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Clinical Trial Results:
A Phase II, Safety, and Efficacy Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Patients With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer.

Summary
EudraCT number	2019-004895-21
Trial protocol	GB FR IT
Global end of trial date	24 Feb 2025

Results information
Results version number	v1(current)
This version publication date	07 Mar 2026
First version publication date	07 Mar 2026
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

WO42017

ISRCTN number

-

US NCT number

NCT04300647

WHO universal trial number (UTN)

-

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4058

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

24 Feb 2025

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

24 Feb 2025

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary purpose of this study was to evaluate the efficacy of tiragolumab plus atezolizumab and atezolizumab monotherapy in participants with metastatic and/or recurrent programmed death-ligand 1 (PD-L1)-positive cervical carcinoma.

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form (ICF).

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

30 Jun 2020

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

50 Months

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 1

Country: Number of subjects enrolled

Brazil: 12

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

Costa Rica: 7

Country: Number of subjects enrolled

Spain: 6

Country: Number of subjects enrolled

France: 30

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

Italy: 23

Country: Number of subjects enrolled

Korea, Republic of: 9

Country: Number of subjects enrolled

Mexico: 3

Country: Number of subjects enrolled

Panama: 3

Country: Number of subjects enrolled

Peru: 1

Country: Number of subjects enrolled

Poland: 16

Country: Number of subjects enrolled

Russian Federation: 18

Country: Number of subjects enrolled

Thailand: 1

Country: Number of subjects enrolled

Taiwan: 9

Country: Number of subjects enrolled

United States: 4

Worldwide total number of subjects

171

EEA total number of subjects

75

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

145

From 65 to 84 years

26

85 years and over

0

Subject disposition

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Recruitment details

A total of 172 participants with PDL1-positive cervical cancer 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.

Screening details

Participants in pre-crossover period were randomized to receive either atezolizumab + tiragolumab or atezolizumab monotherapy. Participants in atezolizumab monotherapy arm with unequivocal disease progression (PD) were given the option to crossover & receive atezolizumab + tiragolumab in crossover period, at the investigator's discretion.

Period 1 title

Pre-crossover

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

No

Pre-crossover: Atezolizumab Monotherapy

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

RO5541267

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

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

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

RO5541267

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

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.

Investigational medicinal product name

Tiragolumab

Investigational medicinal product code

RO7092284

Other name

MTIG7192A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

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.

Number of subjects in period 1	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Started	45	126
Completed	0	0
Not completed	45	126
Consent withdrawn by subject	4	7
Study Ended by Sponsor	6	14
Death	22	89
Discontinued due to PD, moved to Crossover period	10	-
Lost to follow-up	1	3
Reason not Specified	2	13

Period 2 title

Post-crossover

Is this the baseline period?

No

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Post Crossover: Atezolizumab + Tiragolumab

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

RO5541267

Other name

Tecentriq

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

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.

Investigational medicinal product name

Tiragolumab

Investigational medicinal product code

RO7092284

Other name

MTIG7192A

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

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.

Number of subjects in period 2	Post Crossover: Atezolizumab + Tiragolumab
Started	17
Completed	0
Not completed	17
Consent withdrawn by subject	1
Study Ended by Sponsor	5
Death	10
Lost to follow-up	1

Baseline characteristics

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Reporting group title

Pre-crossover: Atezolizumab Monotherapy

Reporting group description

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.

Reporting group title

Pre-crossover: Atezolizumab + Tiragolumab

Reporting group description

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.

Reporting group values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab	Total
Number of subjects	45	126	171
Age categorical
Units: participants
Age Continuous
Units: years
arithmetic mean (standard deviation)	51.0 ( 11.8 )	50.8 ( 11.8 )	-
Sex: Female, Male
Units: participants
Female	45	126	171
Male	0	0	0
ECOG Performance Status
ECOG Performance Status grades 0 or 1 were used for stratified randomization. Grade 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work).
Units: Subjects
ECOG Performance Status 0	23	55	78
ECOG Performance Status 1	22	71	93
Prior Use of Chemoradiotherapy or Radiotherapy
Prior use of chemotherapy or radiotherapy "yes" or "no" was used for stratified randomization.
Units: Subjects
Prior Use of Chemotherapy or Radiotherapy = Yes	36	98	134
Prior Use of Chemotherapy or Radiotherapy = No	9	28	37
Treatment History
Treatment history of recurrent versus persistent disease was used for stratified randomization.
Units: Subjects
Recurrent Disease	26	65	91
Persistent Disease	19	61	80
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	3	3	6
Asian	6	16	22
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	1	2
White	28	79	107
More than one race	0	0	0
Unknown or Not Reported	7	27	34
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	7	18	25
Not Hispanic or Latino	32	81	113
Unknown or Not Reported	6	27	33

