An Open-Label, Multicenter Clinical Trial With Nivolumab (BMS-936558) Monotherapy in Subjects With Advanced or Metastatic Squamous Cell (Sq) Non-Small Cell Lung Cancer (NSCLC) Who Have Received at Least One Prior Systemic Regimen for the Treatment of Stage IIIb/IV SqNSCLC (Checkmate 171)

• ClinicalTrials.gov Identifier: NCT02409368
• Recruitment Status: Completed
• First Posted: April 6, 2015
• Results First Posted: July 29, 2021
• Last Update Posted: November 14, 2022
• Sponsor: Bristol-Myers Squibb
• Collaborator: PPD
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Non-Small Cell Lung Cancer
• Intervention: Drug: Nivolumab
• Enrollment: 812

Participant Flow

Recruitment Details

Pre-assignment Details

1 participant was ECOG PS 3 and thus outside the scope of the protocol and excluded from analysis. There were 2 ECOG classification periods during the course of this study. The population from the first was used in the Primary Outcome Measure analysis. The population from the second was used in the Baseline Characteristics, Secondary Outcome Measures, and Adverse Event analysis. 1 participant was lost from the Primary Completion ECOG Classification that was accounted for at Study Completion.

Arm/Group Title	ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2	ECOG (PS3)
Arm/Group Description	ECOG Performance Status 0 Nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks	ECOG Performance Status 3 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks
Period Title: Original Classification
Started	173	534	103	1
Completed	173	534	103	1
Not Completed	0	0	0	0
Period Title: ECOG Reclassification
Started	172	537	102	1
Completed	0	0	0	0
Not Completed	172	537	102	1
Reason Not Completed
Adverse event unrelated to study drug	17	49	12	0
Death	1	5	0	0
Disease Progression	113	382	70	1
Lost to Follow-up	1	5	0	0
Maximum clinical benefit	6	5	0	0
Poor/non-compliance	0	3	2	0
Study drug toxicity	17	42	7	0
Participant no longer meets study criteria	3	8	3	0
Participant request to discontinue study treatment	6	6	2	0
Participant withdrew consent	2	3	4	0
Other Reasons	5	26	2	0
Administrative reason by sponsor	1	3	0	0

Baseline Characteristics

Arm/Group Title		ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2	ECOG (PS3)	Total
Arm/Group Description		ECOG Performance Status 0 Nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks	ECOG Performance Status 3 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Total of all reporting groups
Overall Number of Baseline Participants		172	537	102	1	812
Baseline Analysis Population Description		Baseline characteristics are listed for all treated participants from the Study Completion ECOG Classification.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	172 participants	537 participants	102 participants	1 participants	812 participants
		63.6 (8.28)	66.1 (8.27)	67.9 (7.29)	71 [1] (NA)	65.8 (8.24)
		[1] Standard deviation not calculated due to insufficient data
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	172 participants	537 participants	102 participants	1 participants	812 participants
	Female	37 21.5%	111 20.7%	22 21.6%	1 100.0%	171 21.1%
	Male	135 78.5%	426 79.3%	80 78.4%	0 0.0%	641 78.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	172 participants	537 participants	102 participants	1 participants	812 participants
	Hispanic or Latino	13 7.6%	37 6.9%	11 10.8%	0 0.0%	61 7.5%
	Not Hispanic or Latino	159 92.4%	500 93.1%	91 89.2%	1 100.0%	751 92.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	172 participants	537 participants	102 participants	1 participants	812 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	2 0.4%	0 0.0%	0 0.0%	2 0.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	3 0.6%	0 0.0%	0 0.0%	3 0.4%
	White	165 95.9%	530 98.7%	102 100.0%	1 100.0%	798 98.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	7 4.1%	2 0.4%	0 0.0%	0 0.0%	9 1.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With High Grade (Grade 3, 4 and 5) Treatment Related Select Adverse Events
Description	The total number of participants with high grade treatment related select adverse events.
Time Frame	From first dose to time of analysis of primary endpoint (approximately up to 34 months)

Outcome Measure Data

Analysis Population Description

All Treated participants

Arm/Group Title	ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:	ECOG Performance Status 0 Nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 Nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed	173	534	103
Measure Type: Count of Participants; Unit of Measure: Participants
Skin	1 0.6%	7 1.3%	0 0.0%
Gastrointestinal	1 0.6%	10 1.9%	0 0.0%
Endocrine	4 2.3%	3 0.6%	0 0.0%
Hepatic	3 1.7%	11 2.1%	2 1.9%
Pulmonary	2 1.2%	5 0.9%	0 0.0%
Renal	0 0.0%	3 0.6%	1 1.0%
Hypersensitivity/ Infusion reaction	0 0.0%	0 0.0%	0 0.0%

