Trial Outcomes & Findings for A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck (NCT NCT04665843)
NCT ID: NCT04665843
Last Updated: 2026-05-05
Results Overview
A confirmed objective response rate (ORR) was defined as the percentage of participants with a confirmed objective response (OR), characterized by a complete response (CR) or a partial response (PR), on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as 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. Percentages have been rounded off.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
123 participants
Primary outcome timeframe
Up to approximately 30.6 months
Results posted on
2026-05-05
Participant Flow
A total of 123 participants diagnosed with recurrent/metastatic programmed death-ligand 1 (PD-L1) positive squamous cell carcinoma of the head and neck (SCCHN) took part in the study at 57 investigative sites across 13 countries from 02 March 2021 to 27 August 2025.
Participants were randomized in a 2:1 ratio to receive either tiragolumab + atezolizumab (Tira + Atezo) or placebo + atezolizumab (Pbo + Atezo). The study is considered "Completed" because all the pre-planned study activities and analyses have been performed.
Participant milestones
| Measure |
Pbo + Atezo
Participants received atezolizumab, 1200 milligrams (mg) as intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until disease progression (PD), unacceptable toxicity or loss of clinical benefit.
|
Tira + Atezo
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Overall Study
STARTED
|
41
|
82
|
|
Overall Study
Safety-evaluable (SE) Population
|
39
|
80
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
41
|
82
|
Reasons for withdrawal
| Measure |
Pbo + Atezo
Participants received atezolizumab, 1200 milligrams (mg) as intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until disease progression (PD), unacceptable toxicity or loss of clinical benefit.
|
Tira + Atezo
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Overall Study
Death
|
28
|
60
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Study Ended by Sponsor
|
10
|
11
|
|
Overall Study
Withdrawal by Subject
|
2
|
9
|
Baseline Characteristics
A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck
Baseline characteristics by cohort
| Measure |
Pbo + Atezo
n=41 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Tira + Atezo
n=82 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Total
n=123 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.7 years
STANDARD_DEVIATION 10.0 • n=54 Participants
|
64.6 years
STANDARD_DEVIATION 10.3 • n=60 Participants
|
64.3 years
STANDARD_DEVIATION 10.2 • n=114 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=54 Participants
|
17 Participants
n=60 Participants
|
28 Participants
n=114 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=54 Participants
|
65 Participants
n=60 Participants
|
95 Participants
n=114 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=54 Participants
|
3 Participants
n=60 Participants
|
3 Participants
n=114 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=54 Participants
|
60 Participants
n=60 Participants
|
89 Participants
n=114 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=54 Participants
|
19 Participants
n=60 Participants
|
31 Participants
n=114 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=54 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=54 Participants
|
19 Participants
n=60 Participants
|
27 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=54 Participants
|
0 Participants
n=60 Participants
|
1 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=54 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=54 Participants
|
43 Participants
n=60 Participants
|
63 Participants
n=114 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=54 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=114 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=54 Participants
|
20 Participants
n=60 Participants
|
32 Participants
n=114 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 30.6 monthsPopulation: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
A confirmed objective response rate (ORR) was defined as the percentage of participants with a confirmed objective response (OR), characterized by a complete response (CR) or a partial response (PR), on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as 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. Percentages have been rounded off.
Outcome measures
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Percentage of Participants With Confirmed Objective Response, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
|
21.3 percentage of participants
Interval 13.21 to 32.11
|
15.4 percentage of participants
Interval 6.41 to 31.21
|
SECONDARY outcome
Timeframe: From first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 30.6 months)Population: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. Overall number analyzed is the number of participants with a confirmed OR.
DOR was defined as the time from the first occurrence of a documented confirmed OR to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Confirmed OR was defined as either a CR or a PR on 2 consecutive occasions ≥ 4 weeks apart. CR was defined as disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Kaplan-Meier (K-M) method was used to estimate the median DOR.
Outcome measures
| Measure |
Tira + Atezo
n=17 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=6 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Duration of Response (DOR)
|
14.75 months
Interval 9.69 to
Upper limit of 95% CI was not estimable due to insufficient number of participants with events.
|
NA months
Interval 6.28 to
Median and upper limit of 95% confidence interval (CI) were not estimable due to insufficient number of participants with events.
|
SECONDARY outcome
Timeframe: From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 30.6 months)Population: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate the median PFS.
Outcome measures
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Progression-free Survival (PFS)
|
4.14 months
Interval 2.86 to 7.0
|
2.99 months
Interval 1.48 to 7.13
|
SECONDARY outcome
Timeframe: From randomization to death from any cause (up to approximately 30.6 months)Population: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
OS was defined as the time from randomization to death from any cause. K-M method was used to estimate the median OS.
Outcome measures
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Overall Survival (OS)
|
16.23 months
Interval 12.68 to 19.88
|
13.57 months
Interval 8.84 to 18.92
|
SECONDARY outcome
Timeframe: Month 6Population: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
PFS rate at 6 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at Month 6. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate the PFS rate. Percentages have been rounded off.
Outcome measures
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
PFS Rate at 6 Months
|
42.10 percentage of participants
Interval 31.07 to 53.12
|
35.90 percentage of participants
Interval 20.84 to 50.95
|
SECONDARY outcome
Timeframe: Months 6 and 12Population: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
OS rate at 6 months and 12 months was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off.
Outcome measures
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
OS Rate at 6 Months and 12 Months
Month 6
|
83.37 percentage of participants
Interval 75.11 to 91.63
|
76.92 percentage of participants
Interval 63.7 to 90.15
|
|
OS Rate at 6 Months and 12 Months
Month 12
|
64.84 percentage of participants
Interval 54.14 to 75.55
|
53.05 percentage of participants
Interval 37.21 to 68.89
|
SECONDARY outcome
Timeframe: Up to approximately 30.6 monthsPopulation: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
TTCD=time from the date of randomization to the first confirmed clinically meaningful deterioration (CCMD). PROMIS Item Bank v2.0-PF- Short Form 10b is a 10-item participant-reported questionnaire including 2 types of items to assess PF: 6 ability-based items assessing difficulty in performing activities, scored on a 5-point scale ranging from 1=Unable to do, 2=With much difficulty, 3=With some difficulty, 4=With a little difficulty, 5=Without any difficulty; and 4 limitation-based items assessing the extent to which health limits activities, scored on a 5-point scale ranging from 1=Cannot do, 2=Quite a lot, 3=Somewhat, 4=Very little, 5=Not at all. Item responses were summed to generate a raw score and converted to a PROMIS T-score, with a higher T-score indicating better PF. CCMD=decrease from baseline (≥ 4 points) in T-score, held for at least 2 consecutive assessments. K-M method was used to estimate median TTCD.
Outcome measures
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Time to Confirmed Deterioration (TTCD) in Participant-reported Physical Functioning (PF), as Measured by the Patient-reported Outcomes Measurement Information System (PROMIS) Item Bank Version 2.0 (v2.0)-PF-Short Form 10b
|
11.76 months
Interval 6.24 to
Upper limit of 95% CI was not estimable due to insufficient number of participants with events.
|
9.00 months
Interval 3.84 to
Upper limit of 95% CI was not estimable due to insufficient number of participants with events.
|
SECONDARY outcome
Timeframe: From study start up to 90 days after last dose (up to approximately 52.9 months)Population: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received.
An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any of the following: 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
| Measure |
Tira + Atezo
n=80 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=39 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
|
76 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/early discontinuation (ED) (1 Cycle=21 days) (up to approximately 49.9 months)Population: Atezolizumab pharmacokinetic (PK)-evaluable population included all randomized participants who received at least one dose of atezolizumab and had atleast 1 evaluable PK sample. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
Outcome measures
| Measure |
Tira + Atezo
n=79 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=38 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 16
|
284 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 46.4
|
170 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 21.4
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Treatment Completion/ED
|
137 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 58.9
|
82.8 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 105.3
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 1
|
NA micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation NA
GM and Geometric Coefficient of Variation were not estimable because the values were below the level of detection.
|
NA micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation NA
Geometric Mean (GM) and Geometric Coefficient of Variation were not estimable because the values were below the level of detection.