End points

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Reporting group title

Pre-crossover: Atezolizumab Monotherapy

Reporting group description

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.

Reporting group title

Pre-crossover: Atezolizumab + Tiragolumab

Reporting group description

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.

Reporting group title

Post Crossover: Atezolizumab + Tiragolumab

Reporting group description

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.

Primary: Pre-crossover Period: Independent Review Committee (IRC)-assessed Objective Response Rate (ORR)

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End point title

Pre-crossover Period: Independent Review Committee (IRC)-assessed Objective Response Rate (ORR) ^[1]

End point description

ORR=percentage of participants with complete response (CR) or partial response (PR) on 2 consecutive occasions ≥4 weeks apart, as determined by IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR=Disappearance of all target lesions & non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to <10 millimeters (mm). PR=At least a 30% decrease in sum of diameters (SOD) of all target lesions, taking as reference baseline SOD, in absence of CR. The study enrolled participants with measurable disease as determined by investigator. Participants who had non-measurable disease at baseline according to RECIST v1.1 (IRC assessment/Protocol Deviations) were only considered responders if they achieved CR. Treated population=all randomized participants who received at least any dose of study treatment. Participants were grouped according to actual treatment received. Percentages have been rounded off.

End point type

Primary

End point timeframe

From randomization up to approximately 17 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint reports data for tiragolumab only.

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	45	126
Units: percentage of participants
number (confidence interval 95%)	15.6 (6.5 to 29.5)	19.0 (12.6 to 27.0)

No statistical analyses for this end point

Secondary: Pre- and Post-crossover Periods: Number of Participants With Adverse Events (AEs)

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End point title

Pre- and Post-crossover Periods: Number of Participants With Adverse Events (AEs)

End point description

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. 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.

End point type

Secondary

End point timeframe

Up to approximately 50.3 months

End point values	Pre-crossover: Atezolizumab Monotherapy	Post Crossover: Atezolizumab + Tiragolumab	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	45	17	126
Units: participants	41	14	118

No statistical analyses for this end point

Secondary: Pre-crossover Period: IRC-assessed Duration of Response (DOR)

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End point title

Pre-crossover Period: IRC-assessed Duration of Response (DOR)

End point description

DOR was defined for participants who had an objective response as time from first occurrence of documented OR (CR/PR) to date of PD/death from any cause (whichever occurred first), determined by IRC per RECIST v1.1. CR & PR=defined as outlined in the description of endpoint, ORR. PD=At least 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/Protocol Deviations) were only considered responders if they achieved CR. Treated population. DOR was assessed in participants with OR (CR/PR). 9999=median was not reached due to low number of participants with events; 99999=not estimable due to low number of events.

End point type

Secondary

End point timeframe

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

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	7	24
Units: months
median (confidence interval 95%)	9999 (6.5 to 99999)	11.8 (6.7 to 99999)

No statistical analyses for this end point

Secondary: Pre-crossover Period: IRC-assessed Disease Control Rate (DCR)

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End point title

Pre-crossover Period: IRC-assessed Disease Control Rate (DCR)

End point description

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 as outlined in the description for endpoint, 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=At least 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. Treated Population.

End point type

Secondary

End point timeframe

From randomization up to approximately 17 months

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	45	126
Units: percentage of participants
number (confidence interval 95%)	20.0 (9.6 to 34.6)	31.0 (23.0 to 39.8)

No statistical analyses for this end point

Secondary: Pre-crossover Period: Investigator-assessed Best Clinical Response (BCR) Rate

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End point title

Pre-crossover Period: Investigator-assessed Best Clinical Response (BCR) Rate

End point description

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. Treated population.