2. Secondary Outcome

Title	Number of Participants With High Grade Select Adverse Events
Description	The total number of participants with high grade select adverse events. High grade is defined as Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grades 3-4. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. Select AEs include Pulmonary toxicity, Gastrointestinal toxicity (diarrhea or colitis, Endocrinopathies, Hepatotoxicity (including asymptomatic LFT elevations), Renal toxicity, Skin toxicity, and Neurological toxicity.
Time Frame	From first dose up to 100 days post last dose (up to 76 months)

Outcome Measure Data

Analysis Population Description

All treated participants with ECOG PS Grade 0-2

Arm/Group Title	ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:	ECOG Performance Status 0 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed	172	537	102
Measure Type: Count of Participants; Unit of Measure: Participants
Skin	2 1.2%	7 1.3%	0 0.0%
Gastrointestinal	1 0.6%	11 2.0%	0 0.0%
Endocrine	5 2.9%	4 0.7%	0 0.0%
Hepatic	6 3.5%	19 3.5%	3 2.9%
Pulmonary	3 1.7%	9 1.7%	1 1.0%
Renal	0 0.0%	7 1.3%	1 1.0%
Hypersensitivity/ Infusion reaction	0 0.0%	0 0.0%	1 1.0%

3. Secondary Outcome

Title	Median Time to Onset of Any Grade Select Adverse Events
Description	Median Time to onset of any grade select adverse events reported up to 100 days after last dose. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. Select AEs include Pulmonary toxicity, Gastrointestinal toxicity (diarrhea or colitis, Endocrinopathies, Hepatotoxicity (including asymptomatic LFT elevations), Renal toxicity, Skin toxicity, and Neurological toxicity.
Time Frame	From first dose up to 100 days post last dose (up to approximately 65 months)

Outcome Measure Data

Analysis Population Description

All treated participants with ECOG PS Grade 0-2

Arm/Group Title		ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:		ECOG Performance Status 0 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed		172	537	102
Median (Full Range); Unit of Measure: Weeks
Endrocrine	Number Analyzed	42 participants	62 participants	7 participants
		12.79; (4.0 to 121.6)	10.14; (1.9 to 165.1)	19.86; (6.1 to 55.4)
Gastrointestinal	Number Analyzed	25 participants	101 participants	17 participants
		11.71; (0.1 to 88.0)	8.86; (0.1 to 228.1)	6.00; (0.3 to 64.3)
Hepatic	Number Analyzed	20 participants	58 participants	11 participants
		26.64; (1.4 to 234.1)	11.43; (2.0 to 90.1)	8.14; (2.0 to 88.1)
Pulmonary	Number Analyzed	13 participants	34 participants	4 participants
		33.43; (7.4 to 169.4)	11.50; (0.6 to 166.0)	3.93; (0.1 to 26.3)
Renal	Number Analyzed	13 participants	51 participants	7 participants
		28.86; (4.1 to 129.9)	22.71; (0.1 to 246.0)	10.29; (1.4 to 52.9)
Skin	Number Analyzed	31 participants	132 participants	19 participants
		12.14; (0.1 to 92.1)	7.86; (0.1 to 200.1)	14.71; (2.1 to 81.7)
Hypersensitivity/Infusion Reaction	Number Analyzed	2 participants	12 participants	4 participants
		1.93; (1.7 to 2.1)	2.21; (0.3 to 20.3)	2.14; (2.1 to 28.6)

4. Secondary Outcome

Title	Median Time to Resolution of Any Grade Select Adverse Events
Description	Median time to resolution of any grade select adverse events reported up to 100 days after last dose. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. Select AEs include Pulmonary toxicity, Gastrointestinal toxicity (diarrhea or colitis, Endocrinopathies, Hepatotoxicity (including asymptomatic LFT elevations), Renal toxicity, Skin toxicity, and Neurological toxicity.
Time Frame	From first dose to up to 100 days post last dose (up to approximately 45 months)

