Trial Outcomes & Findings for A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2) (NCT NCT02108652)

Last Updated: 2024-03-28

Results Overview

Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

310 participants

Primary outcome timeframe

Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Results posted on

2024-03-28

Participant Flow

The study is considered "Completed" because the planned study activities and analyses have been performed.

The analysis included data up to cutoff date 28 February 2023.

Participant milestones

Participant milestones
Measure	Cohort 2: Participants With Second-line or Beyond Treatments Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Study STARTED	310
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	310

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 2: Participants With Second-line or Beyond Treatments Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Study Death	253
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	16
Overall Study Study Terminated By Sponsor	31
Overall Study Non-Compliance	1
Overall Study Physician Decision	6
Overall Study Progression Of Disease	1

Baseline Characteristics

A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Age, Continuous	65.6 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants
Sex: Female, Male Male	241 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Population: Cohort 2 objective response-evaluable population included Intent-to-treat (ITT) participants who had measurable disease per RECIST v1.1 at baseline. Cohort 2 ITT population included all participants from Cohort 2 who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	15.8 percentage of participants Interval 11.9 to 20.4

PRIMARY outcome

Population: Cohort 2 objective response-evaluable population.

Tumor response was assessed by the investigator according to modified RECIST. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According Modified RECIST	19.7 percentage of participants Interval 15.4 to 24.6

SECONDARY outcome

Population: Cohort 2 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=49 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1	NA months Interval 2.1 to The median DOR and upper limit for the Full Range were not reached at a median follow up of 21.060 months on study.

SECONDARY outcome

Population: Cohort 2 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=51 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
DOR as Assessed by the Investigator According to RECIST v1.1	20.50 months Interval 2.1 to 20.5

SECONDARY outcome

Population: Cohort 2 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the investigator according to modified RECIST. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=61 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
DOR as Assessed by the Investigator According to Modified RECIST	20.50 months Interval 2.1 to 20.5

SECONDARY outcome

Population: Cohort 2 ITT population

Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1	88.4 percentage of participants

SECONDARY outcome

Population: Cohort 2 ITT population

PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1	2.10 months Interval 2.07 to 2.14

SECONDARY outcome

Population: Cohort 2 ITT population

Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1	89.7 percentage of participants

SECONDARY outcome

Population: Cohort 2 ITT population

PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
PFS as Assessed by the Investigator According to RECIST v1.1	2.10 months Interval 2.07 to 2.14

SECONDARY outcome

Population: Cohort 2 ITT population

Tumor response was assessed by the investigator according to modified RECIST. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to Modified RECIST	87.1 percentage of participants

SECONDARY outcome

Population: Cohort 2 ITT population

PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the investigator according to modified RECIST. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
PFS as Assessed by the Investigator According to Modified RECIST	2.56 months Interval 2.14 to 3.61

SECONDARY outcome

Population: Cohort 2 objective response-evaluable population.

Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1	16.5 percentage of participants Interval 12.5 to 21.1

SECONDARY outcome

Timeframe: Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Population: Cohort 2 ITT population

The percentage of participants who died from any cause was reported.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants Who Died	72.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Population: Cohort 2 ITT population

OS was defined as the time from start of treatment to the time of death from any cause on study.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Survival (OS)	7.9 months Interval 6.7 to 9.3

SECONDARY outcome

Timeframe: 1-year

Population: Cohort 2 ITT Population

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=310 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants Alive at 1-year	36.9 percentage of participants Interval 31.4 to 42.3

SECONDARY outcome

Timeframe: Pre-dose (0 hours) and 30 minutes post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)

Population: Cohort 2 pharmacokinetic (PK) evaluable population was defined as participants who received any dose of atezolizumab treatment and had PK data at timepoints that were sufficient to determine PK parameters. Here, number of participants analyzed = participants who were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=300 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Maximum Serum Concentration (Cmax) of Atezolizumab	364 microgram(s)/milliliter (mcg/mL) Standard Deviation 120

SECONDARY outcome

Timeframe: Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)

Population: Cohort 2 PK evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome. "n" = participants who were evaluable at specified timepoint.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=303 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Minimum Serum Concentration (Cmin) of Atezolizumab Pre-dose Cycle 1 (n=303)	0.0252 mcg/mL Standard Deviation 0.429
Minimum Serum Concentration (Cmin) of Atezolizumab Pre-dose Cycle 2 (n=269)	74.2 mcg/mL Standard Deviation 29.9
Minimum Serum Concentration (Cmin) of Atezolizumab Pre-dose Cycle 4 (n=186)	147.0 mcg/mL Standard Deviation 77.7
Minimum Serum Concentration (Cmin) of Atezolizumab Pre-dose Cycle 8 (n=108)	188.0 mcg/mL Standard Deviation 76.1
Minimum Serum Concentration (Cmin) of Atezolizumab Pre-dose Cycle 3 (n=146)	120.0 mcg/mL Standard Deviation 59.5

SECONDARY outcome

Timeframe: Day 1 of all cycles (Cycle length = 21 days) and at treatment discontinuation (data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Population: Cohort 2 Safety Evaluable Population. Here, number of participants analyzed = participants for whom ATA samples were available.

