Trial Outcomes & Findings for Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200) (NCT NCT02395172)

NCT ID: NCT02395172

Last Updated: 2020-08-03

Results Overview

The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 792 participants
• Primary outcome timeframe: Time from date of randomization up to 1420 days
• Results posted on: 2020-08-03

Participant Flow

First participant signed informed consent: 24 Mar 2015, Clinical data cut-off: 04 March 2019.

Participant milestones

Measure	Avelumab Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Overall Study STARTED	396	396
Overall Study Treated	393	365
Overall Study COMPLETED	393	365
Overall Study NOT COMPLETED	3	31

Reasons for withdrawal

Measure	Avelumab Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Overall Study Participants randomized but not treated	3	31

Baseline Characteristics

Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)

Baseline characteristics by cohort

Measure	Avelumab n=396 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=396 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Total n=792 Participants Total of all reporting groups
Age, Continuous	62.8 years STANDARD_DEVIATION 9.99 • n=5 Participants	62.5 years STANDARD_DEVIATION 9.65 • n=7 Participants	62.7 years STANDARD_DEVIATION 9.81 • n=5 Participants
Sex: Female, Male Female	127 Participants n=5 Participants	123 Participants n=7 Participants	250 Participants n=5 Participants
Sex: Female, Male Male	269 Participants n=5 Participants	273 Participants n=7 Participants	542 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	59 Participants n=5 Participants	42 Participants n=7 Participants	101 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	297 Participants n=5 Participants	307 Participants n=7 Participants	604 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	40 Participants n=5 Participants	47 Participants n=7 Participants	87 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	102 Participants n=5 Participants	114 Participants n=7 Participants	216 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized White	273 Participants n=5 Participants	262 Participants n=7 Participants	535 Participants n=5 Participants
Race/Ethnicity, Customized Not collected at the site	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time from date of randomization up to 1420 days

Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with greater than or equal to (\>=) 1 percentage (%) of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.

The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.

Outcome measures

Measure	Avelumab n=264 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=265 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS)	11.4 months Interval 9.4 to 13.8	10.6 months Interval 8.5 to 12.9

SECONDARY outcome

Timeframe: Time from date of randomization up to 1420 days

Population: Full analysis set (FAS) included all participants who were randomized to study.

The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.

Outcome measures

Measure	Avelumab n=396 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=396 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Overall Survival (OS) Time in Full Analysis Set Population	10.6 months Interval 9.2 to 12.3	9.9 months Interval 8.1 to 11.9

SECONDARY outcome

Timeframe: Time from date of randomization up to 907 days

Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with \>= 1 percentage of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.

PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.

Outcome measures

Measure	Avelumab n=264 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=265 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population	3.4 months Interval 2.7 to 4.9	4.1 months Interval 3.0 to 5.3

SECONDARY outcome

Timeframe: Time from date of randomization up to 907 days

Population: Full analysis set (FAS) included all participants who were randomized to study.

PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.

Outcome measures

Measure	Avelumab n=396 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=396 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Progression-Free Survival (PFS) Time in Full Analysis Set Population	2.8 months Interval 2.7 to 3.5	4.2 months Interval 3.3 to 5.2

SECONDARY outcome

Timeframe: Time from date of randomization up to 907 days

Population: Full analysis set (FAS) included all participants who were randomized to study.

Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.

Outcome measures

Measure	Avelumab n=396 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=396 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population Complete Response	5 Participants	2 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population Partial Response	54 Participants	42 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population Stable Disease	129 Participants	158 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population Non-complete Response/ Non-progressive Disease	5 Participants	13 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population Progressive Disease	150 Participants	82 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population Not Evaluable	53 Participants	99 Participants

SECONDARY outcome

Timeframe: Time from date of randomization up to 907 days

Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with \>= 1 percentage of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.

Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.

Outcome measures

Measure	Avelumab n=264 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=265 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population Stable Disease	86 Participants	104 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population Non-complete Response/ Non-progressive Disease	4 Participants	12 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population Complete Response	4 Participants	1 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population Partial Response	46 Participants	30 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population Progressive Disease	93 Participants	57 Participants
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population Not Evaluable	31 Participants	61 Participants

SECONDARY outcome

Timeframe: Time from date of randomization up to 907 days

Population: Full analysis set (FAS) included all participants who were randomized to study.

Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.

Outcome measures

Measure	Avelumab n=396 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=396 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population	14.9 percentage of participants Interval 11.5 to 18.8	11.1 percentage of participants Interval 8.2 to 14.6

SECONDARY outcome

Timeframe: Time from date of randomization up to 907 days

Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with \>= 1 percentage of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.

Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.

Outcome measures

Measure	Avelumab n=264 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=265 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population	18.9 percentage of participants Interval 14.4 to 24.2	11.7 percentage of participants Interval 8.1 to 16.2

SECONDARY outcome

Timeframe: Baseline, End of treatment visit (up to Week 124)

Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signified the participants analyzed in this outcome.

The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions).

Outcome measures

Measure	Avelumab n=172 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=196 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)	-0.1245 units on a scale Standard Deviation 0.28021	-0.0988 units on a scale Standard Deviation 0.26615

SECONDARY outcome

Timeframe: Baseline, End of treatment visit (up to Week 124)

Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signified the participants analyzed in this outcome.

EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.

Outcome measures

Measure	Avelumab n=171 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=196 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)	-8.1 millimeter Standard Deviation 22.06	-7.0 millimeter Standard Deviation 21.12

SECONDARY outcome

Timeframe: Baseline, End of treatment visit (up to Week 124)

Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signified the participants analyzed in this outcome.

EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.

Outcome measures

Measure	Avelumab n=172 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=196 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT)	-9.79 units on a scale Standard Deviation 24.506	-9.44 units on a scale Standard Deviation 18.933

SECONDARY outcome

Timeframe: Baseline, End of treatment visit (up to Week 124)

Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.

EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).

Outcome measures

Measure	Avelumab n=348 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=333 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Dyspnea	9.95 units on a scale Standard Deviation 22.094	8.52 units on a scale Standard Deviation 21.285
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Coughing	-0.58 units on a scale Standard Deviation 30.263	-2.03 units on a scale Standard Deviation 32.582
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Sore Mouth	0.78 units on a scale Standard Deviation 17.643	3.72 units on a scale Standard Deviation 24.920
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Dysphagia	5.62 units on a scale Standard Deviation 18.401	4.23 units on a scale Standard Deviation 21.538
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Pain in Chest	4.84 units on a scale Standard Deviation 28.993	0.34 units on a scale Standard Deviation 26.935
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Pain in Other Parts	8.77 units on a scale Standard Deviation 34.410	6.60 units on a scale Standard Deviation 30.978
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Pain in Arm or Shoulder	5.62 units on a scale Standard Deviation 28.852	0.85 units on a scale Standard Deviation 29.439
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Hemoptysis	0.19 units on a scale Standard Deviation 14.191	-0.34 units on a scale Standard Deviation 16.832
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Peripheral Neuropathy	0.19 units on a scale Standard Deviation 20.550	9.81 units on a scale Standard Deviation 30.015
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) Alopecia	-3.10 units on a scale Standard Deviation 20.789	30.80 units on a scale Standard Deviation 42.582

SECONDARY outcome

Timeframe: Time from date of randomization up to 1420 days

Population: Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

Outcome measures

Measure	Avelumab n=393 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=365 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death Drug Related TEAEs	252 Participants	313 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death TEAEs	375 Participants	346 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death TESAEs	167 Participants	145 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death TEAEs Leading to Death	64 Participants	51 Participants

SECONDARY outcome

Timeframe: Time from date of randomization up to 1420 days

Population: Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event.

Outcome measures

Measure	Avelumab n=393 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=365 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity Grade 3 or Higher	209 Participants	247 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity Grade 4 or Higher	87 Participants	122 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity Grade 5	63 Participants	51 Participants

SECONDARY outcome

Timeframe: Time from date of randomization up to 1420 days

Population: Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination.