Outcome Measure Data

Analysis Population Description

All treated participants with ECOG PS Grade 0-2

Arm/Group Title		ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:		ECOG Performance Status 0 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed		172	537	102
Median (95% Confidence Interval); Unit of Measure: Weeks
Endrocrine	Number Analyzed	42 participants	62 participants	7 participants
		NA [1]; (109.00 to NA)	169.43 [2]; (17.86 to NA)	NA [1]; (6.14 to NA)
Gastrointestinal	Number Analyzed	25 participants	101 participants	17 participants
		2.86; (0.43 to 5.14)	2.00; (1.00 to 3.00)	2.00; (0.43 to 5.71)
Hepatic	Number Analyzed	20 participants	57 participants	11 participants
		4.57; (2.57 to 6.14)	7.71; (4.86 to 17.14)	3.57; (2.14 to 8.14)
Pulmonary	Number Analyzed	13 participants	34 participants	4 participants
		3.00 [2]; (1.43 to NA)	4.29; (2.14 to 6.00)	2.29 [2]; (1.00 to NA)
Renal	Number Analyzed	13 participants	51 participants	7 participants
		10.14 [2]; (2.14 to NA)	6.14; (2.29 to 25.14)	59.14; (0.57 to 59.14)
Skin	Number Analyzed	31 participants	132 participants	19 participants
		NA [1]; (13.57 to NA)	15.43; (8.71 to 52.86)	5.71 [2]; (2.00 to NA)
Hypersensitivity/Infusion Reaction	Number Analyzed	2 participants	12 participants	4 participants
		1.14; (0.14 to 2.14)	0.14; (0.14 to 4.43)	0.14; (0.14 to 0.71)

[1]

Median and upper limit not reached due to insufficient number of events

[2]

Upper limit not reached due to insufficient number of events

5. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) is defined as the time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive. OS will be followed continuously while subjects are on treatment and every 3 months via in-person or phone contact after subjects discontinue the study drug.
Time Frame	From the first dosing up to the date of death (up to approximately 76 months)

Outcome Measure Data

Analysis Population Description

All treated participants with ECOG PS Grade 0-2

Arm/Group Title	ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:	ECOG Performance Status 0 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed	172	537	102
Median (95% Confidence Interval); Unit of Measure: Months
	12.1; (9.9 to 13.4)	10.3; (9.3 to 11.3)	5.2; (3.0 to 7.6)

6. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR is defined as the percentage of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR). CR is defined as the disappearance of all target lesions; PR is defined by at least a 30% decrease in the sum of the longest diameter of target lesions. ORR as assessed by the investigator will be reported.
Time Frame	From first dose up to last dose (up to approximately 76 months)

Outcome Measure Data

Analysis Population Description

All response evaluable participants

Arm/Group Title	ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:	ECOG Performance Status 0 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed	150	456	64
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage
	8.0; (4.2 to 13.6)	11.0; (8.2 to 14.2)	1.6; (0.0 to 8.4)

7. Post-Hoc Outcome

Title	Number of Participants With High Grade (Grade 3, 4 and 5) Treatment Related Select Adverse Events - Extended Collection
Description	The total number of participants with high grade treatment related select adverse events. High grade is defined as Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grades 3-4 or 5. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. Select AEs include Pulmonary toxicity, Gastrointestinal toxicity (diarrhea or colitis, Endocrinopathies, Hepatotoxicity (including asymptomatic LFT elevations), Renal toxicity, Skin toxicity, and Neurological toxicity. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date.
Time Frame	From first dose to up to 100 days post last dose (up to approximately 76 months)

Outcome Measure Data

Analysis Population Description

All treated participants with ECOG PS Grade 0-2

Arm/Group Title	ECOG (PS0)	ECOG (PS1)	ECOG Performance Status 2
Arm/Group Description:	ECOG Performance Status 0 Nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	ECOG Performance Status 1 Nivolumab 3 mg/kg as a 60- minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Number of Participants Analyzed	172	537	102
Measure Type: Count of Participants; Unit of Measure: Participants
Skin	2 1.2%	7 1.3%	0 0.0%
Gastrointestinal	1 0.6%	10 1.9%	0 0.0%
Hepatic	4 2.3%	12 2.2%	2 2.0%
Pulmonary	2 1.2%	6 1.1%	0 0.0%
Renal	0 0.0%	3 0.6%	1 1.0%
Hypersensitivity/ Infusion reaction	0 0.0%	0 0.0%	0 0.0%
Endocrine	4 2.3%	3 0.6%	0 0.0%

