Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma (CheckMate 238)

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ClinicalTrials.gov Identifier: NCT02388906

Recruitment Status : Active, not recruiting

First Posted : March 17, 2015

Results First Posted : June 15, 2021

Last Update Posted : January 10, 2024

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Sponsor:

Collaborator:

Ono Pharmaceutical Co. Ltd

Information provided by (Responsible Party):

Bristol-Myers Squibb

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Melanoma
Interventions	Drug: Ipilimumab Drug: Nivolumab Other: Placebo matching Ipilimumab Other: Placebo matching Nivolumab
Enrollment	906

Participant Flow

Recruitment Details
Pre-assignment Details	906 participants randomized and 905 treated. Reason for not treated: 1 participant withdrew consent.


Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Period Title: Pre-Treatment Period
Started ^[1]	453	453
Completed ^[2]	452	453
Not Completed	1	0
Reason Not Completed
Participant withdrew consent	1	0
[1] Started=Randomized [2] completed=treated
Period Title: Treatment Period
Started ^[1]	452	453
Completed ^[2]	275	122
Not Completed	177	331
Reason Not Completed
Disease progression	121	101
Study drug toxicity	41	208
Adverse Event (AE) unrelated to study drug	5	5
Participant request to stop treatment	5	9
Participant withdrew consent	2	3
Poor/non-compliance	0	1
Participant no longer meets study criteria	0	1
Other reasons	3	3
[1] Started=Treated [2] Completed=Finished the treatment period

Baseline Characteristics

Arm/Group Title		Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg	Total
Arm/Group Description		Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...	Total of all reporting groups
Arm/Group Description		Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks	Total of all reporting groups
Overall Number of Baseline Participants		453	453	906
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All Randomized Participants
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	453 participants	453 participants	906 participants
		54.4 (13.34)	53.6 (13.50)	54.0 (13.42)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	453 participants	453 participants	906 participants
	Female	195 43.0%	184 40.6%	379 41.8%
	Male	258 57.0%	269 59.4%	527 58.2%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	453 participants	453 participants	906 participants
	Hispanic or Latino	6 1.3%	8 1.8%	14 1.5%
	Not Hispanic or Latino	215 47.5%	208 45.9%	423 46.7%
	Unknown or Not Reported	232 51.2%	237 52.3%	469 51.8%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	453 participants	453 participants	906 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	25 5.5%	18 4.0%	43 4.7%
	Native Hawaiian or Other Pacific Islander	1 0.2%	0 0.0%	1 0.1%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	425 93.8%	434 95.8%	859 94.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 0.4%	1 0.2%	3 0.3%

Outcome Measures

1.Primary Outcome


Title	Recurrence-free Survival (RFS)
Description	RFS is defined as the time between the date of randomization and the d...
Description	RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed	453	453
Median (95% Confidence Interval) Unit of Measure: Months
	52.37 ^[1] (42.51 to NA)	24.08 (16.56 to 35.09)

[1]

Upper limit not calculable as upper CI bound does not cross 50% threshold

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3 mg/kg, Ipilimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log rank

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.60 to 0.86
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival (OS)
Description	OS is defined as as the time between the date of randomization and the...
Description	OS is defined as as the time between the date of randomization and the date of death.
Time Frame	up to 60 months

Outcome Measure Data

Analysis Population Description

All randomized Participants


Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed	453	453
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

Median not reached due to insufficient death events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 3 mg/kg, Ipilimumab 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3148
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95.03% 0.66 to 1.14
	Estimation Comments	Stratified Cox proportional hazard model

3.Secondary Outcome


Title	The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
Description	the safety and tolerability of Nivolumab and Ipilimumab was measured b...
Description	the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events
Time Frame	reported between first dose and 30 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All treated participants


Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed	452	453
Measure Type: Number Unit of Measure: Participants
Grade 3-4	116	251
Any grade	440	446

4.Secondary Outcome


Title	The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events
Description	The Safety and Tolerability of nivolumab and ipilimumab was measured b...
Description	The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events
Time Frame	reported between the first dose and 30 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

all treated participants


Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed	452	453
Measure Type: Number Unit of Measure: Participants
Grade 3-4	48	145
Any grade	80	184

5.Secondary Outcome


Title	the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths
Description	the safety and tolerability of Nivolumab and Ipilimumab wasmeasured by...
Description	the safety and tolerability of Nivolumab and Ipilimumab wasmeasured by the incidence of Deaths
Time Frame	reported between first dose and 30 to 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All treated participants


Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed	452	453
Measure Type: Number Unit of Measure: Participants
	100	111

6.Secondary Outcome


Title	The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities
Description	The Safety and Tolerability of Nivolumab and Ipilimumab measured by th...
Description	The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities.
Time Frame	reported after first dose and within 30 days of last dose of the study therapy

Outcome Measure Data

Analysis Population Description

Participants with a CTC graded Laboratory Result for the given parameter from both Baseline and On-treatment


