A Single-Arm, Open-Label, Multicenter Clinical Trial With Nivolumab (BMS-936558) for Subjects With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma Progressing Post Prior Treatment Containing an Anti-CTLA4 Monoclonal Antibody (CheckMate 172)

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02156804
• Collaborator: (none)
• Enrollment: 1,009
• Locations: 170
• Arm: 1
• Actual Duration (Months): 51.4
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the rate and frequency of high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-Cytotoxic T Lymphocyte Antigen (CTLA-4) monoclonal antibody, treated with Nivolumab (BMS-936558) at a dose of 3 mg/kg every two weeks.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Nivolumab (BMS-936558)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1009 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Open-Label, Multicenter Clinical Trial With Nivolumab (BMS-936558) for Subjects With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma Progressing Post Prior Treatment Containing an Anti-CTLA4 Monoclonal Antibody
• Actual Study Start Date: Oct 7, 2014
• Actual Primary Completion Date: Jan 18, 2019
• Actual Study Completion Date: Jan 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab (BMS-936558) Nivolumab (BMS-936558) Intravenous solution every 2 weeks	Drug: Nivolumab (BMS-936558)

Outcome Measures

Primary Outcome Measures

1. the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events. [Up to 2 years]

   The number of participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select AEs (pulmonary,gastrointestinal, skin, renal, hepatic, endocrine) were summarized using the all treated analysis set by system organ class and Medical Dictionary for Regulatory (MedDRA) preferred term.

Secondary Outcome Measures

1. The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events [Up to 2 years]

   The number of Participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), select AEs were summarized using the all treated analysis set by system organ class and MedDRA preferred term.

2. Median Time to Onset (Grades 3-4) of Select Adverse Events [Up to 2 years.]

   Select AEs were summarized according to their incidence as well as their time to onset.

3. Median Time to Resolution (Grades 3-4) of Select Adverse Events [Up to 2 years]

   Select AEs were summarized according to their incidence as well as their time to resolution

4. Overall Survival [Up to 4 years]

   The time from first dosing date to the date of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects with histologically confirmed malignant melanoma

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS):

• PS 0 to 1

• PS 2

• Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines regardless of BRAF mutation status

• Subjects must have experienced evaluable Response Evaluation Criteria In Solid Tumors (RECIST 1.1)-defined disease progression

• Prior treatment with chemotherapy, interferon (adjuvant setting), Interleukin (IL-2), BRAF/MEK inhibitors for subjects with known BRAF mutations, Mitogen-activated or extracellular signal- regulated protein kinase (MEK) inhibitors for Neuroblastoma Ras Viral (v-ras) oncogene homolog (NRAS) mutations, and cKIT inhibitor subjects with known cKIT mutations are allowed

• Patients with CNS metastases are eligible:

• if CNS metastases are treated, patients are asymptomatic or neurologically returned to baseline

• if they have previously untreated CNS metastases and are asymptomatic

• if they have leptomeningeal metastases, are treated and asymptomatic or neurologically returned to baseline with life expectancy > 3 months

• Patients with a known history of Grades 3-4 immune-related adverse reactions during/after anti-CTLA-4 therapy if all toxicities have resolved at least to Grade 1

Exclusion Criteria:

• Subjects with untreated, active Central Nervous System (CNS) metastases are excluded