Adverse Events

Time Frame	Participants were assessed for all-cause mortality from their enrollment to study completion, (up to approximately 73 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 76 months)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	ECOG Performance Status 0	ECOG Performance Status 1	ECOG Performance Status 2	ECOG Performance Status 3
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
All-Cause Mortality
	ECOG Performance Status 0	ECOG Performance Status 1	ECOG Performance Status 2	ECOG Performance Status 3
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	131/172 (76.16%)	446/537 (83.05%)	90/102 (88.24%)	1/1 (100.00%)
Serious Adverse Events
	ECOG Performance Status 0	ECOG Performance Status 1	ECOG Performance Status 2	ECOG Performance Status 3
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	115/172 (66.86%)	375/537 (69.83%)	84/102 (82.35%)	1/1 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	2/172 (1.16%)	6/537 (1.12%)	1/102 (0.98%)	0/1 (0.00%)
Thrombocytopenia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cardiac disorders
Atrial fibrillation † 1	2/172 (1.16%)	2/537 (0.37%)	2/102 (1.96%)	0/1 (0.00%)
Atrial flutter † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cardiac arrest † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cardiac failure † 1	1/172 (0.58%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Cardiac failure congestive † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cardiac tamponade † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Cardio-respiratory arrest † 1	1/172 (0.58%)	3/537 (0.56%)	1/102 (0.98%)	0/1 (0.00%)
Cardiomegaly † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Intracardiac thrombus † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Left ventricular failure † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Mitral valve prolapse † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Myocardial infarction † 1	2/172 (1.16%)	3/537 (0.56%)	1/102 (0.98%)	0/1 (0.00%)
Pericardial effusion † 1	1/172 (0.58%)	3/537 (0.56%)	1/102 (0.98%)	0/1 (0.00%)
Pericarditis † 1	0/172 (0.00%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Sinus tachycardia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Supraventricular extrasystoles † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	2/172 (1.16%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hypercalcaemia of malignancy † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hyperthyroidism † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Hypophysitis † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Hypothyroidism † 1	2/172 (1.16%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Thyroiditis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Abdominal pain upper † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Anal fissure † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Ascites † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Autoimmune colitis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Colitis † 1	0/172 (0.00%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Colitis microscopic † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Constipation † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Diarrhoea † 1	1/172 (0.58%)	7/537 (1.30%)	1/102 (0.98%)	0/1 (0.00%)
Dysphagia † 1	0/172 (0.00%)	4/537 (0.74%)	1/102 (0.98%)	0/1 (0.00%)
Gastric ulcer † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Gastritis † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Gastrointestinal disorder † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Gastrooesophageal reflux disease † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Immune-mediated enterocolitis † 1	1/172 (0.58%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Inguinal hernia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Intestinal obstruction † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Large intestinal obstruction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Nausea † 1	0/172 (0.00%)	0/537 (0.00%)	0/102 (0.00%)	1/1 (100.00%)
Oesophageal rupture † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Oesophageal stenosis † 1	1/172 (0.58%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Stomatitis † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Vomiting † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
General disorders
Asthenia † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Chest pain † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Death † 1	0/172 (0.00%)	1/537 (0.19%)	1/102 (0.98%)	0/1 (0.00%)
Fatigue † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	1/1 (100.00%)
General physical health deterioration † 1	1/172 (0.58%)	4/537 (0.74%)	1/102 (0.98%)	0/1 (0.00%)