End point type

Secondary

End point timeframe

From randomization up to approximately 17 months

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	45	126
Units: percentage of participants
number (confidence interval 95%)	33.3 (20.0 to 49.0)	44.4 (35.6 to 53.6)

No statistical analyses for this end point

Secondary: Pre-crossover Period: Investigator-assessed Duration of BCR

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End point title

Pre-crossover Period: Investigator-assessed Duration of BCR

End point description

Duration of BCR was defined for BCR responders as the time from the first occurrence of a documented response (CR, PR, or SD) to the date of PD or death from any cause (whichever occurred first), as clinically determined by the investigator according to RECIST v1.1. CR & PR were defined as outlined in the description for endpoint, ORR. SD=Neither sufficient shrinkage to qualify for CR or 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). Treated population. Duration of BCR was assessed in participants with a clinical response. 99999: not estimable due to low number of events.

End point type

Secondary

End point 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)

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	15	56
Units: months
median (confidence interval 95%)	7.0 (5.6 to 99999)	5.5 (4.2 to 8.7)

No statistical analyses for this end point

Secondary: Pre-crossover Period: IRC-assessed Progression-free Survival (PFS)

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End point title

Pre-crossover Period: IRC-assessed Progression-free Survival (PFS)

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	45	126
Units: months
median (confidence interval 95%)	1.9 (1.5 to 3.0)	2.8 (1.7 to 4.1)

No statistical analyses for this end point

Secondary: Pre-crossover Period: IRC-assessed PFS Rate at 6 Months

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End point title

Pre-crossover Period: IRC-assessed PFS Rate at 6 Months

End point description

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

End point type

Secondary

End point timeframe

At Month 6

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	9	34
Units: percentage of participants
number (confidence interval 95%)	21.50 (9.06 to 33.94)	30.56 (22.29 to 38.83)

No statistical analyses for this end point

Secondary: Pre-crossover Period: Overall Survival (OS)

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End point title

Pre-crossover Period: Overall Survival (OS)

End point description

OS was defined as the time of randomization to death from any cause. Treated Population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received. 9999=Upper limit of the 95% CI was not estimable due to an insufficient number of participants with events.

End point type

Secondary

End point timeframe

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

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	45	126
Units: months
median (confidence interval 95%)	10.6 (7.4 to 9999)	11.0 (9.6 to 9999)

No statistical analyses for this end point

Secondary: Pre-crossover Period: OS Rate at 6 Months and 12 Months

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End point title

Pre-crossover Period: OS Rate at 6 Months and 12 Months

End point description

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. Treated Population included all randomized participants who received at least any dose of study treatment. Participants were grouped according to the actual treatment received. Number analyzed is number of participants with data available for analysis. n=number of participants with data available for analysis at specified timepoints.

End point type

Secondary

End point timeframe

At Months 6 and 12

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	26	86
Units: percentage of participants
number (confidence interval 95%)
6 Months (n=26, 86)	69.49 (55.52 to 83.47)	73.56 (65.69 to 81.44)
12 Months (n=5, 16)	37.88 (17.38 to 58.38)	47.19 (36.63 to 57.76)

No statistical analyses for this end point

Secondary: Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab

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End point title

Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab ^[2]

End point description

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. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at the specified time point.

End point type

Secondary

End point timeframe

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

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports data for tiragolumab only.

End point values	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	108
Units: micrograms per milliliter (µg/mL)
geometric mean (geometric coefficient of variation)
Predose on Cycle 2 Day 1 (n=108)	33.0 ( 70.2 )
Predose on Cycle 3 Day 1 (n=89)	49.3 ( 66.9 )
Predose on Cycle 4 Day 1 (n=81)	58.9 ( 77.5 )
Predose on Cycle 8 Day 1 (n=47)	80.5 ( 65.2 )
Predose on Cycle 12 Day 1 (n=21)	83.7 ( 68.0 )
Predose on Cycle 16 Day 1 (n=5)	92.7 ( 36.9 )

No statistical analyses for this end point

Secondary: Pre-crossover Period: Maximum Serum Concentration (Cmax) of Tiragolumab

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End point title

Pre-crossover Period: Maximum Serum Concentration (Cmax) of Tiragolumab ^[3]

End point description

PK-evaluable population included all participants who received any dose of study treatment and who had at least one post-baseline PK sample available. Number analyzed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports data for tiragolumab only.