Outcome measures

Outcome measures
Measure	Cohort 2: Participants With Second-line or Beyond Treatments n=276 Participants Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab	42.4 percentage of participants

Adverse Events

MPDL3280A COHORT2 INFUSION

Serious events: 155 serious events

Other events: 287 other events

Deaths: 253 deaths

Serious adverse events

Serious adverse events
Measure	MPDL3280A COHORT2 INFUSION n=310 participants at risk
Blood and lymphatic system disorders ANAEMIA	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Blood and lymphatic system disorders LEUKOCYTOSIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Blood and lymphatic system disorders LYMPH NODE PAIN	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders ARRHYTHMIA	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders ATRIAL FIBRILLATION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders CARDIAC ARREST	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders CARDIAC FAILURE	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders CORONARY ARTERY DISEASE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Cardiac disorders PERICARDIAL EFFUSION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Ear and labyrinth disorders VERTIGO	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Endocrine disorders HYPOTHYROIDISM	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders ABDOMINAL HERNIA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders ABDOMINAL PAIN	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders ANAL INCONTINENCE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders AUTOIMMUNE COLITIS	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders COLITIS	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders COLITIS ISCHAEMIC	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders DIARRHOEA	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders ILEUS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders INTESTINAL OBSTRUCTION	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders INTESTINAL PERFORATION	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders LARGE INTESTINAL OBSTRUCTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders NAUSEA	0.97% 3/310 • Number of events 4 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders RECTAL HAEMORRHAGE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	1.9% 6/310 • Number of events 9 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders SUBILEUS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders VOMITING	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders ASTHENIA	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders CHILLS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders FATIGUE	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders GAIT DISTURBANCE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders HAEMORRHAGIC CYST	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders MALAISE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders NON-CARDIAC CHEST PAIN	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders PAIN	1.3% 4/310 • Number of events 6 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders PERFORMANCE STATUS DECREASED	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders PYREXIA	2.6% 8/310 • Number of events 8 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Hepatobiliary disorders CHOLECYSTITIS	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Hepatobiliary disorders HEPATITIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Hepatobiliary disorders HYPERBILIRUBINAEMIA	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Hepatobiliary disorders LIVER DISORDER	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Immune system disorders HYPERSENSITIVITY	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations ABDOMINAL INFECTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations BACTERAEMIA	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations BILIARY SEPSIS	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations BRONCHITIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations BURSITIS INFECTIVE STAPHYLOCOCCAL	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations CELLULITIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations CELLULITIS OF MALE EXTERNAL GENITAL ORGAN	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations DEVICE RELATED INFECTION	0.32% 1/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations DIVERTICULITIS	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations GASTROENTERITIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations INFLUENZA	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations KIDNEY INFECTION	0.65% 2/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations MENINGOENCEPHALITIS HERPETIC	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations PNEUMONIA	2.3% 7/310 • Number of events 7 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations POST PROCEDURAL INFECTION	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations PULMONARY SEPSIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations PYELONEPHRITIS	1.3% 4/310 • Number of events 4 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations RETROPERITONEAL INFECTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations SEPSIS	2.9% 9/310 • Number of events 9 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations SKIN INFECTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations STAPHYLOCOCCAL INFECTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations URINARY TRACT INFECTION	7.4% 23/310 • Number of events 24 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations URINARY TRACT INFECTION PSEUDOMONAL	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations UROSEPSIS	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations VASCULAR DEVICE INFECTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications FALL	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications FRACTURE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications HIP FRACTURE	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications ILIUM FRACTURE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications JOINT INJURY	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications POST PROCEDURAL HAEMORRHAGE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications SPINAL COMPRESSION FRACTURE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications STOMA SITE HAEMORRHAGE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications TOXICITY TO VARIOUS AGENTS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Injury, poisoning and procedural complications VASCULAR PSEUDOANEURYSM RUPTURED	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations BLOOD BILIRUBIN INCREASED	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations BLOOD CREATINE PHOSPHOKINASE INCREASED	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations BLOOD CREATININE INCREASED	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations PLATELET COUNT DECREASED	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations WHITE BLOOD CELL COUNT DECREASED	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders DEHYDRATION	1.9% 6/310 • Number of events 6 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders FAILURE TO THRIVE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPERCALCAEMIA	1.3% 4/310 • Number of events 5 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPERKALAEMIA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPONATRAEMIA	1.6% 5/310 • Number of events 5 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders BACK PAIN	1.9% 6/310 • Number of events 10 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders BONE PAIN	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders FLANK PAIN	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders OSTEOPOROSIS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders PATHOLOGICAL FRACTURE	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders RHABDOMYOLYSIS	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ADENOCARCINOMA PANCREAS	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR ASSOCIATED FEVER	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders ATAXIA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders CEREBRAL HAEMORRHAGE	0.32% 1/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders DIPLEGIA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders ENCEPHALOPATHY	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders PARAPLEGIA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders SYNCOPE	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Product Issues THROMBOSIS IN DEVICE	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Psychiatric disorders CONFUSIONAL STATE	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Psychiatric disorders DELIRIUM	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Psychiatric disorders HALLUCINATION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Psychiatric disorders MENTAL STATUS CHANGES	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders ACUTE KIDNEY INJURY	1.9% 6/310 • Number of events 6 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders BLADDER PERFORATION	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders CHRONIC KIDNEY DISEASE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders HAEMATURIA	3.9% 12/310 • Number of events 12 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders HYDRONEPHROSIS	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders HYDROURETER	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders RENAL FAILURE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders URETERIC OBSTRUCTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders URINARY RETENTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders URINARY TRACT OBSTRUCTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Reproductive system and breast disorders PELVIC PAIN	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Reproductive system and breast disorders PENILE PAIN	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Reproductive system and breast disorders VAGINAL HAEMORRHAGE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	3.2% 10/310 • Number of events 12 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders HICCUPS	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.65% 2/310 • Number of events 2 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	1.6% 5/310 • Number of events 5 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders PULMONARY ARTERY THROMBOSIS	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	2.6% 8/310 • Number of events 8 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders RESPIRATORY DISTRESS	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Skin and subcutaneous tissue disorders DERMATITIS PSORIASIFORM	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Skin and subcutaneous tissue disorders ERYTHEMA	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Skin and subcutaneous tissue disorders RASH MACULO-PAPULAR	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Social circumstances IMMOBILE	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Surgical and medical procedures RENAL STONE REMOVAL	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Surgical and medical procedures URETERAL STENT INSERTION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Vascular disorders DEEP VEIN THROMBOSIS	0.97% 3/310 • Number of events 3 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Vascular disorders EMBOLISM	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Vascular disorders HAEMATOMA	0.00% 0/310 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Vascular disorders HYPOTENSION	0.32% 1/310 • Number of events 1 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.

