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Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02231749
Recruitment Status : Active, not recruiting
First Posted : September 4, 2014
Results First Posted : October 16, 2018
Last Update Posted : September 11, 2020
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: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma
Interventions Biological: Nivolumab
Biological: Ipilimumab
Drug: Sunitinib
Enrollment 1390
Recruitment Details  
Pre-assignment Details A total 1390 patients were enrolled in the study. Of these, 1096 were randomized. Of those randomized, 1082 received treatment (547 with Nivo+Ipi and 535 with Sunitinib). 240 patients who were not randomized because they no longer met study criteria, 24 withdrew consent, 4 for Adverse Events, 4 for Death, 4 for Poor Compliance, and 18 other.
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Period Title: Overall Study
Started [1] 550 546
Received Treatment 547 535
Completed [2] 128 97
Not Completed 422 449
Reason Not Completed
Disease progression             229             297
Study Drug Toxicity             134             63
Death             1             1
AE unrelated to Study drug             32             31
Participant's request to discontinue             10             21
Participant withdrew Consent             8             15
Lost to Follow-up             1             2
Maximum Clinical Benefit             5             8
Poor/Non-Compliance             0             3
Pregnancy             1             0
other             0             8
No longer meets Study Criteria             1             0
[1]
Started = Randomized
[2]
Completed = Continuing in the Treatment Period
Arm/Group Title Nivolumab + Ipilimumab Sunitinib Total
Hide Arm/Group Description Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks Total of all reporting groups
Overall Number of Baseline Participants 550 546 1096
Hide Baseline Analysis Population Description
All Randomized Participants
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 550 participants 546 participants 1096 participants
61.1  (9.76) 60.7  (10.10) 60.9  (9.93)
[1]
Measure Analysis Population Description: All Randomized
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 550 participants 546 participants 1096 participants
Female
137
  24.9%
151
  27.7%
288
  26.3%
Male
413
  75.1%
395
  72.3%
808
  73.7%
[1]
Measure Analysis Population Description: All Randomized Participants
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 550 participants 546 participants 1096 participants
Hispanic or Latino
12
   2.2%
17
   3.1%
29
   2.6%
Not Hispanic or Latino
264
  48.0%
253
  46.3%
517
  47.2%
Unknown or Not Reported
274
  49.8%
276
  50.5%
550
  50.2%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 550 participants 546 participants 1096 participants
White
486
  88.4%
483
  88.5%
969
  88.4%
Black or African American
7
   1.3%
6
   1.1%
13
   1.2%
Asian
46
   8.4%
47
   8.6%
93
   8.5%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other
10
   1.8%
10
   1.8%
20
   1.8%
Not Reported
1
   0.2%
0
   0.0%
1
   0.1%
[1]
Measure Analysis Population Description: All Randomized Participants
1.Primary Outcome
Title Investigator-assessed Objective Response Rate(ORR) in Intermediate/Poor Risk Participants Per IRRC Using RECIST v1.1
Hide Description ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Intermediate/Poor-Risk Participants
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description:
Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Overall Number of Participants Analyzed 425 422
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.6
(36.9 to 46.5)
26.5
(22.4 to 31.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab + Ipilimumab, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method DerSimonian and Laird Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Difference
Estimated Value 16.0
Confidence Interval (2-Sided) 95%
9.8 to 22.2
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
Hide Description OS was defined as the time from randomization to the date of death from any cause. Survival time was censored at the date of last contact ("last known alive date") for subjects who were alive.
Time Frame From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Intermediate/Poor-Risk Participants
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description:
Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Overall Number of Participants Analyzed 425 422
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(28.16 to NA)
25.95 [1] 
(22.08 to NA)
[1]
The median for Overall Survival and Upper Limit have not been reached. There were an insufficient number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab + Ipilimumab, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 99.8%
0.44 to 0.89
Estimation Comments [Not Specified]
3.Primary Outcome
Title Progression-Free Survival (PFS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
Hide Description PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.
Time Frame From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Intermediate/Poor-Risk Participants
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description:
Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Overall Number of Participants Analyzed 425 422
Median (95% Confidence Interval)
Unit of Measure: months
11.56
(8.71 to 15.51)
8.38
(7.03 to 10.81)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab + Ipilimumab, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0331
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 99.1%
0.64 to 1.05
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Investigator-assessed Objective Response Rate(ORR) in Any Risk Participants Per IRRC Using RECIST v1.1
Hide Description ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description:
Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Overall Number of Participants Analyzed 550 546
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
38.7
(34.6 to 42.9)
32.2
(28.3 to 36.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab + Ipilimumab, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0191
Comments [Not Specified]
Method DerSimonian and Laird Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Difference
Estimated Value 7.2
Confidence Interval (2-Sided) 95%
1.8 to 12.7
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Overall Survival (OS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
Hide Description Overall survival is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time will be censored at the date of last contact ("last known alive date"). Overall survival will be censored for subjects at the date of randomization if they were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after subject's off-treatment date.