Arm/Group Title		Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:		Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed		452	453
Measure Type: Number Unit of Measure: Participants
Heamoglobin (grade1-4)	Number Analyzed	447 participants	440 participants
Heamoglobin (grade1-4)		114	148
Heamoglobin (Grade 3-4)	Number Analyzed	447 participants	440 participants
Heamoglobin (Grade 3-4)		0	2
Platelet count (grade1-4)	Number Analyzed	447 participants	440 participants
Platelet count (grade1-4)		27	25
Platelet count ( grade 3-4)	Number Analyzed	447 participants	440 participants
Platelet count ( grade 3-4)		0	1
Leukocytes (grade1-4)	Number Analyzed	447 participants	440 participants
Leukocytes (grade1-4)		62	12
Leukocytes (grade 3-4)	Number Analyzed	447 participants	440 participants
Leukocytes (grade 3-4)		0	1
Lymphocytes (grade1-4)	Number Analyzed	446 participants	439 participants
Lymphocytes (grade1-4)		118	54
Lymphocytes (grade 3-4)	Number Analyzed	446 participants	439 participants
Lymphocytes (grade 3-4)		2	4
Absolute Neutrophil count (Grade1-4)	Number Analyzed	447 participants	439 participants
Absolute Neutrophil count (Grade1-4)		56	26
Absolute Neutrophil count (Grade3-4)	Number Analyzed	447 participants	439 participants
Absolute Neutrophil count (Grade3-4)		0	2
Alkaline Phosphatase (grade1-4)	Number Analyzed	441 participants	437 participants
Alkaline Phosphatase (grade1-4)		35	69
Alkaline Phosphatase (Grade3-4)	Number Analyzed	441 participants	437 participants
Alkaline Phosphatase (Grade3-4)		1	3
Aspartate Aminotransferase (grade 1-4)	Number Analyzed	445 participants	440 participants
Aspartate Aminotransferase (grade 1-4)		105	144
Aspartate Aminotransferase(grade 3-4)	Number Analyzed	445 participants	440 participants
Aspartate Aminotransferase(grade 3-4)		6	39
Alkaline Aminotransferase (grade 1-4)	Number Analyzed	447 participants	443 participants
Alkaline Aminotransferase (grade 1-4)		113	176
Alkaline Aminotransferase(grade 3-4)	Number Analyzed	447 participants	443 participants
Alkaline Aminotransferase(grade 3-4)		8	52
Total Bilirubin (grade 1-4)	Number Analyzed	446 participants	439 participants
Total Bilirubin (grade 1-4)		33	43
Total Bilirubin (grade 3-4)	Number Analyzed	446 participants	439 participants
Total Bilirubin (grade 3-4)		0	5
Creatinine ( grade1-4)	Number Analyzed	446 participants	440 participants
Creatinine ( grade1-4)		55	56
Creatinine (grade 3-4)	Number Analyzed	446 participants	440 participants
Creatinine (grade 3-4)		0	0
Total Amylase ( grade1-4)	Number Analyzed	400 participants	392 participants
Total Amylase ( grade1-4)		68	52
Total Amylase (grade 3-4)	Number Analyzed	400 participants	392 participants
Total Amylase (grade 3-4)		13	12
Total Lipase ( grade1-4)	Number Analyzed	438 participants	427 participants
Total Lipase ( grade1-4)		109	100
Total Lipase (grade 3-4)	Number Analyzed	438 participants	427 participants
Total Lipase (grade 3-4)		31	38
Hypernatremia ( grade1-4)	Number Analyzed	446 participants	438 participants
Hypernatremia ( grade1-4)		35	20
Hypernatremia (grade 3-4)	Number Analyzed	446 participants	438 participants
Hypernatremia (grade 3-4)		0	0
Hyponatremia ( grade1-4)	Number Analyzed	446 participants	438 participants
Hyponatremia ( grade1-4)		72	96
Hyponatremia (grade 3-4)	Number Analyzed	446 participants	438 participants
Hyponatremia (grade 3-4)		5	14
Hyperkalemia ( grade1-4)	Number Analyzed	445 participants	439 participants
Hyperkalemia ( grade1-4)		55	39
Hyperkalemia (grade 3-4)	Number Analyzed	445 participants	439 participants
Hyperkalemia (grade 3-4)		1	2
Hypokalemia ( grade1-4)	Number Analyzed	445 participants	439 participants
Hypokalemia ( grade1-4)		37	45
Hypokalemia(grade 3-4)	Number Analyzed	445 participants	439 participants
Hypokalemia(grade 3-4)		5	9
Hypercalcemia ( grade1-4)	Number Analyzed	434 participants	422 participants
Hypercalcemia ( grade1-4)		14	18
Hypercalcemia(grade 3-4)	Number Analyzed	434 participants	422 participants
Hypercalcemia(grade 3-4)		0	0
Hypocalcemia ( grade1-4)	Number Analyzed	434 participants	422 participants
Hypocalcemia ( grade1-4)		46	73
Hypocalcemia(grade 3-4)	Number Analyzed	434 participants	422 participants
Hypocalcemia(grade 3-4)		3	2
Hypermagnesemia ( grade1-4)	Number Analyzed	441 participants	435 participants
Hypermagnesemia ( grade1-4)		20	7
Hypermagnesemia(grade 3-4)	Number Analyzed	441 participants	435 participants
Hypermagnesemia(grade 3-4)		2	1
Hypomagnesemia ( grade1-4)	Number Analyzed	441 participants	435 participants
Hypomagnesemia ( grade1-4)		39	32
Hypomagnesemia(grade 3-4)	Number Analyzed	441 participants	435 participants
Hypomagnesemia(grade 3-4)		1	0