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Graz		Austria	8036
2	Local Institution	Innsbruck		Austria	6020
3	Local Institution	Salzburg		Austria	5020
4	Local Institution	St. Polten		Austria	3100
5	Local Institution	Wein		Austria	1090
6	Local Institution	Wien		Austria	1030
7	Universitair Ziekenhuis Brussel	Brussels		Belgium	1090
8	Institut Jules Bordet	Bruxelles		Belgium	1000
9	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
10	Local Institution	Edegem		Belgium	2650
11	Local Institution	Gent		Belgium	9000
12	Local Institution	Hasselt		Belgium	3500
13	Az Groeninge	Kortrijk		Belgium	8500
14	Local Institution	Leuven		Belgium	3000
15	Chu De Liege	Liege		Belgium	4000
16	Local Institution	Brno		Czechia	656 53
17	Local Institution	Hradec Kralove		Czechia	500 05
18	Local Institution	Praha 10		Czechia	100 34
19	Local Institution	Praha 2		Czechia	120 28
20	Local Institution	Helsinki		Finland	00290
21	Local Institution	Jyvaskyla		Finland	40620
22	Local Institution	Oulu		Finland	90220
23	Local Institution	Tampere		Finland	33520
24	Local Institution	Luebeck	Schleswig-holstein	Germany	23538
25	Local Institution	Augsburg		Germany	86156
26	Local Institution	Bochum		Germany	44791
27	Local Institution	Buxtehude		Germany	21614
28	Local Institution	Chemnitz		Germany	09117
29	Local Institution	Dessau		Germany	06847
30	Local Institution	Dresden		Germany	01307
31	Local Institution	Erfurt		Germany	99089
32	Local Institution	Erlangen		Germany	91054
33	Local Institution	Essen		Germany	45 122
34	Local Institution	Frankfurt Am Main		Germany	60590
35	Local Institution	Freiburg		Germany	79104
36	Local Institution	Gera		Germany	07548
37	Local Institution	Giessen		Germany	35385
38	Local Institution	Goettingen		Germany	37075
39	Local Institution	Hamburg		Germany	20253
40	Local Institution	Hannover		Germany	30625
41	Local Institution	Heidelberg		Germany	69120
42	Local Institution	Heilbronn		Germany	74078
43	Local Institution	Jena		Germany	07740
44	Local Institution	Kassel		Germany	34125
45	Local Institution	Kiel		Germany	24105
46	Local Institution	Koln		Germany	50937
47	Local Institution	Leipzig		Germany	04103
48	Local Institution	Ludwigshafen		Germany	67063
49	Local Institution	Magdeburg		Germany	39120
50	Local Institution	Mainz		Germany	55131
51	Local Institution	Marburg		Germany	35043
52	Local Institution	Minden		Germany	32429
53	Local Institution	Muenster		Germany	48149
54	Local Institution	Munchen		Germany	80337
55	Local Institution	Munchen		Germany	81675
56	Local Institution	Munster		Germany	48157
57	Local Institution	Nuernberg		Germany	90419
58	Local Institution	Quedlinburg		Germany	06484
59	Local Institution	Recklinghausen		Germany	45657
60	Local Institution	Regensburg		Germany	93053
61	Local Institution	Schwerin		Germany	19049
62	Local Institution	Traunstein		Germany	83278
63	Local Institution	Tubingen		Germany	72076
64	Local Institution	Wurzbug		Germany	97080
65	Local Institution	Heraklion	Creta	Greece	71201
66	Local Institution	Athens		Greece	11527
67	Local Institution	Athens		Greece	18547
68	Local Institution	Thessaloniki		Greece	54007
69	Local Institution	Thessaloniki		Greece	57010
70	Local Institution	Budapest		Hungary	1122
71	Local Institution	Budapest		Hungary	H-7085
72	Local Institution	Debrecen		Hungary	4032
73	Local Institution	Pecs		Hungary	H-7632
74	Local Institution	Szeged		Hungary	H-6720
75	Local Institution	Szombathely		Hungary	9700
76	Local Institution	Wilton	Cork	Ireland
77	Local Institution	Dublin		Ireland	4
78	Local Institution	Dublin		Ireland	7
79	Local Institution	Dublin		Ireland	8
80	Local Institution	Dublin		Ireland	9
81	Local Institution	Galway		Ireland
82	Local Institution	Waterford		Ireland	9026
83	Local Institution	Bari		Italy	70124
84	Local Institution	Bergamo		Italy	24127
85	Local Institution	Genova		Italy	16132
86	Local Institution	Meldola (FC)		Italy	47014
87	Local Institution	Milano		Italy	20132
88	Local Institution	Milano		Italy	20133
89	Local Institution	Milano		Italy	20141
90	Local Institution	Napoli		Italy	80131
91	Local Institution	Padova		Italy	35128
92	Local Institution	Palermo		Italy	90127
93	Local Institution	Roma		Italy	00144
94	Local Institution	Roma		Italy	00167
95	Local Institution	Siena		Italy	53100
96	Local Institution	Terni		Italy	05100
97	Local Institution	Torino		Italy	10137
98	Local Institution	Luxembourg		Luxembourg	1210
99	Local Institution	Amsterdam	Noord-holland	Netherlands	1081 HZ
100	Local Institution	Amsterdam		Netherlands	1066 CX
101	Local Institution	Breda		Netherlands	4918 EV
102	Local Institution	Enschede		Netherlands	7513 ER
103	Local Institution	Groningen		Netherlands	9713 GZ
104	Local Institution	Leeuwarden		Netherlands	8934 AD
105	Local Institution	Leiden		Netherlands	2300 RC
106	Local Institution	Maastrict		Netherlands	6229 HX
107	Local Institution	Nijmegen		Netherlands	6525 GA
108	Local Institution	Rotterdam		Netherlands	3075 EA
109	Local Institution	Sittard-Geleen		Netherlands	6162 BG
110	Local Institution	Utrecht		Netherlands	3584 CX
111	Local Institution	Veldhoven		Netherlands	5504 DB
112	Local Institution	Zwolle		Netherlands	8025-AB
113	Local Institution	Alesund		Norway	6017
114	Local Institution	Bergen		Norway	5021
115	Local Institution	Oslo		Norway	0310
116	Local Institution	Bydgoszcz		Poland	85-796
117	Local Institution	Gdansk		Poland	80-952
118	Local Institution	Lodz		Poland	93-513
119	Local Institution	Warszawa		Poland	02781
120	Local Institution	Lisboa		Portugal	1099-023
121	Local Institution	Porto		Portugal	4200-072
122	Local Institution	Bucharest		Romania	022328
123	Local Institution	Romania		Romania	400015
124	Local Institution	Moscow		Russian Federation	115478
125	Local Institution	St. Petersburg		Russian Federation	197022
126	Local Institution	St. Petersburg		Russian Federation	197758
127	Local Institution	Albacete		Spain	02006
128	Local Institution	Barcelona		Spain	08035
129	Local Institution	Barcelona		Spain	08036
130	Local Institution	Barcelona		Spain	08908
131	Local Institution	Bilbao		Spain	48013
132	Local Institution	Granada		Spain	18014
133	Local Institution	Las Palmas de Gran Canaria		Spain	35016
134	Local Institution	Madrid		Spain	28007
135	Local Institution	Madrid		Spain	28041
136	Local Institution	Madrid		Spain	28046
137	Hospital De Madrid, Norte Sanchinarro	Madrid		Spain	28050
138	Local Institution	Malaga		Spain	29010
139	Local Institution	Oviedo		Spain	33011
140	Local Institution	Palma de Mallorca		Spain	07010
141	Local Institution	Salamanca		Spain	37007
142	Local Institution	San Sebastian		Spain	20014
143	Hospital Clinico Univ. de Santiago-CHUS	Santiago de Compostela		Spain	15706
144	Local Institution	Sevilla		Spain	41071
145	Local Institution	Toledo		Spain	45071
146	Local Institution	Valencia		Spain	46009
147	Local Institution	Valencia		Spain	46026
148	Local Institution	Lund		Sweden	221 85
149	Local Institution	Uppsala		Sweden	751 85
150	Local Institution	Aarau		Switzerland	5001
151	Local Institution	Basel		Switzerland	4031
152	Local Institution	Bellinzona		Switzerland	6501
153	Local Institution	Chur		Switzerland	7000
154	Local Institution	Zurich		Switzerland	8091
155	Local Institution	Bristol	Avon	United Kingdom	BS2 8ED
156	Local Institution	Northwood	Middlesex	United Kingdom	HA6 2RN
157	Local Institution	Birmingham		United Kingdom	B15 2TH
158	Local Institution	Cambridge		United Kingdom	CB2 0QQ
159	Local Institution	Cottingham		United Kingdom	HU16 5JQ
160	Local Institution	Essex		United Kingdom
161	Local Institution	Glasgow		United Kingdom	G12 0YN
162	Local Institution	London		United Kingdom	SE1 9RT
163	Local Institution	Manchester		United Kingdom	M20 4BX
164	Local Institution	Newcastle Upon Tyne		United Kingdom	NE7 7DN
165	Local Institution	Oxford		United Kingdom	OX3 7LE
166	Local Institution	Southampton		United Kingdom	SO16 6YD
167	Local Institution	Surrey		United Kingdom	SM2 5PT
168	Local Institution	Swansea		United Kingdom	SA2 8QA
169	Local Institution	Truro		United Kingdom	TR1 3LJ
170	Local Institution	Wirral		United Kingdom	CH63 4JY