End point values	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	83
Units: µg/mL
geometric mean (geometric coefficient of variation)	226 ( 28.8 )

No statistical analyses for this end point

Secondary: Pre-crossover Period: Cmin of Atezolizumab

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End point title

Pre-crossover Period: Cmin of Atezolizumab

End point description

PK-evaluable population included all participants who received any dose of study treatment and who had at least one post-baseline PK sample available. Number analyzed is the number of participants with data available for analysis. n = number of participants with data available for analysis at the specified time point.

End point type

Secondary

End point timeframe

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

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	38	107
Units: µg/mL
geometric mean (geometric coefficient of variation)
Predose on Cycle 2 Day 1 (n=38,107)	89.8 ( 56.3 )	89.4 ( 54.7 )
Predose on Cycle 3 Day 1 (n=27,87)	139 ( 47.8 )	137 ( 53.1 )
Predose on Cycle 4 Day 1 (n=22,82)	175 ( 40.3 )	156 ( 64.0 )
Predose on Cycle 8 Day 1 (n=15,46)	188 ( 111.2 )	212 ( 52.2 )
Predose on Cycle 12 Day 1 (n=7,22)	207 ( 78.3 )	215 ( 52.1 )
Predose on Cycle 16 Day 1 (n=2,6)	235 ( 10.2 )	223 ( 32.9 )

No statistical analyses for this end point

Secondary: Pre-crossover Period: Cmax of Atezolizumab

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End point title

Pre-crossover Period: Cmax of Atezolizumab

End point description

PK-evaluable population included all participants who received any dose of study treatment and who had at least one post-baseline PK sample available. Number analyzed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

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

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	38	112
Units: µg/mL
geometric mean (geometric coefficient of variation)	522 ( 24.3 )	507 ( 31.6 )

No statistical analyses for this end point

Secondary: Pre-crossover Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab

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End point title

Pre-crossover Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab ^[4]

End point description

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

End point type

Secondary

End point timeframe

Up to approximately 17 months

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint reports data for tiragolumab only.

End point values	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	118
Units: percentage of participants
number (not applicable)	0.0

No statistical analyses for this end point

Secondary: Pre-crossover Period: Percentage of Participants With ADAs to Atezolizumab

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End point title

Pre-crossover Period: Percentage of Participants With ADAs to Atezolizumab

End point description

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). ADA-evaluable population included participants with any ADA assessments, with participants grouped according to treatment received. Number analyzed is the number of participants with data available for analysis. Percentages have been rounded off.

End point type

Secondary

End point timeframe

Up to approximately 17 months

End point values	Pre-crossover: Atezolizumab Monotherapy	Pre-crossover: Atezolizumab + Tiragolumab
Number of subjects analysed	35	116
Units: percentage of participants
number (not applicable)	20.0	11.2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to approximately 50.3 months

Adverse event reporting additional description

Treated population. 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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.1

Reporting group title

Pre-crossover: Atezolizumab Monotherapy

Reporting group description

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.

Reporting group title

Post Crossover: Atezolizumab + Tiragolumab

Reporting group description

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.

Reporting group title

Pre-crossover: Atezolizumab + Tiragolumab

Reporting group description

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.

