24.3	507 µg/mL Geometric Coefficient of Variation 31.6	—

SECONDARY outcome

Timeframe: Up to approximately 17 months

Population: ADA-evaluable population included participants with any ADA assessments, with participants grouped according to treatment received. Overall number analyzed is the number of participants with data available for analysis.

Participants were considered treatment-emergent ADA-positive if they were ADA negative at baseline or missing data but developed an ADA response following study drug administration (treatment-induced ADA response) or if they were ADA-positive at baseline and the titre of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titre units\[t.u\]) than the titre of the baseline sample (treatment-enhanced ADA response).

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=118 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab	0.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Up to approximately 17 months

Participants were considered treatment-emergent ADA-positive if they were ADA negative at baseline or missing data but developed an ADA response following study drug administration (treatment-induced ADA response) or if they were ADA-positive at baseline and the titre of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 t.u) than the titre of the baseline sample (treatment-enhanced ADA response). Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Pre-crossover: Atezolizumab Monotherapy n=35 Participants Pre-crossover: Participants received atezolizumab, 1200 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Pre-crossover: Atezolizumab + Tiragolumab n=116 Participants Participants received atezolizumab, 1200 mg, as an IV infusion Q3W, on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg, as an IV infusion, Q3W also on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.	Post Crossover: Atezolizumab + Tiragolumab Participants in the atezolizumab monotherapy arm with unequivocal PD crossed over \& received atezolizumab, 1200 mg, in combination with tiragolumab, 600 mg, as an IV infusion, Q3W on Day 1 of each 21-day cycle until PD, loss of clinical benefit, or unacceptable toxicity as determined by the investigator.
Pre-crossover Period: Percentage of Participants With ADAs to Atezolizumab	20.0 percentage of participants	11.2 percentage of participants	—

Adverse Events

Pre-crossover: Atezolizumab Monotherapy

Serious events: 12 serious events

Other events: 36 other events

Deaths: 23 deaths

Pre-crossover: Atezolizumab + Tiragolumab

Serious events: 42 serious events

Other events: 109 other events

Deaths: 89 deaths

Post Crossover: Atezolizumab + Tiragolumab

Serious events: 1 serious events

Other events: 14 other events

Deaths: 10 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