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 13, 2019
• Study Protocol - Nov 17, 2017

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02156804
• Other Study ID Numbers: CA209-172; 2014-001286-28
• First Posted: Jun 5, 2014
• Last Update Posted: Sep 11, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Melanoma; Nivolumab

Study Results

Participant Flow

Pre-assignment Detail	1009 participants were enrolled into the study , 1008 wrere treated, 1 participants was not treated due to withdrew consent

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Period Title: Overall Study
STARTED	1009
COMPLETED	1008
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Overall Participants	1008
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.1 (13.84)
Sex: Female, Male (Count of Participants)
Female	451 44.7%
Male	557 55.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	27 2.7%
Not Hispanic or Latino	972 96.4%
Unknown or Not Reported	9 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 0.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 0.3%
White	987 97.9%
More than one race	0 0%
Unknown or Not Reported	15 1.5%

Outcome Measures

1. Primary Outcome

Title	the Incidence of Highgrade (CTCAE v4.0 Grade 3 or Higher), Treatment Related,Select Adverse Events.
Description	The number of participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select AEs (pulmonary,gastrointestinal, skin, renal, hepatic, endocrine) were summarized using the all treated analysis set by system organ class and Medical Dictionary for Regulatory (MedDRA) preferred term.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Measure Participants	1008
Gastrointestinal Adverse events (Grade 3-4)	16 1.6%
Gastrointestinal adverse events (Grade 5)	0 0%
Hepatic adverse events (Grade 3-4)	30 3%
Hepatic adverse events (Grade 5)	0 0%
Pulmonary adverse events(Grade 3-4)	6 0.6%
Pulmonary adverse events(Grade 5)	0 0%
Renal adverse events (Grade 3-4)	4 0.4%
Renal adverse events (Grade 5)	0 0%
Skin adverse events ( Grade 3-4)	13 1.3%
Skin adverse events ( Grade 5)	0 0%
Hypersensitivity adverse event( Grade 3-4)	1 0.1%
Hypersensitivity adverse event( Grade 5)	0 0%
Endocrine adverse events(Grade 3-4)	18 1.8%
Endocrine adverse events(Grade 5)	0 0%

