Trial Outcomes & Findings for A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer (NCT NCT04677504)

NCT ID: NCT04677504

Last Updated: 2024-07-03

Results Overview

PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 162 participants
• Primary outcome timeframe: Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)
• Results posted on: 2024-07-03

Participant Flow

The study is considered "Completed" because all pre-planned study activities and analyses have been performed. Participants are ongoing treatment on a roll over study.

Participant milestones

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Overall Study STARTED	83	79
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	83	79

Reasons for withdrawal

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Overall Study Death	51	49
Overall Study Progressive Disease	1	0
Overall Study Symptomatic Deterioration	1	0
Overall Study Withdrawal by Subject	2	5
Overall Study Study Terminated By Sponsor	28	24
Overall Study Adverse Event	0	1

Baseline Characteristics

A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer

Baseline characteristics by cohort

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=83 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=79 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Total n=162 Participants Total of all reporting groups
Age, Continuous	63.0 Years STANDARD_DEVIATION 9.8 • n=5 Participants	59.6 Years STANDARD_DEVIATION 9.9 • n=7 Participants	61.3 Years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	30 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	49 Participants n=7 Participants	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	82 Participants n=5 Participants	78 Participants n=7 Participants	160 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	35 Participants n=5 Participants	37 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	41 Participants n=7 Participants	87 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)

Population: Analysis was performed on the Intent-to-treat (ITT) population, defined as all randomized participants, regardless of whether they received the assigned treatment or not, were included for analyses with participants grouped according to the treatment assigned at randomization.

PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=83 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=79 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Progression Free Survival (PFS)	7.92 Months Interval 6.18 to 8.41	8.35 Months Interval 6.83 to 9.96

SECONDARY outcome

Timeframe: Randomization to death from any cause (up to approximately 23 months)

Population: Analysis was performed on the Intent-to-treat (ITT) population, defined as all randomized participants, regardless of whether they received the assigned treatment or not, were included for analyses with participants grouped according to the treatment assigned at randomization.

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

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=83 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=79 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Overall Survival (OS)	14.59 Months Interval 11.17 to With \~60% events to patients ratio, this happens due to no events occurred at the timepoint in the upper end required per the non-parameteric estimation method of Brookmeyer-Crowley.	14.85 Months Interval 11.63 to 17.97

SECONDARY outcome

Timeframe: Randomization up to approximately 14 months

Population: Analysis was performed on the Intent-to-treat (ITT) population, defined as all randomized participants, regardless of whether they received the assigned treatment or not, were included for analyses with participants grouped according to the treatment assigned at randomization.

Confirmed ORR is defined as the proportion of participants with Complete Response (CR) or Partial Response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=83 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=79 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Confirmed Objective Response Rate (ORR)	25.3 Percentage of participants	24.1 Percentage of participants

SECONDARY outcome

Timeframe: First occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)

Population: Analysis was performed on the Intent-to-treat (ITT) population, defined as all randomized participants, regardless of whether they received the assigned treatment or not, were included for analyses with participants grouped according to the treatment assigned at randomization.

DOR is defined as the time from the first occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first).

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=21 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=19 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Duration of Response (DOR)	5.78 Months Interval 4.27 to 6.7	NA Months Interval 6.44 to Insufficient number of participants with events.

SECONDARY outcome

Timeframe: Randomization up to approximately 14 months

Population: Analysis was performed on the Intent-to-treat (ITT) population, defined as all randomized participants, regardless of whether they received the assigned treatment or not, were included for analyses with participants grouped according to the treatment assigned at randomization.

DCR is defined as the proportion of participants with a CR or a PR on two consecutive occasions >= 4 weeks apart or SD with a minimum duration of 9weeks, as determined by the investigator according to RECIST v1.1

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=83 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=79 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Disease Control Rate (DCR)	75.9 Percentage of participants	78.5 Percentage of participants

SECONDARY outcome

Timeframe: Randomization to the first clinically meaningful deterioration (up to approximately 14 months)

Population: Analysis was performed on the Intent-to-treat (ITT) population, defined as all randomized participants, regardless of whether they received the assigned treatment or not, were included for analyses with participants grouped according to the treatment assigned at randomization.