Serious adverse events	Pre-crossover: Atezolizumab Monotherapy	Post Crossover: Atezolizumab + Tiragolumab	Pre-crossover: Atezolizumab + Tiragolumab
Total subjects affected by serious adverse events
subjects affected / exposed	12 / 45 (26.67%)	1 / 17 (5.88%)	42 / 126 (33.33%)
number of deaths (all causes)	23	10	89
number of deaths resulting from adverse events	1	0	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tumour haemorrhage
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Raynaud's phenomenon
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Deep vein thrombosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Iliac vein occlusion
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	3 / 126 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperpyrexia
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Sarcoidosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	2 / 45 (4.44%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Female genital tract fistula
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Genital haemorrhage
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Interstitial lung disease
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lipase increased
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hip fracture
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	1 / 1	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dilated cardiomyopathy
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Middle cerebral artery stroke
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 45 (4.44%)	0 / 17 (0.00%)	3 / 126 (2.38%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Ileal stenosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Autoimmune hepatitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	3 / 126 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelocaliectasis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hypophysitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic abscess
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enterococcal sepsis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pyelitis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	2 / 126 (1.59%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Septic shock
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	3 / 126 (2.38%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal sepsis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia necrotising
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Helicobacter gastritis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Candida sepsis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Tumour lysis syndrome
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Pre-crossover: Atezolizumab Monotherapy	Post Crossover: Atezolizumab + Tiragolumab	Pre-crossover: Atezolizumab + Tiragolumab
Total subjects affected by non serious adverse events
subjects affected / exposed	36 / 45 (80.00%)	14 / 17 (82.35%)	109 / 126 (86.51%)
Vascular disorders
Superficial vein thrombosis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Hypertension
subjects affected / exposed	3 / 45 (6.67%)	0 / 17 (0.00%)	5 / 126 (3.97%)
occurrences all number	5	0	7
Embolism
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Hypotension
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
General disorders and administration site conditions
Face oedema
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	1	1	0
Chills
subjects affected / exposed	2 / 45 (4.44%)	1 / 17 (5.88%)	4 / 126 (3.17%)
occurrences all number	2	1	6
Asthenia
subjects affected / exposed	6 / 45 (13.33%)	1 / 17 (5.88%)	25 / 126 (19.84%)
occurrences all number	6	1	29
Fatigue
subjects affected / exposed	3 / 45 (6.67%)	2 / 17 (11.76%)	22 / 126 (17.46%)
occurrences all number	3	3	28
Pyrexia
subjects affected / exposed	6 / 45 (13.33%)	1 / 17 (5.88%)	21 / 126 (16.67%)
occurrences all number	10	1	24
Oedema peripheral
subjects affected / exposed	3 / 45 (6.67%)	1 / 17 (5.88%)	11 / 126 (8.73%)
occurrences all number	4	1	12
Vascular device occlusion
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Pain
subjects affected / exposed	2 / 45 (4.44%)	1 / 17 (5.88%)	2 / 126 (1.59%)
occurrences all number	2	1	2
Reproductive system and breast disorders
Vaginal discharge
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	3 / 126 (2.38%)
occurrences all number	1	1	3
Vulvovaginal pruritus
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	2	2	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	5 / 45 (11.11%)	0 / 17 (0.00%)	6 / 126 (4.76%)
occurrences all number	5	0	6
Nasal congestion
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	2 / 126 (1.59%)
occurrences all number	1	1	2
Pneumonitis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	2 / 126 (1.59%)
occurrences all number	0	1	2
Cough
subjects affected / exposed	2 / 45 (4.44%)	0 / 17 (0.00%)	11 / 126 (8.73%)
occurrences all number	2	0	12
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	9 / 126 (7.14%)
occurrences all number	1	1	9
Insomnia
subjects affected / exposed	2 / 45 (4.44%)	0 / 17 (0.00%)	7 / 126 (5.56%)
occurrences all number	2	0	8
Investigations
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 45 (0.00%)	2 / 17 (11.76%)	2 / 126 (1.59%)
occurrences all number	0	2	2
Blood creatinine increased
subjects affected / exposed	3 / 45 (6.67%)	2 / 17 (11.76%)	7 / 126 (5.56%)
occurrences all number	3	2	8
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 45 (0.00%)	2 / 17 (11.76%)	8 / 126 (6.35%)
occurrences all number	0	2	9
Aspartate aminotransferase increased
subjects affected / exposed	2 / 45 (4.44%)	1 / 17 (5.88%)	9 / 126 (7.14%)
occurrences all number	5	5	10
Alanine aminotransferase increased
subjects affected / exposed	3 / 45 (6.67%)	2 / 17 (11.76%)	9 / 126 (7.14%)
occurrences all number	7	6	9
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	1	1	1