2. Secondary Outcome

Title	The Incidence of All High-grade (Grades 3 and Higher), Select Adverse Events
Description	The number of Participants who reported high-grade (CTCAE v4.0 Grade 3 or higher), select AEs were summarized using the all treated analysis set by system organ class and MedDRA preferred term.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All treated Participants

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Measure Participants	1008
Gastrointestinal Adverse events (Grade 3-4)	24 2.4%
Gastrointestinal adverse events (Grade 5)	0 0%
Hepatic adverse events (Grade 3-4)	52 5.2%
Hepatic adverse events (Grade 5)	1 0.1%
Pulmonary adverse events(Grade 3-4)	7 0.7%
Pulmonary adverse events(Grade 5)	1 0.1%
Renal adverse events (Grade 3-4)	12 1.2%
Renal adverse events (Grade 5)	1 0.1%
Skin adverse events ( Grade 3-4)	19 1.9%
Skin adverse events ( Grade 5)	0 0%
Hypersensitivity adverse event( Grade 3-4)	2 0.2%
Hypersensitivity adverse event( Grade 5)	0 0%
Endocrine adverse events(Grade 3-4)	24 2.4%
Endocrine adverse events(Grade 5)	0 0%

3. Secondary Outcome

Title	Median Time to Onset (Grades 3-4) of Select Adverse Events
Description	Select AEs were summarized according to their incidence as well as their time to onset.
Time Frame	Up to 2 years.

Outcome Measure Data

Analysis Population Description

All Treated Participants.

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Measure Participants	1008
Endocrine Adverse Events	12
Gastrointestinal Adverse Events	23.50
Hepatic Adverse Events	10.14
Pulmonary Adverse Events	14.86
Renal Adverse Events	11.71
Skin Adverse Events	34.36
Hypersensitivity/infusion reaction Adverse Events	29.57

4. Secondary Outcome

Title	Median Time to Resolution (Grades 3-4) of Select Adverse Events
Description	Select AEs were summarized according to their incidence as well as their time to resolution
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Measure Participants	1008
Endocrine Adverse Events	2.43
Gastrointestinal Adverse Events	3.71
Hepatic Adverse Events	9.43
Pulmonary Adverse Events	2.57
Renal Adverse Events	1.93
Skin Adverse Events	5.07
Hypersensitivity/infusion reaction Adverse Events	0.29

5. Secondary Outcome

Title	Overall Survival
Description	The time from first dosing date to the date of death.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
Measure Participants	1008
Median (95% Confidence Interval) [Months]	21.2

Adverse Events

Time Frame	Between first dose and 30 days after last dose ( up to 2 years)
Arm/Group Title	NIVOLUMAB 3 MG/KG IV
Arm/Group Description	Nivolumab 3 mg/kg as a 60-minute IV infusion every 2 weeks
All Cause Mortality
	NIVOLUMAB 3 MG/KG IV
	Affected / at Risk (%)	# Events
Total	527/1008 (52.3%)
Serious Adverse Events
	NIVOLUMAB 3 MG/KG IV
	Affected / at Risk (%)	# Events
Total	593/1008 (58.8%)
Blood and lymphatic system disorders
Anaemia	10/1008 (1%)
Haemorrhagic anaemia	1/1008 (0.1%)
Thrombocytopenia	1/1008 (0.1%)
Cardiac disorders
Acute coronary syndrome	2/1008 (0.2%)
Acute myocardial infarction	1/1008 (0.1%)
Angina pectoris	2/1008 (0.2%)
Atrial fibrillation	3/1008 (0.3%)
Atrial flutter	1/1008 (0.1%)
Cardiac failure	1/1008 (0.1%)
Cardiopulmonary failure	1/1008 (0.1%)
Coronary artery occlusion	1/1008 (0.1%)
Ischaemic cardiomyopathy	1/1008 (0.1%)
Myocardial infarction	2/1008 (0.2%)
Myocarditis	1/1008 (0.1%)
Pericardial effusion	1/1008 (0.1%)
Cardio-respiratory arrest	1/1008 (0.1%)
Coronary artery disease	1/1008 (0.1%)
Coronary artery insufficiency	1/1008 (0.1%)
Supraventricular tachycardia	1/1008 (0.1%)
Ear and labyrinth disorders
Vertigo	2/1008 (0.2%)
Endocrine disorders
Addison's disease	1/1008 (0.1%)
Adrenal insufficiency	5/1008 (0.5%)
Autoimmune thyroiditis	2/1008 (0.2%)
Hyperthyroidism	1/1008 (0.1%)
Hypophysitis	4/1008 (0.4%)
Hypopituitarism	3/1008 (0.3%)
Hypothyroidism	3/1008 (0.3%)
Lymphocytic hypophysitis	1/1008 (0.1%)
Secondary adrenocortical insufficiency	1/1008 (0.1%)
Steroid withdrawal syndrome	1/1008 (0.1%)
Adrenal haemorrhage	1/1008 (0.1%)
Eye disorders
Ectropion	1/1008 (0.1%)
Iridocyclitis	1/1008 (0.1%)
Iritis	1/1008 (0.1%)
Macular hole	1/1008 (0.1%)
Ulcerative keratitis	1/1008 (0.1%)
Uveitis	1/1008 (0.1%)
Vision blurred	1/1008 (0.1%)
Retinal detachment	1/1008 (0.1%)
Vitreous haemorrhage	1/1008 (0.1%)
Gastrointestinal disorders
Abdominal pain	13/1008 (1.3%)
Ascites	5/1008 (0.5%)
Autoimmune colitis	3/1008 (0.3%)
Autoimmune pancreatitis	1/1008 (0.1%)
Colitis	7/1008 (0.7%)
Colitis ischaemic	1/1008 (0.1%)
Constipation	2/1008 (0.2%)
Diarrhoea	14/1008 (1.4%)
Dyspepsia	1/1008 (0.1%)
Food poisoning	1/1008 (0.1%)
Gastritis	3/1008 (0.3%)
Gastrointestinal haemorrhage	2/1008 (0.2%)
Ileal perforation	1/1008 (0.1%)
Inguinal hernia	2/1008 (0.2%)
Intestinal fistula	1/1008 (0.1%)
Intestinal obstruction	4/1008 (0.4%)
Intussusception	2/1008 (0.2%)
Large intestinal obstruction	1/1008 (0.1%)
Melaena	3/1008 (0.3%)
Nausea	8/1008 (0.8%)
Oesophagitis	1/1008 (0.1%)
Pancreatitis	1/1008 (0.1%)
Pancreatitis acute	1/1008 (0.1%)
Rectal haemorrhage	2/1008 (0.2%)
Small intestinal obstruction	1/1008 (0.1%)
Small intestinal perforation	1/1008 (0.1%)
Stomatitis	1/1008 (0.1%)
Upper gastrointestinal haemorrhage	1/1008 (0.1%)
Vomiting	10/1008 (1%)
Anal haemorrhage	1/1008 (0.1%)
Gastrointestinal disorder	1/1008 (0.1%)
Gastrooesophageal reflux disease	1/1008 (0.1%)
Ileus	1/1008 (0.1%)
Subileus	1/1008 (0.1%)
General disorders
Asthenia	5/1008 (0.5%)
Chest pain	2/1008 (0.2%)
Disease progression	2/1008 (0.2%)
Fatigue	7/1008 (0.7%)
General physical health deterioration	22/1008 (2.2%)
Generalised oedema	1/1008 (0.1%)
Malaise	3/1008 (0.3%)
Nodule	1/1008 (0.1%)
Oedema peripheral	4/1008 (0.4%)
Pyrexia	9/1008 (0.9%)
Sudden death	3/1008 (0.3%)
Treatment failure	1/1008 (0.1%)
Multiple organ dysfunction syndrome	2/1008 (0.2%)
Pain	1/1008 (0.1%)
Hepatobiliary disorders
Autoimmune hepatitis	8/1008 (0.8%)
Cholecystitis	1/1008 (0.1%)
Cholelithiasis	2/1008 (0.2%)
Hepatic failure	1/1008 (0.1%)
Hepatic function abnormal	1/1008 (0.1%)
Hepatic pain	3/1008 (0.3%)