Hernia obstructive † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Non-cardiac chest pain † 1	1/172 (0.58%)	4/537 (0.74%)	1/102 (0.98%)	0/1 (0.00%)
Oedema peripheral † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Pain † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pyrexia † 1	0/172 (0.00%)	8/537 (1.49%)	0/102 (0.00%)	0/1 (0.00%)
Sudden cardiac death † 1	0/172 (0.00%)	1/537 (0.19%)	1/102 (0.98%)	0/1 (0.00%)
Sudden death † 1	1/172 (0.58%)	4/537 (0.74%)	0/102 (0.00%)	0/1 (0.00%)
Systemic inflammatory response syndrome † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/172 (0.00%)	1/537 (0.19%)	2/102 (1.96%)	0/1 (0.00%)
Biliary tract disorder † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cholangitis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Drug-induced liver injury † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Hepatic failure † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hyperbilirubinaemia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Immune-mediated hepatitis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Jaundice † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Jaundice cholestatic † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Liver injury † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Immune system disorders
Drug hypersensitivity † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Infections and infestations
Abscess † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Anal abscess † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Bacteraemia † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Bacterial diarrhoea † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Bacterial infection † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Biliary sepsis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Bronchitis † 1	4/172 (2.33%)	9/537 (1.68%)	1/102 (0.98%)	0/1 (0.00%)
Bronchitis bacterial † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
COVID-19 † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
COVID-19 pneumonia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cellulitis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Clostridium colitis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cystitis † 1	0/172 (0.00%)	0/537 (0.00%)	2/102 (1.96%)	0/1 (0.00%)
H1N1 influenza † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Infection † 1	1/172 (0.58%)	2/537 (0.37%)	1/102 (0.98%)	0/1 (0.00%)
Infective exacerbation of chronic obstructive airways disease † 1	0/172 (0.00%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Lower respiratory tract infection † 1	5/172 (2.91%)	21/537 (3.91%)	5/102 (4.90%)	0/1 (0.00%)
Mediastinitis † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Meningitis aseptic † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Neutropenic sepsis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Parainfluenzae virus infection † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pneumonia † 1	20/172 (11.63%)	41/537 (7.64%)	10/102 (9.80%)	1/1 (100.00%)
Pneumonia bacterial † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pneumonia cytomegaloviral † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pneumonia fungal † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pneumonia pneumococcal † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pulmonary sepsis † 1	1/172 (0.58%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Pulmonary tuberculosis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Respiratory tract infection † 1	11/172 (6.40%)	25/537 (4.66%)	3/102 (2.94%)	0/1 (0.00%)
Sepsis † 1	3/172 (1.74%)	7/537 (1.30%)	0/102 (0.00%)	0/1 (0.00%)
Septic shock † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Staphylococcal infection † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Streptococcal infection † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Tracheobronchitis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Upper respiratory tract infection † 1	1/172 (0.58%)	3/537 (0.56%)	1/102 (0.98%)	0/1 (0.00%)
Urinary tract infection † 1	1/172 (0.58%)	5/537 (0.93%)	1/102 (0.98%)	0/1 (0.00%)
Vulval abscess † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Injury, poisoning and procedural complications
Accidental overdose † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Concussion † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Fall † 1	1/172 (0.58%)	0/537 (0.00%)	2/102 (1.96%)	0/1 (0.00%)
Femur fracture † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Foreign body in gastrointestinal tract † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hip fracture † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Humerus fracture † 1	0/172 (0.00%)	1/537 (0.19%)	1/102 (0.98%)	0/1 (0.00%)
Infusion related reaction † 1	1/172 (0.58%)	1/537 (0.19%)	1/102 (0.98%)	0/1 (0.00%)