7.Secondary Outcome


Title	Recurrence-free Survival by PD-L1 Expression
Description	Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane ex...
Description	Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression)
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

All randomized Participants


Arm/Group Title		Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:		Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed		453	453
Median (95% Confidence Interval) Unit of Measure: Months
Participants with >= 5% PD-L1 Expression,	Number Analyzed	153 participants	154 participants
Participants with >= 5% PD-L1 Expression,		NA ^[1] (50.17 to NA)	52.86 ^[2] (24.15 to NA)
Participants with < 5% PD-L1 Expression,	Number Analyzed	275 participants	286 participants
Participants with < 5% PD-L1 Expression,		36.30 ^[2] (19.84 to NA)	16.56 (10.87 to 25.79)
Participants with Non-quantifiable PD-L1 Expression	Number Analyzed	25 participants	13 participants
Participants with Non-quantifiable PD-L1 Expression		NA ^[1] (6.70 to NA)	28.25 ^[2] (4.76 to NA)

[1]

Median not reached as insufficient progression events among responders

[2]

Upper limit not calculable as upper CI bound does not cross 50% threshold

8.Secondary Outcome


Title	Health Related Quality of Life (HRQoL) Evaluation
Description	HRQoL was measured by mean changes from baseline in EORTC-QLQ-C30 glob...
Description	HRQoL was measured by mean changes from baseline in EORTC-QLQ-C30 global health status/QoL composite scale and in remaining EORTC QLQ-C30 scales in all randomized participants. EORTC QLQ-C30 is the most commonly used QoL instrument in melanoma clinical studies, is a 30-item instrument that has gained wide acceptance in oncology clinical studies and comprises 5 functional scales (physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Except for the overall health status and global quality of life items, responses for all items are 4 point categorical scales ranging from 1 (Not at all) to 4 (Very much). The overall health status/quality of life responses are 7-point Likert scales for which higher score reflects higher health status/quality of life for the 7-point Likert scale.
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

All randomized Participants with values from the second follow-up visit


Arm/Group Title		Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description:		Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description:		Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
Overall Number of Participants Analyzed		334	308
Mean (Standard Deviation) Unit of Measure: Scores on a scale
Physical functioning	Number Analyzed	327 participants	307 participants
Physical functioning		-2.04 (15.134)	-4.88 (15.713)
Role functioning	Number Analyzed	329 participants	307 participants
Role functioning		-2.43 (25.219)	-3.85 (29.951)
Emotional functioning	Number Analyzed	330 participants	307 participants
Emotional functioning		0.18 (20.282)	1.43 (17.911)
Cognitive functioning	Number Analyzed	330 participants	307 participants
Cognitive functioning		-3.74 (18.364)	-4.67 (16.664)
Social functioning	Number Analyzed	330 participants	307 participants
Social functioning		-0.51 (22.085)	-3.53 (26.391)
Global health status	Number Analyzed	330 participants	307 participants
Global health status		-5.81 (20.046)	-7.00 (23.109)
Fatigue	Number Analyzed	329 participants	307 participants
Fatigue		6.45 (21.605)	9.05 (23.475)
Nausea and vomiting	Number Analyzed	329 participants	307 participants
Nausea and vomiting		2.23 (12.622)	1.90 (11.473)
Pain	Number Analyzed	331 participants	308 participants
Pain		1.66 (23.314)	4.38 (23.641)
Dyspnea	Number Analyzed	328 participants	306 participants
Dyspnea		7.32 (22.741)	5.45 (20.364)
Insomnia	Number Analyzed	329 participants	306 participants
Insomnia		1.82 (28.692)	3.05 (28.785)
Appetite loss	Number Analyzed	328 participants	307 participants
Appetite loss		4.07 (22.660)	2.61 (19.257)
Constipation	Number Analyzed	329 participants	307 participants
Constipation		1.11 (17.904)	0.33 (18.373)
Diarrhea	Number Analyzed	330 participants	306 participants
Diarrhea		1.31 (20.831)	3.38 (21.242)
Financial difficulties	Number Analyzed	330 participants	306 participants
Financial difficulties		-1.41 (23.348)	0.54 (20.282)