TTCD in patient-reported physical functioning, role functioning, and quality of life, as measured by the respective scales of the EORTC QLQ-C30 and/or EORTC IL77, and defined as the time from randomization to the first clinically meaningful deterioration that is either maintained for two consecutive assessments or followed by death from any cause within 3 weeks.

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=83 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=79 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Time to Confirmed Deterioration (TTCD) Quality of Life	6.28 Months Interval 3.06 to Insufficient number of participants with events.	2.79 Months Interval 1.58 to 5.32
Time to Confirmed Deterioration (TTCD) Physical Function Scale	3.29 Months Interval 1.87 to 10.58	6.21 Months Interval 4.63 to Insufficient number of participants with events.
Time to Confirmed Deterioration (TTCD) Role Function Scale	3.52 Months Interval 2.2 to 8.51	4.24 Months Interval 2.1 to 6.28

SECONDARY outcome

Timeframe: Treatment start up to approximately 30 months.

Population: Safety analyses will be performed on the safety-evaluable population, which is defined as all randomized participants who receive any amount of any component of protocol treatment.

Percentage of participants with at least one adverse event.

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=81 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=78 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Percentage of Participants With at Least One Adverse Event	100 Percentage of participants	100 Percentage of participants

SECONDARY outcome

Timeframe: Pre-Dose on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and Post Dose Day 1 of Cycle 1 (cycle length=21 days)

Population: The PK analysis population consisted of all participants with at least 1 PK assessment.

Serum concentration of atezolizumab at specified timepoints.

Outcome measures

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=78 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=81 Participants \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Serum Concentration of Atezolizumab Cycle 1 Day 1 Pre-Dose	NA μg/ mL Standard Deviation NA Below the level of detection.	NA μg/ mL Standard Deviation NA Below the level of detection.
Serum Concentration of Atezolizumab Cycle 1 Day 1 Post Dose	411 μg/ mL Standard Deviation 73.8	416 μg/ mL Standard Deviation 173
Serum Concentration of Atezolizumab Cycle 2 Day 1 Pre-Dose	79.4 μg/ mL Standard Deviation 46.1	85.0 μg/ mL Standard Deviation 71.7
Serum Concentration of Atezolizumab Cycle 3 Day 1 Pre-Dose	118 μg/ mL Standard Deviation 41.4	129 μg/ mL Standard Deviation 83.5
Serum Concentration of Atezolizumab Cycle 4 Day 1 Pre-Dose	155 μg/ mL Standard Deviation 50.6	153 μg/ mL Standard Deviation 74.8
Serum Concentration of Atezolizumab Cycle 8 Day 1 Pre-Dose	200 μg/ mL Standard Deviation 100	224 μg/ mL Standard Deviation 126
Serum Concentration of Atezolizumab Cycle 12 Day 1 Pre-Dose	210 μg/ mL Standard Deviation 76.4	223 μg/ mL Standard Deviation 103
Serum Concentration of Atezolizumab Cycle 16 Day 1 Pre-Dose	174 μg/ mL Standard Deviation 64.9	230 μg/ mL Standard Deviation 71.6

SECONDARY outcome

Timeframe: Baseline

Population: The immunogenicity analysis population consist of all participants with at least 1 postbaseline ADA assessment. Participants are grouped according to treatment received. No data were collected because the study was discontinued before any measurements were completed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At pre-defined intervals from administration of study drug up to approximately 14 months

Population: The immunogenicity analysis population consist of all participants with at least 1 postbaseline ADA assessment. Participants are grouped according to treatment received. No data were collected because the study was discontinued before any measurements were completed.

Outcome measures

Outcome data not reported

Adverse Events

Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond)

Serious events: 43 serious events

Other events: 81 other events

Deaths: 51 deaths

Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond)

Serious events: 36 serious events

Other events: 77 other events

Deaths: 49 deaths

Serious adverse events

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=81 participants at risk \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=78 participants at risk \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
General disorders Fatigue	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Blood and lymphatic system disorders Anaemia	7.4% 6/81 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Blood and lymphatic system disorders Neutropenia	2.5% 2/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Blood and lymphatic system disorders Thrombocytopenia	2.5% 2/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Cardiac disorders Cardiac failure acute	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Abdominal pain	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Abdominal pain upper	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Colitis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Diarrhoea	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Duodenal perforation	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Duodenal ulcer	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Enterocolitis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Gastrointestinal obstruction	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Haematemesis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Intestinal perforation	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Large intestinal stenosis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Nausea	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Pancreatitis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Asthenia	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Death	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Oedema peripheral	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Pyrexia	6.2% 5/81 • Number of events 10 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	3.8% 3/78 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Biliary dilatation	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Biliary obstruction	3.7% 3/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Cholangitis	6.2% 5/81 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Cholestasis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Hepatitis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Hepatobiliary disease	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Jaundice	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Jaundice cholestatic	3.7% 3/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Anal abscess	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Appendicitis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Bacteraemia	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Biliary tract infection	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Cystitis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Diverticulitis	1.2% 1/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Enterocolitis infectious	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Infection	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Liver abscess	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Peritonitis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Pneumonia	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Recurrent pyogenic cholangitis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Sepsis	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Septic shock	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Urinary tract infection	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Injury, poisoning and procedural complications Head injury	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Injury, poisoning and procedural complications Spinal compression fracture	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Alanine aminotransferase increased	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Aspartate aminotransferase increased	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Blood bilirubin increased	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Blood culture positive	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Platelet count decreased	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations White blood cell count decreased	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Diabetes mellitus	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hypocalcaemia	1.2% 1/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hypokalaemia	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Musculoskeletal and connective tissue disorders Back pain	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Musculoskeletal and connective tissue disorders Bone pain	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Brain stem infarction	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Cerebellar infarction	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Cerebrovascular accident	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Transient ischaemic attack	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Psychiatric disorders Confusional state	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Renal and urinary disorders Acute kidney injury	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	3.8% 3/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Renal and urinary disorders Nephropathy toxic	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Reproductive system and breast disorders Prostatic obstruction	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	2.6% 2/78 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Vascular disorders Extremity necrosis	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Vascular disorders Hypertension	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Vascular disorders Hypotension	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Vascular disorders Thrombosis	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Eye disorders Ocular myasthenia	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Haematochezia	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Sudden death	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Ulcer haemorrhage	1.2% 1/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Gallbladder obstruction	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Hepatobiliary disorders Hepatotoxicity	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Haematological infection	1.2% 1/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Klebsiella bacteraemia	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Blood creatinine increased	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Cerebral infarction	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	0.00% 0/78 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.

Other adverse events

Measure	Arm B: Atezo+PBO+CisGem (Cycle*1-8), Followed by Atezo+PBO (Cycle*9 and Beyond) n=81 participants at risk \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.	Arm A: Atezo+Bev+CisGem (Cycle*1-8), Followed by Atezo+Bev (Cycle*9 and Beyond) n=78 participants at risk \*Cycle is 21 days. Cisplatin is administered on Days 1 and 8 of each 21 day cycle for cycles 1-8.
Blood and lymphatic system disorders Anaemia	63.0% 51/81 • Number of events 88 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	47.4% 37/78 • Number of events 59 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Blood and lymphatic system disorders Neutropenia	21.0% 17/81 • Number of events 31 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	21.8% 17/78 • Number of events 37 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Blood and lymphatic system disorders Thrombocytopenia	7.4% 6/81 • Number of events 13 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	9.0% 7/78 • Number of events 18 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Endocrine disorders Hypothyroidism	7.4% 6/81 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	7.7% 6/78 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Abdominal pain	16.0% 13/81 • Number of events 16 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	19.2% 15/78 • Number of events 16 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Ascites	6.2% 5/81 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	6.4% 5/78 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Constipation	28.4% 23/81 • Number of events 25 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	38.5% 30/78 • Number of events 39 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Diarrhoea	16.0% 13/81 • Number of events 16 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	17.9% 14/78 • Number of events 22 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Dyspepsia	8.6% 7/81 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	3.8% 3/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Haemorrhoids	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Nausea	39.5% 32/81 • Number of events 44 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	41.0% 32/78 • Number of events 51 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Stomatitis	6.2% 5/81 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	12.8% 10/78 • Number of events 10 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Vomiting	14.8% 12/81 • Number of events 12 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	20.5% 16/78 • Number of events 23 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Asthenia	19.8% 16/81 • Number of events 33 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	17.9% 14/78 • Number of events 28 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Fatigue	22.2% 18/81 • Number of events 22 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	26.9% 21/78 • Number of events 29 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Oedema peripheral	8.6% 7/81 • Number of events 8 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	7.7% 6/78 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Pyrexia	24.7% 20/81 • Number of events 44 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	17.9% 14/78 • Number of events 26 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations COVID-19	16.0% 13/81 • Number of events 13 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	14.1% 11/78 • Number of events 12 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Infections and infestations Urinary tract infection	8.6% 7/81 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Alanine aminotransferase increased	18.5% 15/81 • Number of events 22 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	14.1% 11/78 • Number of events 15 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Aspartate aminotransferase increased	21.0% 17/81 • Number of events 20 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	12.8% 10/78 • Number of events 15 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Blood alkaline phosphatase increased	6.2% 5/81 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	6.4% 5/78 • Number of events 9 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Blood bilirubin increased	8.6% 7/81 • Number of events 11 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	10.3% 8/78 • Number of events 8 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Blood creatinine increased	13.6% 11/81 • Number of events 13 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	9.0% 7/78 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Lymphocyte count decreased	8.6% 7/81 • Number of events 19 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	9.0% 7/78 • Number of events 17 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Neutrophil count decreased	39.5% 32/81 • Number of events 80 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	48.7% 38/78 • Number of events 93 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Platelet count decreased	27.2% 22/81 • Number of events 49 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	28.2% 22/78 • Number of events 48 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Weight decreased	8.6% 7/81 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	12.8% 10/78 • Number of events 10 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations Weight increased	6.2% 5/81 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	6.4% 5/78 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Investigations White blood cell count decreased	16.0% 13/81 • Number of events 34 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	19.2% 15/78 • Number of events 32 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Decreased appetite	17.3% 14/81 • Number of events 15 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	19.2% 15/78 • Number of events 16 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hyperglycaemia	6.2% 5/81 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	7.4% 6/81 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	11.5% 9/78 • Number of events 9 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hypokalaemia	13.6% 11/81 • Number of events 14 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	7.7% 6/78 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hypomagnesaemia	9.9% 8/81 • Number of events 12 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	12.8% 10/78 • Number of events 15 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Metabolism and nutrition disorders Hyponatraemia	13.6% 11/81 • Number of events 12 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	9.0% 7/78 • Number of events 10 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 5/81 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	11.5% 9/78 • Number of events 13 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Musculoskeletal and connective tissue disorders Back pain	6.2% 5/81 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	10.3% 8/78 • Number of events 13 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Dizziness	3.7% 3/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	7.7% 6/78 • Number of events 6 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Nervous system disorders Headache	6.2% 5/81 • Number of events 8 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	9.0% 7/78 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Psychiatric disorders Insomnia	8.6% 7/81 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	3.8% 3/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Renal and urinary disorders Proteinuria	11.1% 9/81 • Number of events 9 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	20.5% 16/78 • Number of events 21 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 9/81 • Number of events 12 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	3.8% 3/78 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.5% 2/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	14.1% 11/78 • Number of events 13 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Skin and subcutaneous tissue disorders Alopecia	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Skin and subcutaneous tissue disorders Pruritus	8.6% 7/81 • Number of events 11 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	9.0% 7/78 • Number of events 9 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Skin and subcutaneous tissue disorders Rash	11.1% 9/81 • Number of events 9 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	14.1% 11/78 • Number of events 15 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Skin and subcutaneous tissue disorders Urticaria	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	6.4% 5/78 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Vascular disorders Hypertension	18.5% 15/81 • Number of events 17 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	37.2% 29/78 • Number of events 36 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Endocrine disorders Hyperthyroidism	1.2% 1/81 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Gastrointestinal disorders Abdominal pain upper	6.2% 5/81 • Number of events 7 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
General disorders Mucosal inflammation	2.5% 2/81 • Number of events 3 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 9 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 5/81 • Number of events 5 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	1.3% 1/78 • Number of events 1 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Psychiatric disorders Anxiety	0.00% 0/81 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.
Skin and subcutaneous tissue disorders Dry skin	2.5% 2/81 • Number of events 2 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.	5.1% 4/78 • Number of events 4 • From the first study drug until the data cut-off on 25 August 2023 (up to approximately 30 months) All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any study drug.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

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