Outcome measures

Measure	Avelumab n=393 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=365 Participants Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline score 5	1 Participants	0 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline Missing	0 Participants	6 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline score 0	6 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline score 1	157 Participants	172 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline score 3	23 Participants	8 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline score 4	3 Participants	2 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline Missing	12 Participants	23 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline score 0	52 Participants	55 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline score 1	67 Participants	41 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline score 2	19 Participants	12 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline score 3	5 Participants	2 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 0, worst post-baseline score 4	0 Participants	1 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline score 2	47 Participants	41 Participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score Baseline score 1, worst post-baseline score 5	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Time from date of randomization up to 1420 days

Population: Full analysis set (FAS) included all participants who were randomized to study. Here, "Overall Number of Participants Analyzed" signified participants with at least on valid ADA result at any time point.

Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported.

Outcome measures

Measure	Avelumab n=388 Participants Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab ADAs to Avelumab	58 Participants	—
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab NAbs to Avelumab	14 Participants	—

Adverse Events

Avelumab

Serious events: 167 serious events

Other events: 320 other events

Deaths: 316 deaths

Docetaxel

Serious events: 145 serious events

Other events: 307 other events

Deaths: 297 deaths

Serious adverse events

Measure	Avelumab n=393 participants at risk Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=365 participants at risk Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
General disorders Disease progression	10.4% 41/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	7.1% 26/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Asthenia	1.5% 6/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Death	1.5% 6/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.1% 4/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Pain	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Chest pain	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Chills	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders General physical health deterioration	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Non-cardiac chest pain	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Oedema peripheral	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Fatigue	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Malaise	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Mucosal inflammation	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Pyrexia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Sudden cardiac death	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.8% 11/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.9% 7/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 10/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.5% 6/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.3% 5/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 4/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.1% 4/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Oesophagobronchial fistula	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Pneumonia	2.3% 9/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	5.2% 19/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Respiratory tract infection	1.0% 4/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.4% 5/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Lung infection	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Sepsis	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Appendicitis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Encephalitis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Gastroenteritis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Pleural infection	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Pneumonia streptococcal	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Postoperative wound infection	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Bronchitis	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.1% 4/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Diabetic gangrene	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Klebsiella infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Lower respiratory tract infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.1% 4/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Meningitis	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Neutropenic infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Neutropenic sepsis	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Peritonitis	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Pneumocystis jirovecii pneumonia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Septic shock	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.4% 5/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Serratia infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Soft tissue infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Streptococcal infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Upper respiratory tract infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Urinary tract infection	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Urosepsis	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Infusion related reaction	2.5% 10/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Femoral neck fracture	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Brain contusion	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Femur fracture	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.3% 5/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Atrial fibrillation	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Pericardial effusion	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiac arrest	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Acute coronary syndrome	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Angina unstable	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Autoimmune myocarditis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiac failure	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiac failure acute	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiac tamponade	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiomyopathy	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Myocardial infarction	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Acute myocardial infarction	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiac failure congestive	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Cardiovascular insufficiency	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Abdominal pain	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Colitis	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Ascites	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Diarrhoea	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.4% 5/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Gastric haemorrhage	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Gastritis erosive	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Gastrointestinal pain	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Ileus	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Melaena	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Subileus	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Constipation	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Dysphagia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Ileus paralytic	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Intestinal perforation	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Nausea	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Vomiting	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Hypercalcaemia	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Hyperglycaemia	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Hyperkalaemia	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Decreased appetite	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Hyponatraemia	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Dehydration	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Hypophagia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Depressed level of consciousness	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Balance disorder	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Cerebrovascular accident	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Hemiparesis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Hemiplegia	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Neurotoxicity	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Post herpetic neuralgia	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Seizure	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Syncope	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Cerebral infarction	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Haemorrhage intracranial	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Loss of consciousness	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Paraesthesia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Spinal cord compression	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Back pain	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Arthralgia	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Pain in extremity	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Renal and urinary disorders Acute kidney injury	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Renal and urinary disorders Nephrolithiasis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Renal and urinary disorders Renal impairment	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Vascular disorders Superior vena cava syndrome	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Vascular disorders Aortic aneurysm	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Vascular disorders Intermittent claudication	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Vascular disorders Peripheral arterial occlusive disease	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Vascular disorders Deep vein thrombosis	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Vascular disorders Hypotension	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.55% 2/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Anaemia	1.0% 4/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	6.0% 22/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Leukopenia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Neutropenia	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	2.7% 10/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Endocrine disorders Adrenal insufficiency	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Endocrine disorders Autoimmune thyroiditis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Hepatobiliary disorders Cholangitis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Hepatobiliary disorders Hepatic function abnormal	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Immune system disorders Hypersensitivity	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Skin and subcutaneous tissue disorders Angioedema	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Ear and labyrinth disorders Vertigo	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Eye disorders Vision blurred	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Gamma-glutamyltransferase increased	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Neutrophil count decreased	0.00% 0/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	1.1% 4/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Psychiatric disorders Confusional state	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Cystic lung disease	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Cardiac disorders Left ventricular dysfunction	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Colitis ulcerative	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Thrombotic cerebral infarction	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Renal and urinary disorders Renal failure	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Hepatobiliary disorders Cholelithiasis	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Alanine aminotransferase increased	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Aspartate aminotransferase increased	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Blood creatine phosphokinase increased	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Psychiatric disorders Agitation	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.00% 0/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