Hepatomegaly	1/1008 (0.1%)
Hypertransaminasaemia	1/1008 (0.1%)
Immune-mediated hepatitis	4/1008 (0.4%)
Jaundice	2/1008 (0.2%)
Jaundice cholestatic	1/1008 (0.1%)
Liver disorder	1/1008 (0.1%)
Immune system disorders
Anaphylactic shock	1/1008 (0.1%)
Autoimmune disorder	1/1008 (0.1%)
Contrast media allergy	2/1008 (0.2%)
Drug hypersensitivity	1/1008 (0.1%)
Infections and infestations
Abdominal infection	4/1008 (0.4%)
Abdominal sepsis	2/1008 (0.2%)
Anal abscess	1/1008 (0.1%)
Appendiceal abscess	1/1008 (0.1%)
Appendicitis	2/1008 (0.2%)
Arthritis bacterial	1/1008 (0.1%)
Bronchitis	2/1008 (0.2%)
Bronchopulmonary aspergillosis allergic	1/1008 (0.1%)
Cellulitis	6/1008 (0.6%)
Conjunctivitis	2/1008 (0.2%)
Cystitis	1/1008 (0.1%)
Device related infection	3/1008 (0.3%)
Device related sepsis	1/1008 (0.1%)
Diarrhoea infectious	1/1008 (0.1%)
Enterocolitis infectious	1/1008 (0.1%)
Erysipelas	7/1008 (0.7%)
Escherichia urinary tract infection	1/1008 (0.1%)
Gastroenteritis	4/1008 (0.4%)
Haematoma infection	1/1008 (0.1%)
Herpes zoster	1/1008 (0.1%)
Infected dermal cyst	1/1008 (0.1%)
Infected lymphocele	1/1008 (0.1%)
Infection	5/1008 (0.5%)
Infective exacerbation of chronic obstructive airways disease	1/1008 (0.1%)
Influenza	1/1008 (0.1%)
Latent tuberculosis	1/1008 (0.1%)
Lower respiratory tract infection	9/1008 (0.9%)
Lung infection	1/1008 (0.1%)
Perirectal abscess	1/1008 (0.1%)
Pneumococcal sepsis	1/1008 (0.1%)
Pneumonia	13/1008 (1.3%)
Pneumonia legionella	1/1008 (0.1%)
Pseudomembranous colitis	1/1008 (0.1%)
Pyelonephritis	1/1008 (0.1%)
Respiratory tract infection	5/1008 (0.5%)
Sepsis	8/1008 (0.8%)
Septic encephalopathy	1/1008 (0.1%)
Sinusitis	2/1008 (0.2%)
Soft tissue infection	1/1008 (0.1%)
Tonsillitis	1/1008 (0.1%)
Tooth abscess	2/1008 (0.2%)
Tooth infection	1/1008 (0.1%)
Tracheobronchitis	1/1008 (0.1%)
Urinary tract infection	11/1008 (1.1%)
Urosepsis	4/1008 (0.4%)
Vascular device infection	1/1008 (0.1%)
Viral diarrhoea	1/1008 (0.1%)
Viral infection	1/1008 (0.1%)
Wound infection	2/1008 (0.2%)
Gastroenteritis viral	1/1008 (0.1%)
Gastrointestinal infection	1/1008 (0.1%)
Meningitis	1/1008 (0.1%)
Septic shock	1/1008 (0.1%)
Tuberculosis	1/1008 (0.1%)
Upper respiratory tract infection	1/1008 (0.1%)
Injury, poisoning and procedural complications
Accidental overdose	1/1008 (0.1%)
Ankle fracture	1/1008 (0.1%)
Craniocerebral injury	1/1008 (0.1%)
Dose calculation error	1/1008 (0.1%)
Fall	4/1008 (0.4%)
Femoral neck fracture	1/1008 (0.1%)
Femur fracture	2/1008 (0.2%)
Fractured sacrum	1/1008 (0.1%)
Joint dislocation	1/1008 (0.1%)
Overdose	5/1008 (0.5%)
Procedural headache	1/1008 (0.1%)
Radiation necrosis	2/1008 (0.2%)
Radius fracture	1/1008 (0.1%)
Spinal compression fracture	1/1008 (0.1%)
Spinal fracture	1/1008 (0.1%)
Subdural haematoma	1/1008 (0.1%)
Ulna fracture	1/1008 (0.1%)
Hip fracture	1/1008 (0.1%)
Pubis fracture	1/1008 (0.1%)
Investigations
Alanine aminotransferase increased	3/1008 (0.3%)
Aspartate aminotransferase increased	2/1008 (0.2%)
Blood creatinine increased	1/1008 (0.1%)
CSF test abnormal	1/1008 (0.1%)
Gamma-glutamyltransferase increased	1/1008 (0.1%)
General physical condition abnormal	1/1008 (0.1%)
International normalised ratio increased	1/1008 (0.1%)
Lipase increased	2/1008 (0.2%)
Pancreatic enzymes increased	1/1008 (0.1%)
Transaminases increased	2/1008 (0.2%)
Troponin T increased	1/1008 (0.1%)
Metabolism and nutrition disorders
Cachexia	1/1008 (0.1%)
Dehydration	4/1008 (0.4%)
Diabetes mellitus	3/1008 (0.3%)
Hypercalcaemia	1/1008 (0.1%)
Hyperglycaemia	7/1008 (0.7%)
Hyperkalaemia	2/1008 (0.2%)
Hypernatraemia	1/1008 (0.1%)
Hypocalcaemia	2/1008 (0.2%)