Blood sodium decreased
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	0	1	1
Blood magnesium increased
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Weight decreased
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	9 / 126 (7.14%)
occurrences all number	1	1	9
Urine output decreased
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Blood bicarbonate decreased
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Platelet count increased
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	0	1	1
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	4 / 45 (8.89%)	1 / 17 (5.88%)	10 / 126 (7.94%)
occurrences all number	5	1	11
Fall
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	2 / 126 (1.59%)
occurrences all number	0	1	3
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	5 / 126 (3.97%)
occurrences all number	1	1	5
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	7 / 126 (5.56%)
occurrences all number	0	1	9
Headache
subjects affected / exposed	2 / 45 (4.44%)	0 / 17 (0.00%)	13 / 126 (10.32%)
occurrences all number	2	0	16
Hypoaesthesia
subjects affected / exposed	2 / 45 (4.44%)	1 / 17 (5.88%)	2 / 126 (1.59%)
occurrences all number	2	1	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	10 / 45 (22.22%)	5 / 17 (29.41%)	41 / 126 (32.54%)
occurrences all number	15	6	53
Lymphopenia
subjects affected / exposed	2 / 45 (4.44%)	2 / 17 (11.76%)	7 / 126 (5.56%)
occurrences all number	2	2	10
Neutropenia
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	6 / 126 (4.76%)
occurrences all number	1	1	10
Leukopenia
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	6 / 126 (4.76%)
occurrences all number	1	2	9
Eye disorders
Eyelids pruritus
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	4 / 45 (8.89%)	0 / 17 (0.00%)	5 / 126 (3.97%)
occurrences all number	4	0	6
Abdominal pain
subjects affected / exposed	1 / 45 (2.22%)	3 / 17 (17.65%)	19 / 126 (15.08%)
occurrences all number	1	3	24
Vomiting
subjects affected / exposed	7 / 45 (15.56%)	2 / 17 (11.76%)	20 / 126 (15.87%)
occurrences all number	7	2	25
Nausea
subjects affected / exposed	5 / 45 (11.11%)	3 / 17 (17.65%)	26 / 126 (20.63%)
occurrences all number	5	3	31
Diarrhoea
subjects affected / exposed	3 / 45 (6.67%)	3 / 17 (17.65%)	20 / 126 (15.87%)
occurrences all number	3	3	29
Constipation
subjects affected / exposed	5 / 45 (11.11%)	0 / 17 (0.00%)	16 / 126 (12.70%)
occurrences all number	7	0	22
Abdominal discomfort
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Melaena
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Abdominal distension
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	7 / 126 (5.56%)
occurrences all number	0	1	7
Hepatobiliary disorders
Biliary obstruction
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Skin and subcutaneous tissue disorders
Nail disorder
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Eczema
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	3 / 126 (2.38%)
occurrences all number	1	2	3
Hyperhidrosis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	0	1	1
Rash pruritic
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	0	1	1
Rash
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	11 / 126 (8.73%)
occurrences all number	1	1	13
Pruritus
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	27 / 126 (21.43%)
occurrences all number	0	1	37
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 45 (2.22%)	0 / 17 (0.00%)	8 / 126 (6.35%)
occurrences all number	1	0	9
Hydronephrosis
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	8 / 126 (6.35%)
occurrences all number	0	0	8
Haematuria
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	7 / 126 (5.56%)
occurrences all number	1	1	8
Endocrine disorders
Hypothyroidism
subjects affected / exposed	2 / 45 (4.44%)	2 / 17 (11.76%)	12 / 126 (9.52%)
occurrences all number	3	2	12
Hyperthyroidism
subjects affected / exposed	2 / 45 (4.44%)	0 / 17 (0.00%)	8 / 126 (6.35%)
occurrences all number	2	0	9
Adrenal insufficiency
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	0	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	7 / 45 (15.56%)	1 / 17 (5.88%)	18 / 126 (14.29%)
occurrences all number	7	1	27
Back pain
subjects affected / exposed	3 / 45 (6.67%)	1 / 17 (5.88%)	12 / 126 (9.52%)
occurrences all number	3	1	14
Pain in extremity
subjects affected / exposed	3 / 45 (6.67%)	0 / 17 (0.00%)	6 / 126 (4.76%)
occurrences all number	3	0	6
Muscle spasms
subjects affected / exposed	0 / 45 (0.00%)	0 / 17 (0.00%)	7 / 126 (5.56%)
occurrences all number	0	0	7
Infections and infestations
Pharyngitis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	1 / 126 (0.79%)
occurrences all number	0	1	1
Urinary tract infection
subjects affected / exposed	2 / 45 (4.44%)	1 / 17 (5.88%)	18 / 126 (14.29%)
occurrences all number	2	1	35
COVID-19
subjects affected / exposed	4 / 45 (8.89%)	1 / 17 (5.88%)	6 / 126 (4.76%)
occurrences all number	4	1	7
Urosepsis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Hypomagnesaemia
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	10 / 126 (7.94%)
occurrences all number	0	2	18
Hypercholesterolaemia
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Decreased appetite
subjects affected / exposed	3 / 45 (6.67%)	3 / 17 (17.65%)	21 / 126 (16.67%)
occurrences all number	3	3	22
Metabolic acidosis
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Hypervolaemia
subjects affected / exposed	0 / 45 (0.00%)	1 / 17 (5.88%)	0 / 126 (0.00%)
occurrences all number	0	1	0
Hypokalaemia
subjects affected / exposed	2 / 45 (4.44%)	1 / 17 (5.88%)	4 / 126 (3.17%)
occurrences all number	3	2	6
Hyperglycaemia
subjects affected / exposed	1 / 45 (2.22%)	1 / 17 (5.88%)	3 / 126 (2.38%)
occurrences all number	1	1	3
Hypoalbuminaemia
subjects affected / exposed	3 / 45 (6.67%)	0 / 17 (0.00%)	6 / 126 (4.76%)
occurrences all number	3	0	7