Overdose † 1	0/172 (0.00%)	0/537 (0.00%)	2/102 (1.96%)	0/1 (0.00%)
Radiation oesophagitis † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Rib fracture † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Skull fractured base † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Spinal compression fracture † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Splenic rupture † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Subdural haematoma † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Tracheal obstruction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Upper limb fracture † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Investigations
Alanine aminotransferase increased † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Aspartate aminotransferase increased † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Gamma-glutamyltransferase increased † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Liver function test increased † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Metabolism and nutrition disorders
Cachexia † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Decreased appetite † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Dehydration † 1	2/172 (1.16%)	2/537 (0.37%)	1/102 (0.98%)	0/1 (0.00%)
Diabetes mellitus † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Diabetic metabolic decompensation † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hypercalcaemia † 1	1/172 (0.58%)	12/537 (2.23%)	3/102 (2.94%)	0/1 (0.00%)
Hyperglycaemia † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hyperkalaemia † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Hypoalbuminaemia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hypoglycaemia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hypokalaemia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hyponatraemia † 1	2/172 (1.16%)	3/537 (0.56%)	2/102 (1.96%)	0/1 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Arthritis † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Back pain † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Bone pain † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Muscular weakness † 1	1/172 (0.58%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Musculoskeletal chest pain † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Osteonecrosis † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Pain in extremity † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Patellofemoral pain syndrome † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pathological fracture † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Spinal pain † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Bladder cancer † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Bladder neoplasm † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Brain cancer metastatic † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cancer pain † 1	3/172 (1.74%)	2/537 (0.37%)	1/102 (0.98%)	0/1 (0.00%)
Colon cancer † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Follicular thyroid cancer † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Lung neoplasm malignant † 1	0/172 (0.00%)	1/537 (0.19%)	1/102 (0.98%)	0/1 (0.00%)
Malignant neoplasm progression † 1	59/172 (34.30%)	206/537 (38.36%)	58/102 (56.86%)	0/1 (0.00%)
Metastases to central nervous system † 1	0/172 (0.00%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Metastases to lymph nodes † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Non-small cell lung cancer metastatic † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Oncologic complication † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pancreatic carcinoma † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Small intestine adenocarcinoma † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Tumour associated fever † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Tumour compression † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Tumour pain † 1	1/172 (0.58%)	5/537 (0.93%)	2/102 (1.96%)	0/1 (0.00%)
Nervous system disorders
Brain oedema † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Cerebral haemorrhage † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cerebral infarction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Cerebrovascular accident † 1	1/172 (0.58%)	2/537 (0.37%)	1/102 (0.98%)	0/1 (0.00%)
Coma † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Dizziness † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Epilepsy † 1	1/172 (0.58%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Intracranial pressure increased † 1	2/172 (1.16%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Lacunar infarction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Loss of consciousness † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Monoparesis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Motor dysfunction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Neuropathy peripheral † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Peripheral sensory neuropathy † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Seizure † 1	1/172 (0.58%)	3/537 (0.56%)	0/102 (0.00%)	0/1 (0.00%)