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
30 minutes post-dose, Day 1 of Cycle 1
|
285 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 296.9
|
262 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 340.5
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 2
|
84.3 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 44.0
|
80.4 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 40.5
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 3
|
132 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 41.5
|
118 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 37.0
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 4
|
164 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 41.3
|
131 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 44.7
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 8
|
186 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 63.2
|
197 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 41.3
|
|
Serum Concentration of Atezolizumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 12
|
215 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 59.7
|
218 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 38.9
|
SECONDARY outcome
Timeframe: Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/ED (1 Cycle=21 days) (up to approximately 49.9 months)Population: Tiragolumab PK-evaluable population included all randomized participants who received at least one dose of tiragolumab. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
Outcome measures
| Measure |
Tira + Atezo
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=74 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 1
|
—
|
NA µg/mL
Geometric Coefficient of Variation NA
GM and Geometric Coefficient of Variation were not estimable because the values were below the level of detection.
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
30 minutes post-dose, Day 1 of Cycle 1
|
—
|
147 µg/mL
Geometric Coefficient of Variation 863.7
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 2
|
—
|
44.6 µg/mL
Geometric Coefficient of Variation 45.9
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 3
|
—
|
65.7 µg/mL
Geometric Coefficient of Variation 46.9
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 4
|
—
|
80.2 µg/mL
Geometric Coefficient of Variation 45.5
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 8
|
—
|
89.8 µg/mL
Geometric Coefficient of Variation 77.8
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 12
|
—
|
104 µg/mL
Geometric Coefficient of Variation 49.6
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Pre-dose, Day 1 of Cycle 16
|
—
|
124 µg/mL
Geometric Coefficient of Variation 40.5
|
|
Serum Concentration of Tiragolumab at Specified Timepoints
Treatment Completion/ED
|
—
|
67.5 µg/mL
Geometric Coefficient of Variation 53.6
|
SECONDARY outcome
Timeframe: Up to approximately 49.9 monthsPopulation: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. Overall number analyzed is the number of participants with data available for analysis.
Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following atezolizumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 0.60 titer unit (t.u.) greater than the baseline titer result (treatment-enhanced ADA response).
Outcome measures
| Measure |
Tira + Atezo
n=74 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=34 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Number of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
|
11 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 49.9 monthsPopulation: SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. Overall number analyzed is the number of participants with data available for analysis.
Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following tiragolumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 0.60 t.u. greater than the baseline titer result (treatment-enhanced ADA response).
Outcome measures
| Measure |
Tira + Atezo
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Pbo + Atezo
n=74 Participants
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Number of Participants With ADAs to Tiragolumab
|
—
|
0 Participants
|
Adverse Events
Pbo + Atezo
Serious events: 14 serious events
Other events: 28 other events
Deaths: 28 deaths
Tira + Atezo
Serious events: 23 serious events
Other events: 68 other events
Deaths: 62 deaths
Serious adverse events
| Measure |
Pbo + Atezo
n=39 participants at risk
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Tira + Atezo
n=80 participants at risk
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Crohn's disease
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Large intestine perforation
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Oesophageal fistula
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Asthenia
|
2.6%
1/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Death
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
2.5%
2/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Device related thrombosis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
General physical health deterioration
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Pyrexia
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Hepatobiliary disorders
Hepatic cytolysis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Hepatobiliary disorders
Immune-mediated hepatic disorder
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
Pneumonia
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
3.8%
3/80 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
Pneumonia aspiration
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
Sepsis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
Stoma site infection
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
Wound infection
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Investigations
Lymphocyte count decreased
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
2.5%
2/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Nervous system disorders
Syncope
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Immune-mediated lung disease
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Vascular disorders
Hypotension
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Vascular disorders
Jugular vein thrombosis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Vascular disorders
Shock haemorrhagic
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Type 1 diabetes mellitus
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Spinal stenosis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Nervous system disorders
Carotid artery stenosis
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Dermatitis psoriasiform
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Pemphigoid
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
Other adverse events
| Measure |
Pbo + Atezo
n=39 participants at risk
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by placebo also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
Tira + Atezo
n=80 participants at risk
Participants received atezolizumab, 1200 mg as IV infusion, Q3W on Day 1 of each 21-day cycle, followed by tiragolumab, 600 mg also administered as IV infusion, Q3W on Day 1 of each 21-day cycle until PD, unacceptable toxicity or loss of clinical benefit.