More information

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Were there any global substantial amendments to the protocol? Yes

19 Jun 2020

Protocol amendment v2: Determination of sample size assumptions was updated. Comparison of the objective response rate of the tiragolumab in combination with atezolizumab arm for the primary analysis was clarified. An interim analysis (IA) was added in response to feedback from the Voluntary Harmonization Procedure (VHP). The IA was performed when approximately 60 participants had been randomized to the tiragolumab in combination with atezolizumab arm and had the opportunity to be followed up for at least 5 months.

08 Jan 2021

Protocol amendment v3: Atezolizumab safety information was updated. Safety information about COVID-19 was provided. Immunosuppressive medications were removed from the prohibited therapy section and added to the cautionary therapy section to align with atezolizumab management guidelines. Language was added to clarify that AEs associated with a special situation that also qualify as adverse events of special interest (AESI) should be reported within 24 hours. Language was added to clarify that hemophagocytic lymphohistiocytosis and macrophage activation syndrome are considered potential risks for atezolizumab. A potential China extension to the study was described.

25 Mar 2021

Protocol amendment v4: The population for efficacy analyses was amended to include only randomized participants who received at least one dose of study treatment. This change enables evaluation of the efficacy of tiragolumab in combination with atezolizumab and atezolizumab monotherapy in the context of currently available therapy, in line with the use of a pre-specified reference for the primary statistical test. The primary analysis timing was amended to enable sufficient follow-up of the responders and to assess the durability of the response.

16 Feb 2022

Protocol amendment v5: A benefit-risk assessment and guidance on concomitant administration of coronavirus disease 2019 vaccines with tiragolumab and/or atezolizumab were added. The AE management guidelines were updated to align with the Atezolizumab Investigator's Brochure, v18.

22 Dec 2022

Protocol amendment v6: Various sections of the protocol were mainly amended to align with the Atezolizumab Investigator’s Brochure (Version 19) and Tiragolumab Investigator’s Brochure (Version 7).

11 Feb 2023

Protocol amendment v7: The post-trial access language was updated to state that eligible participants will have continued access to Roche IMPs (tiragolumab and/or atezolizumab) in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.

23 Oct 2023

Protocol amendment v8: Collection of information on long-term survival follow-up after treatment discontinuation was removed as it will no longer be needed, in order to reduce site burden as the protocol analysis was conducted. The pharmacokinetic, immunogenicity, and biomarker sample collection schedule was changed so that samples were no longer collected at treatment discontinuation visit or PD visit because the Sponsor decided that no additional sample collection is needed. The adverse event management guidelines were updated to align with the Atezolizumab Investigator’s Brochure, Version 20, and Tiragolumab Investigator’s Brochure, Version 7.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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