Hypoglycaemia	5/1008 (0.5%)
Hyponatraemia	6/1008 (0.6%)
Hypoproteinaemia	1/1008 (0.1%)
Ketoacidosis	1/1008 (0.1%)
Type 1 diabetes mellitus	1/1008 (0.1%)
Decreased appetite	1/1008 (0.1%)
Metabolic acidosis	1/1008 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/1008 (0.1%)
Arthritis	1/1008 (0.1%)
Back pain	8/1008 (0.8%)
Bone pain	2/1008 (0.2%)
Fistula	1/1008 (0.1%)
Flank pain	1/1008 (0.1%)
Groin pain	1/1008 (0.1%)
Mobility decreased	2/1008 (0.2%)
Muscular weakness	1/1008 (0.1%)
Musculoskeletal chest pain	2/1008 (0.2%)
Myositis	1/1008 (0.1%)
Osteoarthritis	1/1008 (0.1%)
Osteochondrosis	1/1008 (0.1%)
Tendonitis	1/1008 (0.1%)
Pain in extremity	1/1008 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/1008 (0.1%)
Adenocarcinoma of colon	1/1008 (0.1%)
Anal neoplasm	1/1008 (0.1%)
Basal cell carcinoma	4/1008 (0.4%)
Bowen's disease	1/1008 (0.1%)
Breast cancer	1/1008 (0.1%)
Cancer pain	5/1008 (0.5%)
Chronic lymphocytic leukaemia	2/1008 (0.2%)
Infected neoplasm	1/1008 (0.1%)
Intracranial tumour haemorrhage	2/1008 (0.2%)
Malignant ascites	1/1008 (0.1%)
Malignant melanoma	3/1008 (0.3%)
Malignant neoplasm of spinal cord	1/1008 (0.1%)
Malignant neoplasm progression	278/1008 (27.6%)
Melanoma recurrent	1/1008 (0.1%)
Metastases to abdominal cavity	1/1008 (0.1%)
Metastases to adrenals	3/1008 (0.3%)
Metastases to bladder	1/1008 (0.1%)
Metastases to bone	2/1008 (0.2%)
Metastases to central nervous system	16/1008 (1.6%)
Metastases to liver	3/1008 (0.3%)
Metastases to lung	1/1008 (0.1%)
Metastases to meninges	1/1008 (0.1%)
Metastases to peritoneum	1/1008 (0.1%)
Metastases to skin	3/1008 (0.3%)
Metastases to spine	1/1008 (0.1%)
Metastasis	5/1008 (0.5%)
Metastatic malignant melanoma	15/1008 (1.5%)
Neoplasm	1/1008 (0.1%)
Pituitary tumour benign	1/1008 (0.1%)
Renal cell carcinoma	1/1008 (0.1%)
Squamous cell carcinoma	2/1008 (0.2%)
Squamous cell carcinoma of skin	1/1008 (0.1%)
Tonsil cancer	1/1008 (0.1%)
Tumour associated fever	2/1008 (0.2%)
Tumour flare	1/1008 (0.1%)
Tumour haemorrhage	8/1008 (0.8%)
Tumour necrosis	3/1008 (0.3%)
Non-Hodgkin's lymphoma	1/1008 (0.1%)
Tumour pain	1/1008 (0.1%)
Nervous system disorders
Altered state of consciousness	1/1008 (0.1%)
Aphasia	3/1008 (0.3%)
Brachial plexopathy	2/1008 (0.2%)
Brain injury	1/1008 (0.1%)
Brain oedema	3/1008 (0.3%)
Brain stem haemorrhage	1/1008 (0.1%)
Central nervous system lesion	1/1008 (0.1%)
Cerebral haematoma	1/1008 (0.1%)
Cerebral haemorrhage	1/1008 (0.1%)
Cerebrovascular accident	7/1008 (0.7%)
Encephalopathy	1/1008 (0.1%)
Epilepsy	3/1008 (0.3%)
Facial paralysis	2/1008 (0.2%)
Facial paresis	1/1008 (0.1%)
Haemorrhage intracranial	2/1008 (0.2%)
Headache	3/1008 (0.3%)
Hemiparesis	1/1008 (0.1%)
Hepatic encephalopathy	1/1008 (0.1%)
Hypertensive encephalopathy	1/1008 (0.1%)
Lumbar radiculopathy	1/1008 (0.1%)
Miller Fisher syndrome	1/1008 (0.1%)
Myasthenia gravis	1/1008 (0.1%)
Narcolepsy	1/1008 (0.1%)
Nervous system disorder	3/1008 (0.3%)
Peripheral nerve lesion	1/1008 (0.1%)
Peripheral sensorimotor neuropathy	1/1008 (0.1%)
Polyneuropathy	1/1008 (0.1%)
Seizure	6/1008 (0.6%)
Sensorimotor disorder	2/1008 (0.2%)
Spinal cord compression	4/1008 (0.4%)
Status epilepticus	1/1008 (0.1%)
Syncope	3/1008 (0.3%)
Diabetic hyperosmolar coma	1/1008 (0.1%)
Generalised tonic-clonic seizure	1/1008 (0.1%)
Lethargy	1/1008 (0.1%)
Neurological decompensation	1/1008 (0.1%)
Sciatica	1/1008 (0.1%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/1008 (0.1%)
Product Issues
Device dislocation	1/1008 (0.1%)
Psychiatric disorders
Confusional state	4/1008 (0.4%)
Depression	3/1008 (0.3%)
Personality change	1/1008 (0.1%)
Schizophrenia	1/1008 (0.1%)