Adverse Events

Time Frame	Within 30 days of the last dose of study drug and continue until 100 days from the last dose of the study drug (up to 48 months).
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
Arm/Group Description	Nivolumab 3 mg/kg IV q2 wks and Ipi...	Ipilimumab 10 mg/kg IV q3 wks for 4...
Arm/Group Description	Nivolumab 3 mg/kg IV q2 wks and Ipilimumab placebo IV q3 wks for 4 doses then q12 wks starting at Wk 24	Ipilimumab 10 mg/kg IV q3 wks for 4 doses then q12 wks starting at Wk 24 and Nivolumab placebo IV q2 wks
All-Cause Mortality
	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	100/452 (22.12%)	111/453 (24.50%)
Serious Adverse Events Serious Adverse Events
	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	106/452 (23.45%)	215/453 (47.46%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Disseminated intravascular coagulation ^† 1	2/452 (0.44%)	0/453 (0.00%)
Lymph node pain ^† 1	1/452 (0.22%)	0/453 (0.00%)
Lymphadenopathy ^† 1	0/452 (0.00%)	2/453 (0.44%)
Lymphadenopathy mediastinal ^† 1	1/452 (0.22%)	0/453 (0.00%)
Neutropenia ^† 1	1/452 (0.22%)	1/453 (0.22%)
Thrombotic thrombocytopenic purpura ^† 1	0/452 (0.00%)	1/453 (0.22%)
Cardiac disorders
Angina pectoris ^† 1	1/452 (0.22%)	0/453 (0.00%)
Atrial fibrillation ^† 1	1/452 (0.22%)	2/453 (0.44%)
Bradycardia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Left ventricular dysfunction ^† 1	0/452 (0.00%)	1/453 (0.22%)
Myocardial ischaemia ^† 1	1/452 (0.22%)	0/453 (0.00%)
Ear and labyrinth disorders
Deafness ^† 1	0/452 (0.00%)	1/453 (0.22%)
Endocrine disorders
Adrenal insufficiency ^† 1	0/452 (0.00%)	5/453 (1.10%)
Adrenal suppression ^† 1	0/452 (0.00%)	1/453 (0.22%)
Adrenocortical insufficiency acute ^† 1	1/452 (0.22%)	0/453 (0.00%)
Glucocorticoid deficiency ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hyperthyroidism ^† 1	2/452 (0.44%)	1/453 (0.22%)
Hypophysitis ^† 1	3/452 (0.66%)	18/453 (3.97%)
Hypopituitarism ^† 1	0/452 (0.00%)	1/453 (0.22%)
Hypothalamo-pituitary disorder ^† 1	0/452 (0.00%)	1/453 (0.22%)
Hypothyroidism ^† 1	1/452 (0.22%)	1/453 (0.22%)
Lymphocytic hypophysitis ^† 1	0/452 (0.00%)	5/453 (1.10%)
Eye disorders
Uveitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Vision blurred ^† 1	0/452 (0.00%)	1/453 (0.22%)
Gastrointestinal disorders
Abdominal pain ^† 1	0/452 (0.00%)	3/453 (0.66%)
Abdominal pain upper ^† 1	1/452 (0.22%)	1/453 (0.22%)
Autoimmune colitis ^† 1	0/452 (0.00%)	5/453 (1.10%)
Colitis ^† 1	5/452 (1.11%)	41/453 (9.05%)
Diarrhoea ^† 1	5/452 (1.11%)	37/453 (8.17%)
Duodenitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Enteritis ^† 1	0/452 (0.00%)	2/453 (0.44%)
Enterocolitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Gastric ulcer ^† 1	0/452 (0.00%)	1/453 (0.22%)
Gastritis ^† 1	0/452 (0.00%)	3/453 (0.66%)
Gastrointestinal perforation ^† 1	0/452 (0.00%)	1/453 (0.22%)
Glossitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Ileus ^† 1	0/452 (0.00%)	1/453 (0.22%)
Immune-mediated enterocolitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Inguinal hernia ^† 1	1/452 (0.22%)	0/453 (0.00%)
Intestinal perforation ^† 1	0/452 (0.00%)	2/453 (0.44%)
Intussusception ^† 1	1/452 (0.22%)	0/453 (0.00%)
Large intestinal haemorrhage ^† 1	0/452 (0.00%)	1/453 (0.22%)
Large intestine perforation ^† 1	0/452 (0.00%)	1/453 (0.22%)
Nausea ^† 1	1/452 (0.22%)	3/453 (0.66%)
Pancreatitis ^† 1	1/452 (0.22%)	2/453 (0.44%)
Proctitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Small intestinal obstruction ^† 1	0/452 (0.00%)	1/453 (0.22%)
Stomatitis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Subileus ^† 1	0/452 (0.00%)	1/453 (0.22%)
Vomiting ^† 1	2/452 (0.44%)	2/453 (0.44%)
General disorders
Asthenia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Facial pain ^† 1	0/452 (0.00%)	1/453 (0.22%)
Hyperthermia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Influenza like illness ^† 1	0/452 (0.00%)	2/453 (0.44%)
Malaise ^† 1	0/452 (0.00%)	1/453 (0.22%)
Mucosal inflammation ^† 1	1/452 (0.22%)	0/453 (0.00%)
Non-cardiac chest pain ^† 1	1/452 (0.22%)	1/453 (0.22%)