Other adverse events

Other adverse events
Measure	MPDL3280A COHORT2 INFUSION n=310 participants at risk
Blood and lymphatic system disorders ANAEMIA	18.1% 56/310 • Number of events 72 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders ABDOMINAL PAIN	14.2% 44/310 • Number of events 54 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders CONSTIPATION	27.4% 85/310 • Number of events 102 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders DIARRHOEA	22.3% 69/310 • Number of events 103 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders DRY MOUTH	7.7% 24/310 • Number of events 25 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders NAUSEA	27.7% 86/310 • Number of events 114 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Gastrointestinal disorders VOMITING	19.7% 61/310 • Number of events 83 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders ASTHENIA	7.4% 23/310 • Number of events 37 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders CHILLS	11.0% 34/310 • Number of events 37 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders FATIGUE	52.9% 164/310 • Number of events 228 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders INFLUENZA LIKE ILLNESS	5.5% 17/310 • Number of events 65 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders OEDEMA PERIPHERAL	16.8% 52/310 • Number of events 63 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders PAIN	8.7% 27/310 • Number of events 34 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
General disorders PYREXIA	22.6% 70/310 • Number of events 90 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations NASOPHARYNGITIS	6.1% 19/310 • Number of events 25 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	7.4% 23/310 • Number of events 28 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Infections and infestations URINARY TRACT INFECTION	20.0% 62/310 • Number of events 94 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations ALANINE AMINOTRANSFERASE INCREASED	5.2% 16/310 • Number of events 24 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	6.1% 19/310 • Number of events 20 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations BLOOD CREATININE INCREASED	7.1% 22/310 • Number of events 38 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Investigations WEIGHT DECREASED	9.0% 28/310 • Number of events 34 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders DECREASED APPETITE	28.7% 89/310 • Number of events 110 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPERGLYCAEMIA	5.5% 17/310 • Number of events 30 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPOALBUMINAEMIA	6.5% 20/310 • Number of events 26 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPOKALAEMIA	6.1% 19/310 • Number of events 24 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	5.2% 16/310 • Number of events 18 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Metabolism and nutrition disorders HYPONATRAEMIA	6.5% 20/310 • Number of events 25 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders ARTHRALGIA	21.0% 65/310 • Number of events 98 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders BACK PAIN	18.4% 57/310 • Number of events 83 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders FLANK PAIN	7.4% 23/310 • Number of events 30 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	10.0% 31/310 • Number of events 44 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders MYALGIA	5.5% 17/310 • Number of events 20 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	12.9% 40/310 • Number of events 55 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders DIZZINESS	8.4% 26/310 • Number of events 29 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Nervous system disorders HEADACHE	9.7% 30/310 • Number of events 37 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Psychiatric disorders ANXIETY	5.8% 18/310 • Number of events 18 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Psychiatric disorders INSOMNIA	7.1% 22/310 • Number of events 22 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Renal and urinary disorders HAEMATURIA	15.8% 49/310 • Number of events 76 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders COUGH	19.0% 59/310 • Number of events 86 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	17.7% 55/310 • Number of events 74 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	6.8% 21/310 • Number of events 22 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Skin and subcutaneous tissue disorders DRY SKIN	6.5% 20/310 • Number of events 21 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Skin and subcutaneous tissue disorders PRURITUS	17.4% 54/310 • Number of events 77 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Skin and subcutaneous tissue disorders RASH	12.9% 40/310 • Number of events 53 • First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months) All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER