Trial Outcomes & Findings for Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy (NCT NCT04471428)

NCT ID: NCT04471428

Last Updated: 2025-12-22

Results Overview

OS was defined as the time from randomization to death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 366 participants
• Primary outcome timeframe: Up to approximately 24 months
• Results posted on: 2025-12-22

Participant Flow

A total of 366 participants with metastatic non-small cell lung cancer (NSCLC) previously treated with anti-programmed death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibody and platinum-containing chemotherapy took part in the study at 97 investigative sites across 15 countries from 01 October 2020 to 17 January 2025.

Participants were randomized in a 1:1 ratio to receive either docetaxel monotherapy or atezolizumab & cabozantinib combination therapy. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis.

Participant milestones

Measure	Docetaxel Monotherapy Participants received docetaxel, 75 milligrams per square meter (mg/m\^2), intravenously (IV) on Day 1 of each 21-day cycle until unacceptable toxicity or disease progression (PD) or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib Participants received atezolizumab, 1200 milligrams (mg), IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given once a day (QD) on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Overall Study STARTED	180	186
Overall Study Safety-evaluable Population	167	185
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	180	186

Reasons for withdrawal

Measure	Docetaxel Monotherapy Participants received docetaxel, 75 milligrams per square meter (mg/m\^2), intravenously (IV) on Day 1 of each 21-day cycle until unacceptable toxicity or disease progression (PD) or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib Participants received atezolizumab, 1200 milligrams (mg), IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given once a day (QD) on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Overall Study Withdrawal by Subject	29	4
Overall Study Physician Decision	0	1
Overall Study Reason Not Specified	0	2
Overall Study Death	131	147
Overall Study Lost to Follow-up	0	3
Overall Study Study Terminated by Sponsor	20	29

Baseline Characteristics

Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy

Baseline characteristics by cohort

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Total n=366 Participants Total of all reporting groups	Docetaxel Monotherapy n=180 Participants Participants received docetaxel, 75 mg/m\^2, IV on Day 1 of each 21-day cycle until unacceptable toxicity or PD or loss of clinical benefit as determined by the investigator.
Age, Continuous	63.8 years STANDARD_DEVIATION 9.5 • n=102 Participants	64.1 years STANDARD_DEVIATION 9.4 • n=30 Participants	64.4 years STANDARD_DEVIATION 9.4 • n=18 Participants
Sex: Female, Male Female	52 Participants n=102 Participants	105 Participants n=30 Participants	53 Participants n=18 Participants
Sex: Female, Male Male	134 Participants n=102 Participants	261 Participants n=30 Participants	127 Participants n=18 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Asian	41 Participants n=102 Participants	94 Participants n=30 Participants	53 Participants n=18 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Black or African American	2 Participants n=102 Participants	3 Participants n=30 Participants	1 Participants n=18 Participants
Race (NIH/OMB) White	130 Participants n=102 Participants	241 Participants n=30 Participants	111 Participants n=18 Participants
Race (NIH/OMB) More than one race	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=102 Participants	28 Participants n=30 Participants	15 Participants n=18 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 Participants n=102 Participants	11 Participants n=30 Participants	7 Participants n=18 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	164 Participants n=102 Participants	322 Participants n=30 Participants	158 Participants n=18 Participants
Race/Ethnicity, Customized Not Stated	15 Participants n=102 Participants	27 Participants n=30 Participants	12 Participants n=18 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=102 Participants	6 Participants n=30 Participants	3 Participants n=18 Participants

PRIMARY outcome

Timeframe: Up to approximately 24 months

Population: The ITT population included all randomized participants, whether or not the participant received the assigned treatment.

OS was defined as the time from randomization to death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Overall Survival (OS)	10.7 months Interval 8.8 to 12.3	10.5 months Interval 8.6 to 13.0

SECONDARY outcome

Timeframe: Up to approximately 24 months

Population: The ITT population included all randomized participants, whether or not the participant received the assigned treatment.

PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1), or death from any cause (whichever occurred first). PD was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. In addition, the sum of diameters also demonstrated an absolute increase of ≥ 5 millimeters (mm). Participants who were alive and did not experience PD at the time of analysis, were censored on the date of last tumor assessment. Participants with no post-baseline tumor assessment were censored at the date of randomization. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Progression-Free Survival (PFS) as Determined by Investigator	4.6 months Interval 4.1 to 5.6	4.0 months Interval 3.1 to 4.4

SECONDARY outcome

Timeframe: Up to approximately 24 months

Population: The ITT population included all randomized participants, whether or not the participant received the assigned treatment.

Confirmed ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions. In addition, any pathological lymph nodes must have a reduction in short axis to < 10 mm. PR= at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. 95% CIs for rates were constructed using the Clopper-Pearson method. Percentages have been rounded off.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Confirmed Objective Response Rate (ORR) as Determined by Investigator	11.8 percentage of participants Interval 7.56 to 17.36	13.3 percentage of participants Interval 8.73 to 19.19

SECONDARY outcome

Timeframe: Up to approximately 24 months

Population: Participants in the ITT population who had a confirmed objective response (CR or PR) as determined by the investigator per RECIST v1.1 were included in the analysis.

DOR for participants with confirmed ORR=time from first documented objective response to PD, as determined by investigator per RECIST v1.1, or death from any cause (whichever occurred first). PD=≥ 20% increase in sum of longest diameters of target lesions, taking as reference smallest sum of longest diameters of target lesions recorded since treatment started, including screening, or appearance of new lesions. In addition, sum of diameters also demonstrated an absolute increase of ≥ 5 mm. Confirmed ORR=percentage of participants with a CR or PR on two consecutive occasions ≥4 weeks apart, as determined by investigator per RECIST v1.1. CR= disappearance of all target lesions. PR=≥ 30% decrease in sum of diameters of all target lesions. Participants who had not progressed and who did not die at the time of analysis were censored at the time of last tumor assessment date. Kaplan-Meier method was used to estimate median. 95% CI for median was computed using Brookmeyer and Crowley method.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=22 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=24 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Duration of Response (DOR) as Determined by Investigator	5.55 months Interval 3.12 to 10.25	4.30 months Interval 3.29 to 5.62

SECONDARY outcome

Timeframe: Up to approximately 24 months

Population: The ITT population included all randomized participants, whether or not the participant received the assigned treatment. Participants without a confirmed deterioration at the time of analysis were censored at the last time they were known to have not deteriorated.

TTCD analyses was performed for patient-reported PF (items 1 to 5) of European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). The PF was measured on 4-point scale (1='Not at all' to 4='Very much'). TTCD for PF was defined as time from date of randomization to first confirmed clinically meaningful decrease from baseline in PF score held for at least 2 consecutive assessments or initial clinically meaningful decrease from baseline followed by death from any cause within 21 days or until next tumor assessment, whichever occurs first. A score change of ≥ of 10-point on EORTC QLQ-C30 PF scale was determined as being clinically meaningful. Scores were averaged, transformed to 0-100 scale; where higher score represented high/healthy level of functioning. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Time to Confirmed Deterioration (TTCD) in Patient-reported Physical Functioning (PF)	7.7 months Interval 4.8 to 14.7	5.6 months Interval 4.0 to Upper limit of 95% confidence interval (CI) was not estimable as there were not enough events after the median estimate to satisfy constraints required to calculate the upper limit of interval.

SECONDARY outcome

Timeframe: Up to approximately 24 months

Population: Participants without a confirmed deterioration at the time of analysis were censored at the last time they were known to have not deteriorated. The ITT population included all randomized participants, whether or not the participant received the assigned treatment. Only responders were analysed in this endpoint.

TTCD analyses was performed for GHS and quality of life (QoL) (items 29 and 30) of EORTC QLQ-C30. GHS/ QoL items were scored on a 7-point scale that ranges from "very poor" to "excellent." TTCD for GHS/QoL was defined as the time from the date of randomization to the first confirmed clinically meaningful decrease from baseline in GHS/QoL score held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 21 days or until the next tumor assessment, whichever occurs first. A score change of ≥ 10-point on the EORTC QLQ-C30 GHS/QoL scale was determined as being clinically meaningful. Scores were averaged, transformed to 0-100 scale; where higher score for GHS/QoL= better health-related QoL. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
TTCD in Patient-reported Global Health Status (GHS)	8.1 months Interval 5.6 to 14.5	14.1 months Interval 6.3 to Upper limit of 95% confidence interval (CI) was not estimable as there were not enough events after the median estimate to satisfy constraints required to calculate the upper limit of interval.

SECONDARY outcome

Timeframe: 6 months and 1 year

Population: The ITT population included all randomized participants, whether or not the participant received the assigned treatment.

PFS rates were defined as the percentage of participants alive and without PD as assessed by the investigator according to RECIST v1.1 at 6 months and 1 year after randomization. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints, including baseline. In addition, the sum of diameters also demonstrated an absolute increase of ≥ 5 mm. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. Percentages have been rounded off.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
PFS Rates Assessed by Investigator At 6 months	39.51 percentage of participants Interval 32.42 to 46.59	23.66 percentage of participants Interval 16.98 to 30.33
PFS Rates Assessed by Investigator At 1 year	14.70 percentage of participants Interval 9.43 to 19.97	8.38 percentage of participants Interval 3.95 to 12.8

SECONDARY outcome

Timeframe: 1 and 2 years

Population: The ITT population is defined as all randomized participants, whether or not the participant received the assigned treatment. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. At the time of the analysis, there were no participants with 24 months or more of survival follow-up, therefore, survival rate at the 2-year timepoint was not estimable.

OS rates were defined as the percentage of participants who were alive at 1 and 2 years. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. Percentages have been rounded off.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=186 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=180 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
OS Rates 1 year	43.27 percentage of participants Interval 35.97 to 50.57	44.12 percentage of participants Interval 36.2 to 52.05
OS Rates 2 years	NA percentage of participants Participants alive at the time of the analysis of the 2-year time point were censored at the date when they were last known to be alive as documented by the investigator. There were no participants with 24 months or more of survival follow-up, therefore, survival rate at the 2-year time point was not estimable.	NA percentage of participants Participants alive at the time of the analysis of the 2-year time point were censored at the date when they were last known to be alive as documented by the investigator. There were no participants with 24 months or more of survival follow-up, therefore, survival rate at the 2-year time point was not estimable.

SECONDARY outcome

Timeframe: Up to approximately 41.4 months

Population: Safety-evaluable population included all randomized participants who had received any amount of study drug, with participants grouped according to the actual treatment received.

An AE was defined as any untoward medical occurrence in a clinical investigation patient administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition not present at baseline; any deterioration in a laboratory value or other clinical test; AEs related to a protocol-mandated intervention. AEs were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v5.0). Percentages have been rounded off.

Outcome measures

Measure	Atezolizumab + Cabozantinib n=185 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=167 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Percentage of Participants With Adverse Events (AEs)	98.4 percentage of participants	94.0 percentage of participants

SECONDARY outcome

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

Population: Pharmacokinetic (PK)-evaluable population for atezolizumab included all participants who had received any dose of atezolizumab and who had evaluable PK samples. Number analyzed is the number of participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Measure	Atezolizumab + Cabozantinib Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=185 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 2 Day 1	—	96.8 microgram/milliliter (μg/ml) Geometric Coefficient of Variation 48.1
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 1 Day 1	—	NA microgram/milliliter (μg/ml) Geometric Coefficient of Variation NA The data was not evaluable as all samples were below limit of quantitation (BLQ)
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 3 Day 1	—	124 microgram/milliliter (μg/ml) Geometric Coefficient of Variation 104.4
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 4 Day 1	—	167 microgram/milliliter (μg/ml) Geometric Coefficient of Variation 47.7
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 8 Day 1	—	194 microgram/milliliter (μg/ml) Geometric Coefficient of Variation 62.4
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 12 Day 1	—	233 microgram/milliliter (μg/ml) Geometric Coefficient of Variation 44.7
Minimum Serum Concentration (Cmin) of Atezolizumab Cycle 16 Day 1	—	209 microgram/milliliter (μg/ml) Geometric Coefficient of Variation 56.1

SECONDARY outcome

Timeframe: 30 minutes (min) postdose on Day 1 of Cycle 1 (Cycle= 21 days)

Population: PK-evaluable population included all participants who had received any dose of atezolizumab and who had evaluable PK samples.

Outcome measures

Measure	Atezolizumab + Cabozantinib Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=185 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Maximum Serum Concentration (Cmax) of Atezolizumab	—	450 μg/mL Geometric Coefficient of Variation 34.0

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (Cycle= 21 days)

Population: PK-evaluable population included all participants who had received any dose of cabozantinib and who had evaluable PK samples. Number analyzed is the number of participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Measure	Atezolizumab + Cabozantinib Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=185 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Minimum Plasma Concentration (Cmin) of Cabozantinib Cycle 1 Day 1	—	NA μg/mL Geometric Coefficient of Variation NA The data was not evaluable as all samples were Below Limit of Quantitation (BLQ)
Minimum Plasma Concentration (Cmin) of Cabozantinib Cycle 2 Day 1	—	0.746 μg/mL Geometric Coefficient of Variation 111.7
Minimum Plasma Concentration (Cmin) of Cabozantinib Cycle 3 Day 1	—	0.418 μg/mL Geometric Coefficient of Variation 640.7
Minimum Plasma Concentration (Cmin) of Cabozantinib Cycle 4 Day 1	—	0.469 μg/mL Geometric Coefficient of Variation 234.4
Minimum Plasma Concentration (Cmin) of Cabozantinib Cycle 5 Day 1	—	0.303 μg/mL Geometric Coefficient of Variation 402.3

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (Cycle= 21 days)

Population: Cmax was not collected for this outcome measure because PK of cabozantinib was well characterized through the cabozantinib development for mono- therapy. An established population PK model for cabozantinib is available for the PK data from NCT04471428 (study GO41892). The PK data collected in the current study is sufficient for the population PK model to characterize the exposure of cabozantinib in this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and post-treatment follow-up (≤ 30 days after final dose) (Cycle= 21 days)

Population: Safety-evaluable population included all randomized participants who had received any amount of study drug, with participants grouped according to the actual treatment received. Overall number analyzed is the number of participants with data available for analysis.

Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). The total number of participants who developed ADAs to atezolizumab was determined by summing the ADA-positive participants across all timepoints.

Outcome measures

Measure	Atezolizumab + Cabozantinib Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=177 Participants Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab ADA Prevalence at Baseline	—	2 Participants
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab ADA Incidence after treatment	—	37 Participants

Adverse Events

Docetaxel Monotherapy

Serious events: 58 serious events

Other events: 148 other events

Deaths: 131 deaths

Atezolizumab + Cabozantinib

Serious events: 76 serious events

Other events: 173 other events

Deaths: 147 deaths

Serious adverse events

Measure	Docetaxel Monotherapy n=167 participants at risk Participants received docetaxel, 75 mg/m\^2, IV on Day 1 of each 21-day cycle until unacceptable toxicity or PD or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=185 participants at risk Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Blood and lymphatic system disorders Anaemia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Blood and lymphatic system disorders Febrile neutropenia	4.8% 8/167 • Number of events 9 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Blood and lymphatic system disorders Leukopenia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Blood and lymphatic system disorders Neutropenia	1.8% 3/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Acute myocardial infarction	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Atrial fibrillation	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.1% 2/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Atrial flutter	1.2% 2/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Cardiac tamponade	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.1% 2/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Myocardial infarction	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Myocardial ischaemia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Myocarditis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Pneumopericardium	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Cardiac disorders Supraventricular tachycardia	0.60% 1/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Anorectal disorder	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Colitis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Diarrhoea	1.8% 3/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	2.2% 4/185 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Duodenal ulcer	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Dysphagia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Gastritis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Intestinal fistula	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Intestinal perforation	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Large intestine perforation	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Oesophagitis	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Pancreatitis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Vomiting	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.6% 3/185 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Asthenia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.6% 3/185 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Chest pain	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Condition aggravated	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Death	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.6% 3/185 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Fatigue	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Generalised oedema	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Malaise	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Mucosal inflammation	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Pain	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Pyrexia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	2.7% 5/185 • Number of events 6 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Sudden cardiac death	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Sudden death	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Hepatobiliary disorders Hepatic failure	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Immune system disorders Haemophagocytic lymphohistiocytosis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Immune system disorders Infusion related hypersensitivity reaction	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Atypical pneumonia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Bacterial colitis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations COVID-19	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.1% 2/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations COVID-19 pneumonia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Encephalitis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Herpes zoster	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Large intestine infection	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Meningitis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Mycobacterium avium complex infection	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Oesophageal candidiasis	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Pneumonia	6.0% 10/167 • Number of events 10 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.4% 10/185 • Number of events 10 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Respiratory tract infection	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Sepsis	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.1% 2/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Urinary tract infection	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Vascular device infection	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	2.2% 4/185 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Viral infection	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Injury, poisoning and procedural complications Spinal fracture	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Lymphocyte count decreased	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Neutrophil count decreased	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations White blood cell count decreased	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Decreased appetite	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hyperglycaemia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Fistula	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Muscular weakness	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Ataxia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Encephalopathy	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Haemorrhage intracranial	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Status epilepticus	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Toxic encephalopathy	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Transient ischaemic attack	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Psychiatric disorders Confusional state	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Psychiatric disorders Depression	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Psychiatric disorders Suicide attempt	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Renal and urinary disorders Acute kidney injury	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Renal and urinary disorders Bladder disorder	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Bronchial fistula	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.8% 3/167 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.1% 2/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.0% 5/167 • Number of events 5 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.6% 3/185 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.6% 3/185 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.1% 2/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pulmonary infarction	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.2% 2/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.4% 4/167 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Hidradenitis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Rash	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	1.6% 3/185 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Vascular disorders Deep vein thrombosis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Vascular disorders Hypertensive crisis	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.00% 0/185 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Vascular disorders Intermittent claudication	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Endocrine disorders Adrenal insufficiency	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Anal abscess	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations Pneumonia necrotising	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Lipase increased	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Cachexia	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	0.54% 1/185 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.

Other adverse events

Measure	Docetaxel Monotherapy n=167 participants at risk Participants received docetaxel, 75 mg/m\^2, IV on Day 1 of each 21-day cycle until unacceptable toxicity or PD or loss of clinical benefit as determined by the investigator.	Atezolizumab + Cabozantinib n=185 participants at risk Participants received atezolizumab, 1200 mg, IV, on Day 1 of each 21-day cycle along with cabozantinib, 40 mg, orally, given QD on Days 1-21 of each cycle until unacceptable toxicity, PD, or loss of clinical benefit as determined by the investigator.
Blood and lymphatic system disorders Anaemia	22.8% 38/167 • Number of events 47 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	13.0% 24/185 • Number of events 26 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Blood and lymphatic system disorders Thrombocytopenia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	9.2% 17/185 • Number of events 20 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Endocrine disorders Hypothyroidism	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	16.2% 30/185 • Number of events 32 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Abdominal pain	3.0% 5/167 • Number of events 5 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	11.4% 21/185 • Number of events 27 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Abdominal pain upper	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.9% 11/185 • Number of events 12 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Constipation	10.2% 17/167 • Number of events 17 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	16.8% 31/185 • Number of events 35 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Diarrhoea	22.8% 38/167 • Number of events 62 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	44.9% 83/185 • Number of events 134 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Nausea	17.4% 29/167 • Number of events 42 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	25.4% 47/185 • Number of events 56 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Stomatitis	7.8% 13/167 • Number of events 14 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	15.1% 28/185 • Number of events 30 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Gastrointestinal disorders Vomiting	6.6% 11/167 • Number of events 14 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	15.7% 29/185 • Number of events 36 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Asthenia	24.0% 40/167 • Number of events 45 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	23.2% 43/185 • Number of events 53 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Fatigue	26.3% 44/167 • Number of events 48 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	22.7% 42/185 • Number of events 48 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Malaise	5.4% 9/167 • Number of events 9 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	2.7% 5/185 • Number of events 5 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Mucosal inflammation	5.4% 9/167 • Number of events 10 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.9% 11/185 • Number of events 17 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Oedema peripheral	7.2% 12/167 • Number of events 15 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	4.3% 8/185 • Number of events 8 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
General disorders Pyrexia	7.2% 12/167 • Number of events 12 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	10.8% 20/185 • Number of events 21 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Infections and infestations COVID-19	2.4% 4/167 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	7.6% 14/185 • Number of events 15 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Alanine aminotransferase increased	4.2% 7/167 • Number of events 7 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	19.5% 36/185 • Number of events 53 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Aspartate aminotransferase increased	2.4% 4/167 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	16.8% 31/185 • Number of events 42 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Neutrophil count decreased	7.2% 12/167 • Number of events 19 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	4.3% 8/185 • Number of events 17 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Platelet count decreased	0.00% 0/167 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	8.1% 15/185 • Number of events 27 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Weight decreased	3.6% 6/167 • Number of events 7 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	16.2% 30/185 • Number of events 30 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Decreased appetite	16.8% 28/167 • Number of events 31 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	31.9% 59/185 • Number of events 64 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hypoalbuminaemia	7.2% 12/167 • Number of events 16 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	10.8% 20/185 • Number of events 23 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hypocalcaemia	4.2% 7/167 • Number of events 7 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	10.8% 20/185 • Number of events 35 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hypokalaemia	4.8% 8/167 • Number of events 9 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	8.1% 15/185 • Number of events 15 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hypomagnesaemia	2.4% 4/167 • Number of events 5 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	12.4% 23/185 • Number of events 29 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hyponatraemia	6.0% 10/167 • Number of events 10 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	6.5% 12/185 • Number of events 17 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Arthralgia	12.0% 20/167 • Number of events 23 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	14.1% 26/185 • Number of events 31 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Back pain	4.2% 7/167 • Number of events 9 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	9.7% 18/185 • Number of events 20 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Muscle spasms	1.8% 3/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.9% 11/185 • Number of events 13 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Myalgia	11.4% 19/167 • Number of events 23 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.9% 11/185 • Number of events 14 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 4/167 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	6.5% 12/185 • Number of events 15 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Dizziness	3.0% 5/167 • Number of events 5 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	7.6% 14/185 • Number of events 15 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Dysgeusia	6.0% 10/167 • Number of events 14 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	10.8% 20/185 • Number of events 24 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Headache	8.4% 14/167 • Number of events 18 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	7.6% 14/185 • Number of events 16 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Nervous system disorders Neuropathy peripheral	5.4% 9/167 • Number of events 9 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	2.2% 4/185 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Psychiatric disorders Insomnia	4.2% 7/167 • Number of events 7 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	9.2% 17/185 • Number of events 18 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Renal and urinary disorders Proteinuria	1.8% 3/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	11.9% 22/185 • Number of events 30 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Cough	7.2% 12/167 • Number of events 14 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	10.8% 20/185 • Number of events 25 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.60% 1/167 • Number of events 1 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	8.6% 16/185 • Number of events 19 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.0% 25/167 • Number of events 25 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	14.6% 27/185 • Number of events 29 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Alopecia	24.0% 40/167 • Number of events 40 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	2.2% 4/185 • Number of events 4 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Dry skin	4.2% 7/167 • Number of events 7 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.9% 11/185 • Number of events 11 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	21.6% 40/185 • Number of events 54 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Pruritus	3.6% 6/167 • Number of events 7 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	8.1% 15/185 • Number of events 19 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Skin and subcutaneous tissue disorders Rash	7.8% 13/167 • Number of events 14 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	9.2% 17/185 • Number of events 20 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Vascular disorders Hypertension	1.2% 2/167 • Number of events 3 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	9.2% 17/185 • Number of events 25 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Investigations Amylase increased	1.2% 2/167 • Number of events 2 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	5.4% 10/185 • Number of events 11 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.
Metabolism and nutrition disorders Hypophosphataemia	3.0% 5/167 • Number of events 5 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.	6.5% 12/185 • Number of events 13 • All-cause mortality: Up to 44.6 months SAE and other AEs: Up to 41.4 months Safety-evaluable population which included all randomized participants who had received any amount of study drug. A total of 14 participants did not receive any study treatment and were therefore excluded from the safety analysis. All-cause mortality reported for deaths that occurred during study based on ITT population.

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