Pyrexia ^† 1	8/452 (1.77%)	11/453 (2.43%)
Hepatobiliary disorders
Autoimmune hepatitis ^† 1	1/452 (0.22%)	1/453 (0.22%)
Cholecystitis acute ^† 1	0/452 (0.00%)	1/453 (0.22%)
Cholestasis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Drug-induced liver injury ^† 1	1/452 (0.22%)	2/453 (0.44%)
Hepatic function abnormal ^† 1	1/452 (0.22%)	2/453 (0.44%)
Hepatic haemorrhage ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hepatitis ^† 1	0/452 (0.00%)	8/453 (1.77%)
Hepatitis acute ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hepatobiliary disease ^† 1	0/452 (0.00%)	1/453 (0.22%)
Hepatocellular injury ^† 1	1/452 (0.22%)	1/453 (0.22%)
Hepatotoxicity ^† 1	0/452 (0.00%)	2/453 (0.44%)
Hypertransaminasaemia ^† 1	1/452 (0.22%)	1/453 (0.22%)
Immune-mediated hepatitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Immune system disorders
Cytokine release syndrome ^† 1	0/452 (0.00%)	1/453 (0.22%)
Sarcoidosis ^† 1	2/452 (0.44%)	0/453 (0.00%)
Infections and infestations
Anorectal infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Appendicitis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Bacteraemia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Brain abscess ^† 1	1/452 (0.22%)	0/453 (0.00%)
Bronchitis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Cellulitis ^† 1	7/452 (1.55%)	3/453 (0.66%)
Clostridium difficile colitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Device related infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Encephalitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Erysipelas ^† 1	1/452 (0.22%)	3/453 (0.66%)
Fungal sepsis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Gastroenteritis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Infected seroma ^† 1	1/452 (0.22%)	0/453 (0.00%)
Infection ^† 1	1/452 (0.22%)	1/453 (0.22%)
Infectious mononucleosis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Lower respiratory tract infection ^† 1	1/452 (0.22%)	0/453 (0.00%)
Meningitis ^† 1	0/452 (0.00%)	2/453 (0.44%)
Meningitis aseptic ^† 1	1/452 (0.22%)	0/453 (0.00%)
Mucormycosis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Myelitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Pharyngitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Pharyngotonsillitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Pneumonia ^† 1	4/452 (0.88%)	6/453 (1.32%)
Pulmonary mycosis ^† 1	1/452 (0.22%)	1/453 (0.22%)
Pulmonary sepsis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Rash pustular ^† 1	1/452 (0.22%)	0/453 (0.00%)
Respiratory tract infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Sepsis ^† 1	1/452 (0.22%)	3/453 (0.66%)
Sinobronchitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Sinusitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Skin infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Soft tissue infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Staphylococcal bacteraemia ^† 1	1/452 (0.22%)	0/453 (0.00%)
Staphylococcal infection ^† 1	1/452 (0.22%)	0/453 (0.00%)
Tonsillitis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Upper respiratory tract infection ^† 1	0/452 (0.00%)	2/453 (0.44%)
Urinary tract infection ^† 1	0/452 (0.00%)	3/453 (0.66%)
Urosepsis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Viral infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Wound infection ^† 1	0/452 (0.00%)	1/453 (0.22%)
Injury, poisoning and procedural complications
Craniocerebral injury ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hand fracture ^† 1	1/452 (0.22%)	0/453 (0.00%)
Incisional hernia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Post procedural haematoma ^† 1	0/452 (0.00%)	1/453 (0.22%)
Vascular pseudoaneurysm ^† 1	1/452 (0.22%)	0/453 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	2/452 (0.44%)	5/453 (1.10%)
Aspartate aminotransferase increased ^† 1	1/452 (0.22%)	0/453 (0.00%)
Blood bilirubin increased ^† 1	1/452 (0.22%)	0/453 (0.00%)
Blood creatine phosphokinase increased ^† 1	1/452 (0.22%)	0/453 (0.00%)
Body temperature increased ^† 1	1/452 (0.22%)	0/453 (0.00%)