Spinal cord compression † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Status epilepticus † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Syncope † 1	0/172 (0.00%)	0/537 (0.00%)	3/102 (2.94%)	0/1 (0.00%)
Transient ischaemic attack † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Tremor † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Psychiatric disorders
Agitation † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Confusional state † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Delirium † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Mania † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	0/172 (0.00%)	4/537 (0.74%)	1/102 (0.98%)	0/1 (0.00%)
Calculus urinary † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Leukocyturia † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Nephrolithiasis † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Renal failure † 1	0/172 (0.00%)	4/537 (0.74%)	0/102 (0.00%)	0/1 (0.00%)
Urinary retention † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Urinary tract obstruction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/172 (0.00%)	2/537 (0.37%)	2/102 (1.96%)	0/1 (0.00%)
Aspiration † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Asthma † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Atelectasis † 1	2/172 (1.16%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Bronchial obstruction † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Bronchopneumopathy † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Chronic obstructive pulmonary disease † 1	1/172 (0.58%)	7/537 (1.30%)	5/102 (4.90%)	0/1 (0.00%)
Dyspnoea † 1	9/172 (5.23%)	28/537 (5.21%)	10/102 (9.80%)	1/1 (100.00%)
Epistaxis † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Haemoptysis † 1	7/172 (4.07%)	11/537 (2.05%)	3/102 (2.94%)	0/1 (0.00%)
Hypoxia † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Immune-mediated lung disease † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Interstitial lung disease † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Lung consolidation † 1	0/172 (0.00%)	0/537 (0.00%)	1/102 (0.98%)	0/1 (0.00%)
Oesophagobronchial fistula † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Pleural effusion † 1	3/172 (1.74%)	10/537 (1.86%)	2/102 (1.96%)	1/1 (100.00%)
Pneumonia aspiration † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Pneumonitis † 1	4/172 (2.33%)	15/537 (2.79%)	0/102 (0.00%)	0/1 (0.00%)
Pneumothorax † 1	0/172 (0.00%)	2/537 (0.37%)	1/102 (0.98%)	0/1 (0.00%)
Pulmonary embolism † 1	3/172 (1.74%)	6/537 (1.12%)	0/102 (0.00%)	0/1 (0.00%)
Pulmonary haemorrhage † 1	1/172 (0.58%)	2/537 (0.37%)	1/102 (0.98%)	0/1 (0.00%)
Respiratory failure † 1	3/172 (1.74%)	10/537 (1.86%)	1/102 (0.98%)	0/1 (0.00%)
Respiratory tract haemorrhage † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
Tracheal stenosis † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Rash macular † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	0/172 (0.00%)	1/537 (0.19%)	1/102 (0.98%)	0/1 (0.00%)
Embolism † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hypertension † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Hypotension † 1	1/172 (0.58%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Peripheral ischaemia † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	0/1 (0.00%)
Superior vena cava occlusion † 1	1/172 (0.58%)	2/537 (0.37%)	0/102 (0.00%)	0/1 (0.00%)
Superior vena cava syndrome † 1	0/172 (0.00%)	4/537 (0.74%)	0/102 (0.00%)	0/1 (0.00%)
Venous thrombosis limb † 1	1/172 (0.58%)	0/537 (0.00%)	0/102 (0.00%)	0/1 (0.00%)
1 Term from vocabulary, 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	ECOG Performance Status 0	ECOG Performance Status 1	ECOG Performance Status 2	ECOG Performance Status 3
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	149/172 (86.63%)	472/537 (87.90%)	86/102 (84.31%)	1/1 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	23/172 (13.37%)	97/537 (18.06%)	21/102 (20.59%)	1/1 (100.00%)
Endocrine disorders
Hypothyroidism † 1	25/172 (14.53%)	37/537 (6.89%)	6/102 (5.88%)	0/1 (0.00%)
Hyperthyroidism † 1	13/172 (7.56%)	18/537 (3.35%)	1/102 (0.98%)	0/1 (0.00%)
Eye disorders
Lacrimation increased † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	1/1 (100.00%)
Gastrointestinal disorders
Constipation † 1	18/172 (10.47%)	80/537 (14.90%)	16/102 (15.69%)	0/1 (0.00%)
Diarrhoea † 1	26/172 (15.12%)	100/537 (18.62%)	16/102 (15.69%)	0/1 (0.00%)