|
|---|---|---|
|
Gastrointestinal disorders
Dry mouth
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Dysphagia
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
7.5%
6/80 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Nausea
|
12.8%
5/39 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
10.0%
8/80 • Number of events 10 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
3/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
10.0%
8/80 • Number of events 10 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Blood and lymphatic system disorders
Anaemia
|
10.3%
4/39 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
12.5%
10/80 • Number of events 11 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
3.8%
3/80 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Endocrine disorders
Hyperthyroidism
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
7.5%
6/80 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Endocrine disorders
Hypothyroidism
|
15.4%
6/39 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
18.8%
15/80 • Number of events 16 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Breath odour
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Constipation
|
20.5%
8/39 • Number of events 8 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
11.2%
9/80 • Number of events 9 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Stomatitis
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
3.8%
3/80 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
6.2%
5/80 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Asthenia
|
17.9%
7/39 • Number of events 9 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
12.5%
10/80 • Number of events 12 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Fatigue
|
12.8%
5/39 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
13.8%
11/80 • Number of events 13 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Oedema peripheral
|
7.7%
3/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
2.5%
2/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
General disorders
Pyrexia
|
10.3%
4/39 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
5.0%
4/80 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
COVID-19
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
5.0%
4/80 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Infections and infestations
Conjunctivitis
|
5.1%
2/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
5.1%
2/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
5.0%
4/80 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Investigations
Weight decreased
|
10.3%
4/39 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
11.2%
9/80 • Number of events 9 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.4%
6/39 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
15.0%
12/80 • Number of events 13 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Dehydration
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
7.7%
3/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.3%
4/39 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.1%
2/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
2.5%
2/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
8.8%
7/80 • Number of events 8 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
3/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
2.5%
2/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.3%
4/39 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
5.0%
4/80 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.7%
3/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
6.2%
5/80 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Nervous system disorders
Headache
|
7.7%
3/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
7.5%
6/80 • Number of events 7 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Psychiatric disorders
Depression
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
6.2%
5/80 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Psychiatric disorders
Insomnia
|
5.1%
2/39 • Number of events 3 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
6.2%
5/80 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.3%
4/39 • Number of events 4 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
12.5%
10/80 • Number of events 12 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.8%
5/39 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
8.8%
7/80 • Number of events 7 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
7.7%
3/39 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
1.2%
1/80 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.6%
1/39 • Number of events 1 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
11.2%
9/80 • Number of events 9 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
8.8%
7/80 • Number of events 8 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.1%
2/39 • Number of events 6 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
23.8%
19/80 • Number of events 23 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.6%
1/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
11.2%
9/80 • Number of events 12 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/39 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
6.2%
5/80 • Number of events 7 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
0.00%
0/80 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
|
Vascular disorders
Hypertension
|
5.1%
2/39 • Number of events 2 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
3.8%
3/80 • Number of events 5 • All AEs: From study start up to 90 days after last dose (up to approximately 52.9 months) All-cause mortality: Up to 53.8 months
SE population included all randomized participants who received at least one dose of study treatment, with participants grouped and analyzed based on actual treatment received. 4 participants did not receive any study treatment and were therefore excluded from safety analysis.
|
Additional Information
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