Electrocardiogram abnormal ^† 1	0/452 (0.00%)	1/453 (0.22%)
Faecal volume increased ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hepatic enzyme increased ^† 1	0/452 (0.00%)	2/453 (0.44%)
Liver function test increased ^† 1	0/452 (0.00%)	3/453 (0.66%)
Neutrophil count decreased ^† 1	0/452 (0.00%)	1/453 (0.22%)
Staphylococcus test positive ^† 1	1/452 (0.22%)	0/453 (0.00%)
Transaminases increased ^† 1	0/452 (0.00%)	7/453 (1.55%)
Metabolism and nutrition disorders
Dehydration ^† 1	0/452 (0.00%)	4/453 (0.88%)
Diabetes mellitus inadequate control ^† 1	1/452 (0.22%)	0/453 (0.00%)
Fulminant type 1 diabetes mellitus ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hyperglycaemia ^† 1	1/452 (0.22%)	2/453 (0.44%)
Hyperkalaemia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Hypocalcaemia ^† 1	0/452 (0.00%)	2/453 (0.44%)
Hypokalaemia ^† 1	0/452 (0.00%)	2/453 (0.44%)
Hyponatraemia ^† 1	1/452 (0.22%)	2/453 (0.44%)
Type 1 diabetes mellitus ^† 1	1/452 (0.22%)	0/453 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Arthritis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Back pain ^† 1	0/452 (0.00%)	2/453 (0.44%)
Musculoskeletal chest pain ^† 1	0/452 (0.00%)	2/453 (0.44%)
Musculoskeletal pain ^† 1	0/452 (0.00%)	1/453 (0.22%)
Myalgia ^† 1	1/452 (0.22%)	1/453 (0.22%)
Neck pain ^† 1	1/452 (0.22%)	1/453 (0.22%)
Rheumatoid arthritis ^† 1	2/452 (0.44%)	0/453 (0.00%)
Temporomandibular joint syndrome ^† 1	1/452 (0.22%)	0/453 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon ^† 1	0/452 (0.00%)	1/453 (0.22%)
Basal cell carcinoma ^† 1	3/452 (0.66%)	3/453 (0.66%)
Bowen's disease ^† 1	1/452 (0.22%)	0/453 (0.00%)
Breast cancer ^† 1	1/452 (0.22%)	0/453 (0.00%)
Cancer pain ^† 1	1/452 (0.22%)	0/453 (0.00%)
Chronic lymphocytic leukaemia ^† 1	1/452 (0.22%)	0/453 (0.00%)
Malignant melanoma ^† 1	2/452 (0.44%)	0/453 (0.00%)
Malignant neoplasm progression ^† 1	4/452 (0.88%)	3/453 (0.66%)
Melanoma recurrent ^† 1	10/452 (2.21%)	2/453 (0.44%)
Metastatic malignant melanoma ^† 1	2/452 (0.44%)	1/453 (0.22%)
Neoplasm malignant ^† 1	3/452 (0.66%)	0/453 (0.00%)
Neoplasm recurrence ^† 1	1/452 (0.22%)	2/453 (0.44%)
Papillary thyroid cancer ^† 1	0/452 (0.00%)	2/453 (0.44%)
Renal cell carcinoma ^† 1	1/452 (0.22%)	0/453 (0.00%)
Squamous cell carcinoma ^† 1	5/452 (1.11%)	1/453 (0.22%)
Squamous cell carcinoma of the tongue ^† 1	0/452 (0.00%)	1/453 (0.22%)
Tumour pain ^† 1	1/452 (0.22%)	0/453 (0.00%)
Nervous system disorders
Cerebrovascular accident ^† 1	1/452 (0.22%)	0/453 (0.00%)
Dysarthria ^† 1	1/452 (0.22%)	0/453 (0.00%)
Encephalopathy ^† 1	0/452 (0.00%)	1/453 (0.22%)
Facial nerve disorder ^† 1	0/452 (0.00%)	1/453 (0.22%)
Facial paralysis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Haemorrhage intracranial ^† 1	1/452 (0.22%)	0/453 (0.00%)
Headache ^† 1	0/452 (0.00%)	4/453 (0.88%)
Hypotonia ^† 1	0/452 (0.00%)	1/453 (0.22%)
IVth nerve disorder ^† 1	0/452 (0.00%)	1/453 (0.22%)
Loss of consciousness ^† 1	1/452 (0.22%)	0/453 (0.00%)
Miller Fisher syndrome ^† 1	0/452 (0.00%)	1/453 (0.22%)
Neuropathy peripheral ^† 1	0/452 (0.00%)	1/453 (0.22%)
Neurosarcoidosis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Peripheral sensory neuropathy ^† 1	0/452 (0.00%)	1/453 (0.22%)
Polyneuropathy ^† 1	0/452 (0.00%)	1/453 (0.22%)
Syncope ^† 1	2/452 (0.44%)	3/453 (0.66%)
Transient ischaemic attack ^† 1	1/452 (0.22%)	0/453 (0.00%)
Psychiatric disorders
Dependence ^† 1	1/452 (0.22%)	0/453 (0.00%)
Renal and urinary disorders
Acute kidney injury ^† 1	3/452 (0.66%)	1/453 (0.22%)
Cystitis haemorrhagic ^† 1	0/452 (0.00%)	1/453 (0.22%)
Nephrolithiasis ^† 1	1/452 (0.22%)	0/453 (0.00%)
Renal colic ^† 1	1/452 (0.22%)	1/453 (0.22%)
Tubulointerstitial nephritis ^† 1	1/452 (0.22%)	1/453 (0.22%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	1/452 (0.22%)	0/453 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	1/452 (0.22%)	1/453 (0.22%)
Dyspnoea ^† 1	2/452 (0.44%)	1/453 (0.22%)
Hypoxia ^† 1	0/452 (0.00%)	1/453 (0.22%)
Immune-mediated pneumonitis ^† 1	1/452 (0.22%)	1/453 (0.22%)
Interstitial lung disease ^† 1	2/452 (0.44%)	0/453 (0.00%)
Lung disorder ^† 1	1/452 (0.22%)	0/453 (0.00%)