Nausea † 1	20/172 (11.63%)	71/537 (13.22%)	16/102 (15.69%)	0/1 (0.00%)
Vomiting † 1	9/172 (5.23%)	34/537 (6.33%)	9/102 (8.82%)	1/1 (100.00%)
Abdominal pain † 1	2/172 (1.16%)	28/537 (5.21%)	3/102 (2.94%)	0/1 (0.00%)
Stomatitis † 1	5/172 (2.91%)	14/537 (2.61%)	7/102 (6.86%)	0/1 (0.00%)
General disorders
Asthenia † 1	30/172 (17.44%)	131/537 (24.39%)	15/102 (14.71%)	0/1 (0.00%)
Fatigue † 1	40/172 (23.26%)	121/537 (22.53%)	25/102 (24.51%)	1/1 (100.00%)
Non-cardiac chest pain † 1	6/172 (3.49%)	34/537 (6.33%)	5/102 (4.90%)	0/1 (0.00%)
Oedema peripheral † 1	7/172 (4.07%)	30/537 (5.59%)	14/102 (13.73%)	1/1 (100.00%)
Pyrexia † 1	9/172 (5.23%)	49/537 (9.12%)	8/102 (7.84%)	0/1 (0.00%)
Chest pain † 1	10/172 (5.81%)	24/537 (4.47%)	1/102 (0.98%)	0/1 (0.00%)
Influenza like illness † 1	3/172 (1.74%)	4/537 (0.74%)	2/102 (1.96%)	1/1 (100.00%)
Peripheral swelling † 1	2/172 (1.16%)	8/537 (1.49%)	2/102 (1.96%)	1/1 (100.00%)
Infections and infestations
Lower respiratory tract infection † 1	18/172 (10.47%)	51/537 (9.50%)	7/102 (6.86%)	0/1 (0.00%)
Respiratory tract infection † 1	10/172 (5.81%)	37/537 (6.89%)	6/102 (5.88%)	0/1 (0.00%)
Upper respiratory tract infection † 1	10/172 (5.81%)	29/537 (5.40%)	2/102 (1.96%)	0/1 (0.00%)
Catheter site infection † 1	0/172 (0.00%)	0/537 (0.00%)	0/102 (0.00%)	1/1 (100.00%)
Nasopharyngitis † 1	11/172 (6.40%)	15/537 (2.79%)	1/102 (0.98%)	0/1 (0.00%)
Oral candidiasis † 1	4/172 (2.33%)	26/537 (4.84%)	3/102 (2.94%)	1/1 (100.00%)
Oral fungal infection † 1	0/172 (0.00%)	1/537 (0.19%)	0/102 (0.00%)	1/1 (100.00%)
Pneumonia † 1	11/172 (6.40%)	24/537 (4.47%)	5/102 (4.90%)	0/1 (0.00%)
Tooth infection † 1	2/172 (1.16%)	1/537 (0.19%)	0/102 (0.00%)	1/1 (100.00%)
Investigations
Alanine aminotransferase increased † 1	12/172 (6.98%)	30/537 (5.59%)	5/102 (4.90%)	0/1 (0.00%)
Aspartate aminotransferase increased † 1	15/172 (8.72%)	28/537 (5.21%)	5/102 (4.90%)	0/1 (0.00%)
Blood creatinine increased † 1	9/172 (5.23%)	34/537 (6.33%)	5/102 (4.90%)	0/1 (0.00%)
Weight decreased † 1	8/172 (4.65%)	42/537 (7.82%)	7/102 (6.86%)	0/1 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	24/172 (13.95%)	147/537 (27.37%)	24/102 (23.53%)	0/1 (0.00%)
Hypercalcaemia † 1	6/172 (3.49%)	39/537 (7.26%)	6/102 (5.88%)	0/1 (0.00%)
Hypomagnesaemia † 1	11/172 (6.40%)	27/537 (5.03%)	5/102 (4.90%)	0/1 (0.00%)
Hyperkalaemia † 1	7/172 (4.07%)	20/537 (3.72%)	6/102 (5.88%)	0/1 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	24/172 (13.95%)	52/537 (9.68%)	7/102 (6.86%)	1/1 (100.00%)
Back pain † 1	11/172 (6.40%)	46/537 (8.57%)	7/102 (6.86%)	1/1 (100.00%)
Groin pain † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	1/1 (100.00%)
Musculoskeletal chest pain † 1	7/172 (4.07%)	24/537 (4.47%)	7/102 (6.86%)	0/1 (0.00%)
Pain in extremity † 1	4/172 (2.33%)	25/537 (4.66%)	6/102 (5.88%)	1/1 (100.00%)
Nervous system disorders
Headache † 1	10/172 (5.81%)	36/537 (6.70%)	3/102 (2.94%)	0/1 (0.00%)
Dizziness † 1	3/172 (1.74%)	28/537 (5.21%)	8/102 (7.84%)	0/1 (0.00%)
Seizure † 1	0/172 (0.00%)	2/537 (0.37%)	0/102 (0.00%)	1/1 (100.00%)
Psychiatric disorders
Anxiety † 1	9/172 (5.23%)	12/537 (2.23%)	1/102 (0.98%)	0/1 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	44/172 (25.58%)	134/537 (24.95%)	19/102 (18.63%)	0/1 (0.00%)
Dyspnoea † 1	44/172 (25.58%)	167/537 (31.10%)	28/102 (27.45%)	1/1 (100.00%)
Haemoptysis † 1	11/172 (6.40%)	47/537 (8.75%)	10/102 (9.80%)	0/1 (0.00%)
Pleural effusion † 1	2/172 (1.16%)	6/537 (1.12%)	1/102 (0.98%)	1/1 (100.00%)
Pneumonitis † 1	10/172 (5.81%)	22/537 (4.10%)	2/102 (1.96%)	0/1 (0.00%)
Productive cough † 1	3/172 (1.74%)	26/537 (4.84%)	6/102 (5.88%)	0/1 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus † 1	9/172 (5.23%)	58/537 (10.80%)	10/102 (9.80%)	0/1 (0.00%)
Rash † 1	10/172 (5.81%)	39/537 (7.26%)	5/102 (4.90%)	0/1 (0.00%)
Dry skin † 1	7/172 (4.07%)	26/537 (4.84%)	6/102 (5.88%)	0/1 (0.00%)
Vascular disorders
Hypertension † 1	12/172 (6.98%)	19/537 (3.54%)	0/102 (0.00%)	0/1 (0.00%)
1 Term from vocabulary, 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please Email
• EMail: Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Felip E, Ardizzoni A, Ciuleanu T, Cobo M, Laktionov K, Szilasi M, Califano R, Carcereny E, Griffiths R, Paz-Ares L, Duchnowska R, Garcia MA, Isla D, Jassem J, Appel W, Milanowski J, Van Meerbeeck JP, Wolf J, Li A, Acevedo A, Popat S. CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations. Eur J Cancer. 2020 Mar;127:160-172. doi: 10.1016/j.ejca.2019.11.019. Epub 2020 Feb 3.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02409368
• Other Study ID Numbers: CA209-171; 2014-001285-10 ( EudraCT Number )
• First Submitted: April 1, 2015
• First Posted: April 6, 2015
• Results First Submitted: March 31, 2021
• Results First Posted: July 29, 2021
• Last Update Posted: November 14, 2022