Trial Outcomes & Findings for Study of Pegilodecakin (LY3500518) With Nivolumab Compared to Nivolumab Alone Second-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer (NCT NCT03382912)

Last Updated: 2020-09-11

Results Overview

Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized)

Results posted on

2020-09-11

Participant Flow

Completer's included participants who had progression free survival events (Progressive Disease (PD) or death).

Participant milestones

Participant milestones
Measure	Pegilodecakin+Nivolumab Participants received Pegilodecakin subcutaneously at 0.8 milligrams (mg) (≤80 kilograms (kg) body weight) or 1.6 mg (\>80 kg body weight) once daily (QD) in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every 2 weeks (Q2W), or 480 mg every 4 weeks (Q4W).	Nivolumab Participants received Nivolumab on day 1 of each 14- or 28- day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every two weeks (Q2W), or 480 mg every 4 weeks (Q4W).
Overall Study STARTED	27	25
Overall Study Received at Least 1 Dose of Study Drug	27	24
Overall Study COMPLETED	21	13
Overall Study NOT COMPLETED	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Pegilodecakin+Nivolumab Participants received Pegilodecakin subcutaneously at 0.8 milligrams (mg) (≤80 kilograms (kg) body weight) or 1.6 mg (\>80 kg body weight) once daily (QD) in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every 2 weeks (Q2W), or 480 mg every 4 weeks (Q4W).	Nivolumab Participants received Nivolumab on day 1 of each 14- or 28- day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every two weeks (Q2W), or 480 mg every 4 weeks (Q4W).
Overall Study Physician Decision	0	1
Overall Study Sponsor Decision	6	6
Overall Study Withdrawal by Subject	0	5

Baseline Characteristics

Study of Pegilodecakin (LY3500518) With Nivolumab Compared to Nivolumab Alone Second-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pegilodecakin + Nivolumab n=27 Participants Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W, or 480 mg Q4W.	Nivolumab n=25 Participants Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W, or 480 mg Q4W.	Total n=52 Participants Total of all reporting groups
Sex: Female, Male Female	10 Participants n=99 Participants	11 Participants n=107 Participants	21 Participants n=206 Participants
Sex: Female, Male Male	17 Participants n=99 Participants	14 Participants n=107 Participants	31 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Age, Continuous	68.4 years STANDARD_DEVIATION 8.2 • n=99 Participants	65.9 years STANDARD_DEVIATION 10.4 • n=107 Participants	67.2 years STANDARD_DEVIATION 9.3 • n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=99 Participants	20 Participants n=107 Participants	44 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) White	23 Participants n=99 Participants	20 Participants n=107 Participants	43 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Region of Enrollment United States	27 Participants n=99 Participants	25 Participants n=107 Participants	52 Participants n=206 Participants

PRIMARY outcome

Timeframe: From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized)

Population: All randomized participants.

Outcome measures

Outcome measures
Measure	Pegilodecakin + Nivolumab n=27 Participants Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.	Nivolumab n=25 Participants Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]	14.8 Percentage of participants Interval 4.2 to 33.7	12.0 Percentage of participants Interval 2.6 to 31.2

SECONDARY outcome

Timeframe: From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)

Population: All randomized participants. Participants censored: Pegilodecakin + Nivolumab = 6 and Nivolumab = 5.

OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Pegilodecakin + Nivolumab n=27 Participants Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.	Nivolumab n=25 Participants Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.
Overall Survival (OS)	1.87 Months Interval 1.51 to 3.58	1.94 Months Interval 1.71 to 2.17

SECONDARY outcome

Timeframe: From Date of Randomization to Progressive Disease or Death Due to Any Cause (Up to 6 months after the last participant randomized)

Population: All randomized participants. Participants censored: Pegilodecakin + Nivolumab = 12 and Nivolumab = 16.

PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.

Outcome measures

Outcome measures
Measure	Pegilodecakin + Nivolumab n=27 Participants Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.	Nivolumab n=25 Participants Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.
Progression Free Survival (PFS)	6.70 Months Interval 3.09 to The upper 95% confidence interval was not achieved due to high censoring rate.	10.74 Months Interval 4.21 to The upper 95% confidence interval was not achieved due to high censoring rate.

SECONDARY outcome

Timeframe: From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months after the last participant randomization)

Population: All randomized participants.

Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Pegilodecakin + Nivolumab n=27 Participants Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.	Nivolumab n=25 Participants Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)	37.0 Percentage of participants Interval 19.4 to 57.6	28.0 Percentage of participants Interval 12.1 to 49.4

SECONDARY outcome

Timeframe: From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)

Population: All randomized participants who received at least one dose of study drug and had CR or PR responses. Participants censored: Pegilodecakin + Nivolumab = 3 and Nivolumab = 1.

Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

Outcome measures

Outcome measures
Measure	Pegilodecakin + Nivolumab n=4 Participants Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.	Nivolumab n=3 Participants Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.
Duration of Response	NA Months Interval 7.36 to Median and the upper 95% confidence interval was not achieved due to high censoring rate.	3.06 Months Interval 1.87 to The upper 95% confidence interval was not achieved due to high censoring rate.

Adverse Events

Pegilodecakin + Nivolumab

Serious events: 13 serious events

Other events: 27 other events

Deaths: 15 deaths

Nivolumab

Serious events: 9 serious events

Other events: 22 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Pegilodecakin + Nivolumab n=27 participants at risk Participants received Pegilodecakin subcutaneously at 0.8 mg (≤80 kg body weight) or 1.6 mg (\>80 kg body weight) once daily in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.	Nivolumab n=24 participants at risk Participants received Nivolumab on day 1 of each 14 or 28 day cycle over approximately 30 minutes IV infusion at 240 mg Q2W or 480 mg Q4W.
Cardiac disorders Cardiac arrest	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Cardiomyopathy	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Tachycardia	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 2 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Bezoar	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Asthenia	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Pyrexia	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pleural infection	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pneumonia	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	12.5% 3/24 • Number of events 3 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Rhinovirus infection	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Sepsis	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Streptococcal bacteraemia	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	7.4% 2/27 • Number of events 2 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Spinal fracture	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Dehydration	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyperkalaemia	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Anaemia	14.8% 4/27 • Number of events 4 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Haemolysis	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Thrombocytopenia	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Metabolic encephalopathy	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Syncope	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Mental status changes	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Acute kidney injury	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	7.4% 2/27 • Number of events 2 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	8.3% 2/24 • Number of events 4 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	8.3% 2/24 • Number of events 2 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 2 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Hypotension	0.00% 0/27 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Superior vena cava syndrome	3.7% 1/27 • Number of events 1 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/24 • Up to 23 Months All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.