Lung infiltration ^† 1	0/452 (0.00%)	1/453 (0.22%)
Obstructive airways disorder ^† 1	0/452 (0.00%)	1/453 (0.22%)
Pneumonitis ^† 1	2/452 (0.44%)	5/453 (1.10%)
Pneumothorax ^† 1	1/452 (0.22%)	0/453 (0.00%)
Pulmonary embolism ^† 1	1/452 (0.22%)	4/453 (0.88%)
Skin and subcutaneous tissue disorders
Acne ^† 1	1/452 (0.22%)	0/453 (0.00%)
Dermatitis exfoliative generalised ^† 1	0/452 (0.00%)	1/453 (0.22%)
Drug reaction with eosinophilia and systemic symptoms ^† 1	1/452 (0.22%)	0/453 (0.00%)
Eczema ^† 1	0/452 (0.00%)	1/453 (0.22%)
Rash ^† 1	1/452 (0.22%)	4/453 (0.88%)
Rash maculo-papular ^† 1	2/452 (0.44%)	1/453 (0.22%)
Skin toxicity ^† 1	1/452 (0.22%)	0/453 (0.00%)
Toxic skin eruption ^† 1	0/452 (0.00%)	1/453 (0.22%)
Urticaria ^† 1	0/452 (0.00%)	1/453 (0.22%)
Vascular disorders
Capillary leak syndrome ^† 1	0/452 (0.00%)	2/453 (0.44%)
Hypertension ^† 1	1/452 (0.22%)	0/453 (0.00%)
Hypotension ^† 1	2/452 (0.44%)	2/453 (0.44%)
Orthostatic hypotension ^† 1	0/452 (0.00%)	1/453 (0.22%)
Temporal arteritis ^† 1	0/452 (0.00%)	1/453 (0.22%)
Venous thrombosis limb ^† 1	0/452 (0.00%)	1/453 (0.22%)
1 Term from vocabulary, 22.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab 3 mg/kg	Ipilimumab 10 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	421/452 (93.14%)	438/453 (96.69%)
Blood and lymphatic system disorders
Anaemia ^† 1	13/452 (2.88%)	26/453 (5.74%)
Endocrine disorders
Hyperthyroidism ^† 1	37/452 (8.19%)	22/453 (4.86%)
Hypophysitis ^† 1	6/452 (1.33%)	42/453 (9.27%)
Hypothyroidism ^† 1	53/452 (11.73%)	36/453 (7.95%)
Gastrointestinal disorders
Abdominal pain ^† 1	54/452 (11.95%)	78/453 (17.22%)
Abdominal pain upper ^† 1	33/452 (7.30%)	21/453 (4.64%)
Colitis ^† 1	10/452 (2.21%)	30/453 (6.62%)
Constipation ^† 1	47/452 (10.40%)	46/453 (10.15%)
Diarrhoea ^† 1	171/452 (37.83%)	250/453 (55.19%)
Dry mouth ^† 1	33/452 (7.30%)	23/453 (5.08%)
Dyspepsia ^† 1	21/452 (4.65%)	27/453 (5.96%)
Nausea ^† 1	110/452 (24.34%)	135/453 (29.80%)
Vomiting ^† 1	39/452 (8.63%)	68/453 (15.01%)
General disorders
Asthenia ^† 1	74/452 (16.37%)	72/453 (15.89%)
Chills ^† 1	11/452 (2.43%)	31/453 (6.84%)
Fatigue ^† 1	193/452 (42.70%)	197/453 (43.49%)
Influenza like illness ^† 1	32/452 (7.08%)	39/453 (8.61%)
Oedema peripheral ^† 1	24/452 (5.31%)	29/453 (6.40%)
Pyrexia ^† 1	39/452 (8.63%)	105/453 (23.18%)
Infections and infestations
Nasopharyngitis ^† 1	53/452 (11.73%)	24/453 (5.30%)
Upper respiratory tract infection ^† 1	43/452 (9.51%)	32/453 (7.06%)
Investigations
Alanine aminotransferase increased ^† 1	38/452 (8.41%)	88/453 (19.43%)
Amylase increased ^† 1	29/452 (6.42%)	26/453 (5.74%)
Aspartate aminotransferase increased ^† 1	31/452 (6.86%)	75/453 (16.56%)
Blood alkaline phosphatase increased ^† 1	4/452 (0.88%)	26/453 (5.74%)
Lipase increased ^† 1	36/452 (7.96%)	41/453 (9.05%)
Weight decreased ^† 1	11/452 (2.43%)	35/453 (7.73%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	43/452 (9.51%)	69/453 (15.23%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	91/452 (20.13%)	72/453 (15.89%)
Back pain ^† 1	48/452 (10.62%)	46/453 (10.15%)
Musculoskeletal pain ^† 1	23/452 (5.09%)	17/453 (3.75%)
Myalgia ^† 1	62/452 (13.72%)	35/453 (7.73%)
Pain in extremity ^† 1	42/452 (9.29%)	35/453 (7.73%)
Nervous system disorders
Dizziness ^† 1	46/452 (10.18%)	39/453 (8.61%)
Headache ^† 1	109/452 (24.12%)	148/453 (32.67%)
Psychiatric disorders
Anxiety ^† 1	25/452 (5.53%)	21/453 (4.64%)
Insomnia ^† 1	35/452 (7.74%)	43/453 (9.49%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	84/452 (18.58%)	83/453 (18.32%)
Dyspnoea ^† 1	34/452 (7.52%)	45/453 (9.93%)
Nasal congestion ^† 1	24/452 (5.31%)	17/453 (3.75%)
Oropharyngeal pain ^† 1	30/452 (6.64%)	37/453 (8.17%)
Skin and subcutaneous tissue disorders
Erythema ^† 1	33/452 (7.30%)	23/453 (5.08%)
Pruritus ^† 1	137/452 (30.31%)	179/453 (39.51%)
Rash ^† 1	122/452 (26.99%)	167/453 (36.87%)
Rash maculo-papular ^† 1	27/452 (5.97%)	52/453 (11.48%)
Vascular disorders
Hypertension ^† 1	33/452 (7.30%)	24/453 (5.30%)
1 Term from vocabulary, 22.1 † 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.