Psychotic disorder	1/1008 (0.1%)
Renal and urinary disorders
Acute kidney injury	9/1008 (0.9%)
Autoimmune nephritis	1/1008 (0.1%)
Bladder pain	1/1008 (0.1%)
Hydronephrosis	2/1008 (0.2%)
Nephrolithiasis	1/1008 (0.1%)
Postrenal failure	1/1008 (0.1%)
Renal failure	4/1008 (0.4%)
Renal impairment	1/1008 (0.1%)
Tubulointerstitial nephritis	2/1008 (0.2%)
Ureteric stenosis	1/1008 (0.1%)
Urinary tract obstruction	2/1008 (0.2%)
Urinary retention	1/1008 (0.1%)
Reproductive system and breast disorders
Ovarian cyst ruptured	1/1008 (0.1%)
Pelvic pain	1/1008 (0.1%)
Penile oedema	1/1008 (0.1%)
Testicular oedema	1/1008 (0.1%)
Vaginal haemorrhage	1/1008 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/1008 (0.2%)
Aspiration	1/1008 (0.1%)
Atelectasis	3/1008 (0.3%)
Cough	1/1008 (0.1%)
Dyspnoea	8/1008 (0.8%)
Haemoptysis	1/1008 (0.1%)
Interstitial lung disease	2/1008 (0.2%)
Pleural effusion	9/1008 (0.9%)
Pneumonia aspiration	2/1008 (0.2%)
Pneumonitis	10/1008 (1%)
Pneumothorax	1/1008 (0.1%)
Pulmonary embolism	14/1008 (1.4%)
Pulmonary toxicity	1/1008 (0.1%)
Respiratory failure	2/1008 (0.2%)
Respiratory muscle weakness	1/1008 (0.1%)
Skin and subcutaneous tissue disorders
Dermatitis	1/1008 (0.1%)
Dermatitis exfoliative	1/1008 (0.1%)
Drug eruption	1/1008 (0.1%)
Erythema	1/1008 (0.1%)
Generalised erythema	1/1008 (0.1%)
Pemphigoid	2/1008 (0.2%)
Pruritus generalised	1/1008 (0.1%)
Rash generalised	1/1008 (0.1%)
Rash maculo-papular	2/1008 (0.2%)
Skin ulcer	3/1008 (0.3%)
Erythema multiforme	1/1008 (0.1%)
Rash macular	1/1008 (0.1%)
Vascular disorders
Angiopathy	1/1008 (0.1%)
Circulatory collapse	1/1008 (0.1%)
Deep vein thrombosis	1/1008 (0.1%)
Embolism	1/1008 (0.1%)
Extremity necrosis	1/1008 (0.1%)
Hypertension	2/1008 (0.2%)
Hypertensive crisis	3/1008 (0.3%)
Hypotension	4/1008 (0.4%)
Jugular vein thrombosis	1/1008 (0.1%)
Lymphoedema	3/1008 (0.3%)
Peripheral venous disease	1/1008 (0.1%)
Superior vena cava syndrome	1/1008 (0.1%)
Thrombosis	1/1008 (0.1%)
Vascular occlusion	1/1008 (0.1%)
Lymphocele	1/1008 (0.1%)
Other (Not Including Serious) Adverse Events
	NIVOLUMAB 3 MG/KG IV
	Affected / at Risk (%)	# Events
Total	857/1008 (85%)
Blood and lymphatic system disorders
Anaemia	126/1008 (12.5%)
Endocrine disorders
Hypothyroidism	114/1008 (11.3%)
Gastrointestinal disorders
Abdominal pain	102/1008 (10.1%)
Abdominal pain upper	58/1008 (5.8%)
Constipation	132/1008 (13.1%)
Diarrhoea	210/1008 (20.8%)
Nausea	212/1008 (21%)
Vomiting	120/1008 (11.9%)
Dry mouth	51/1008 (5.1%)
General disorders
Asthenia	168/1008 (16.7%)
Fatigue	295/1008 (29.3%)
Oedema peripheral	81/1008 (8%)
Pyrexia	130/1008 (12.9%)
Infections and infestations
Nasopharyngitis	88/1008 (8.7%)
Urinary tract infection	54/1008 (5.4%)
Investigations
Alanine aminotransferase increased	83/1008 (8.2%)
Aspartate aminotransferase increased	78/1008 (7.7%)
Blood alkaline phosphatase increased	52/1008 (5.2%)
Lipase increased	79/1008 (7.8%)
Weight decreased	63/1008 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	143/1008 (14.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	148/1008 (14.7%)
Back pain	116/1008 (11.5%)
Musculoskeletal pain	55/1008 (5.5%)
Myalgia	62/1008 (6.2%)
Pain in extremity	93/1008 (9.2%)
Nervous system disorders
Headache	122/1008 (12.1%)
Psychiatric disorders
Insomnia	55/1008 (5.5%)
Respiratory, thoracic and mediastinal disorders
Cough	134/1008 (13.3%)
Dyspnoea	81/1008 (8%)
Skin and subcutaneous tissue disorders
Dry skin	54/1008 (5.4%)
Pruritus	115/1008 (11.4%)
Pruritus generalised	89/1008 (8.8%)
Rash	54/1008 (5.4%)
Vitiligo	77/1008 (7.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.