Other adverse events

Measure	Avelumab n=393 participants at risk Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Docetaxel n=365 participants at risk Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
General disorders Fatigue	17.8% 70/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	18.1% 66/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Asthenia	14.0% 55/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	17.5% 64/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Pyrexia	12.7% 50/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	9.0% 33/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Chills	7.4% 29/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.82% 3/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Oedema peripheral	5.3% 21/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	10.1% 37/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Malaise	2.3% 9/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	7.1% 26/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
General disorders Mucosal inflammation	1.3% 5/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	6.0% 22/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Cough	19.6% 77/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	12.6% 46/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Dyspnoea	19.1% 75/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	14.8% 54/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Productive cough	6.4% 25/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	2.2% 8/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.4% 25/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	4.1% 15/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Nausea	14.2% 56/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	15.6% 57/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Constipation	11.5% 45/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	11.8% 43/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Diarrhoea	11.2% 44/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	18.4% 67/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Vomiting	9.7% 38/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	7.7% 28/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Gastrointestinal disorders Stomatitis	2.3% 9/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	11.5% 42/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Back pain	12.0% 47/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	4.7% 17/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Arthralgia	6.9% 27/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	8.2% 30/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.4% 25/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	4.1% 15/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 23/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	3.3% 12/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Musculoskeletal and connective tissue disorders Myalgia	4.3% 17/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	11.8% 43/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Metabolism and nutrition disorders Decreased appetite	20.1% 79/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	20.8% 76/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Injury, poisoning and procedural complications Infusion related reaction	14.2% 56/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	2.2% 8/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Skin and subcutaneous tissue disorders Rash	8.4% 33/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	4.7% 17/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Skin and subcutaneous tissue disorders Pruritus	6.6% 26/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	3.6% 13/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Weight decreased	12.7% 50/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	8.2% 30/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations Neutrophil count decreased	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	9.3% 34/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Investigations White blood cell count decreased	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	5.8% 21/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Anaemia	12.7% 50/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	22.2% 81/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Blood and lymphatic system disorders Neutropenia	0.51% 2/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	13.2% 48/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Headache	7.6% 30/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	5.2% 19/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Neuropathy peripheral	1.5% 6/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	9.0% 33/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Peripheral sensory neuropathy	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	7.4% 27/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Nervous system disorders Dysgeusia	0.25% 1/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	6.3% 23/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Infections and infestations Upper respiratory tract infection	7.1% 28/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	3.3% 12/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Endocrine disorders Hypothyroidism	6.1% 24/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	0.27% 1/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Psychiatric disorders Insomnia	4.8% 19/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	6.0% 22/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Skin and subcutaneous tissue disorders Alopecia	0.76% 3/393 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.	26.6% 97/365 • Time from date of randomization up to 1420 days. Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place