Results Point of Contact

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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):

Larkin J, Weber J, Del Vecchio M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, Middleton MR, De la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Long GV, Lobo M, Askelson M, Ascierto PA, Mandala M. Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria. Eur J Cancer. 2022 Sep;173:285-296. doi: 10.1016/j.ejca.2022.06.041. Epub 2022 Aug 11.

Weber JS, Ascierto PA, Middleton MR, Hennicken D, Zoffoli R, Pieters A, Amadi A, Kupas K, Kotapati S, Moshyk A, Schadendorf D. Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma. Eur J Cancer. 2021 Nov;158:225-233. doi: 10.1016/j.ejca.2021.08.028. Epub 2021 Oct 15.

Mandala M, Larkin J, Ascierto PA, Del Vecchio M, Gogas H, Cowey CL, Arance A, Dalle S, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, Lutzky J, De La Cruz-Merino L, Atkinson V, Arenberger P, Hill A, Fecher L, Millward M, Khushalani NI, de Pril V, Lobo M, Weber J. Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. J Immunother Cancer. 2021 Aug;9(8):e003188. doi: 10.1136/jitc-2021-003188. Erratum In: J Immunother Cancer. 2021 Nov;9(11):

Ascierto PA, Del Vecchio M, Mandala M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Maio M, Middleton MR, de la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Lobo M, de Pril V, Loffredo J, Larkin J, Weber J. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1465-1477. doi: 10.1016/S1470-2045(20)30494-0. Epub 2020 Sep 19. Erratum In: Lancet Oncol. 2021 Oct;22(10):e428.

Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, Dalle S, Schenker M, Chiarion-Sileni V, Marquez-Rodas I, Grob JJ, Butler MO, Middleton MR, Maio M, Atkinson V, Queirolo P, Gonzalez R, Kudchadkar RR, Smylie M, Meyer N, Mortier L, Atkins MB, Long GV, Bhatia S, Lebbe C, Rutkowski P, Yokota K, Yamazaki N, Kim TM, de Pril V, Sabater J, Qureshi A, Larkin J, Ascierto PA; CheckMate 238 Collaborators. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017 Nov 9;377(19):1824-1835. doi: 10.1056/NEJMoa1709030. Epub 2017 Sep 10.

Layout table for additonal information

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02388906
Other Study ID Numbers:	CA209-238 2014-002351-26 ( EudraCT Number )
First Submitted:	March 10, 2015
First Posted:	March 17, 2015
Results First Submitted:	April 16, 2021
Results First Posted:	June 15, 2021
Last Update Posted:	January 10, 2024

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