Time Frame From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description:
Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Overall Number of Participants Analyzed 550 546
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
32.92 [2] 
(NA to NA)
[1]
The median for Overall Survival, Lower limit, and Upper Limit have not been reached. There were an insufficient number of participants with events.
[2]
The Lower Limit and Upper Limit have not been reached. With only 1 participant at that time point, the variance is not estimable and so the Confidence Intervals were N/A.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab + Ipilimumab, Sunitinib
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 [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 99.8%
0.49 to 0.95
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Progression-Free Survival (PFS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
Hide Description PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.
Time Frame From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description:
Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
Overall Number of Participants Analyzed 550 546
Median (95% Confidence Interval)
Unit of Measure: months
12.42
(9.89 to 16.53)
12.32
(9.79 to 15.24)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab + Ipilimumab, Sunitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8498
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 99.1%
0.79 to 1.23
Estimation Comments [Not Specified]
Time Frame From first dose to 30 days after last dose of study therapy (assessed up to June 2017, approximately 31 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Nivolumab + Ipilimumab Sunitinib
Hide Arm/Group Description Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks

All-Cause Mortality
Nivolumab + Ipilimumab Sunitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   159/547 (29.07%)   202/535 (37.76%) 
Hide Serious Adverse Events
Nivolumab + Ipilimumab Sunitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   305/547 (55.76%)   213/535 (39.81%) 
Blood and lymphatic system disorders     
Anaemia  1  6/547 (1.10%)  7/535 (1.31%) 
Autoimmune neutropenia  1  1/547 (0.18%)  0/535 (0.00%) 
Pancytopenia  1  0/547 (0.00%)  1/535 (0.19%) 
Splenic lesion  1  0/547 (0.00%)  1/535 (0.19%) 
Thrombocytopenia  1  0/547 (0.00%)  1/535 (0.19%) 
Cardiac disorders     
Acute coronary syndrome  1  1/547 (0.18%)  1/535 (0.19%) 
Acute myocardial infarction  1  2/547 (0.37%)  0/535 (0.00%) 
Angina pectoris  1  1/547 (0.18%)  1/535 (0.19%) 
Arrhythmia  1  1/547 (0.18%)  1/535 (0.19%) 
Atrial fibrillation  1  2/547 (0.37%)  0/535 (0.00%) 
Cardiac arrest  1  3/547 (0.55%)  2/535 (0.37%) 
Cardiac failure  1  1/547 (0.18%)  1/535 (0.19%) 
Cardiac failure congestive  1  0/547 (0.00%)  3/535 (0.56%) 
Cardio-respiratory arrest  1  1/547 (0.18%)  0/535 (0.00%) 
Cardiopulmonary failure  1  1/547 (0.18%)  0/535 (0.00%) 
Cardiovascular disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Myocardial infarction  1  6/547 (1.10%)  1/535 (0.19%) 
Myocarditis  1  1/547 (0.18%)  0/535 (0.00%) 
Right ventricular failure  1  0/547 (0.00%)  1/535 (0.19%) 
Sinus node dysfunction  1  1/547 (0.18%)  0/535 (0.00%) 
Tachycardia  1  0/547 (0.00%)  1/535 (0.19%) 
Ear and labyrinth disorders     
Vertigo  1  1/547 (0.18%)  1/535 (0.19%) 
Endocrine disorders     
Adrenal insufficiency  1  10/547 (1.83%)  0/535 (0.00%) 
Adrenocortical insufficiency acute  1  2/547 (0.37%)  0/535 (0.00%) 
Adrenocorticotropic hormone deficiency  1  1/547 (0.18%)  0/535 (0.00%) 
Autoimmune hypothyroidism  1  1/547 (0.18%)  0/535 (0.00%) 
Basedow's disease  1  2/547 (0.37%)  0/535 (0.00%) 
Goitre  1  1/547 (0.18%)  0/535 (0.00%) 
Hyperthyroidism  1  3/547 (0.55%)  0/535 (0.00%) 
Hypophysitis  1  14/547 (2.56%)  0/535 (0.00%) 
Hypopituitarism  1  2/547 (0.37%)  0/535 (0.00%) 
Hypothalamo-pituitary disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Hypothyroidism  1  2/547 (0.37%)  1/535 (0.19%) 
Secondary adrenocortical insufficiency  1  2/547 (0.37%)  0/535 (0.00%) 
Steroid withdrawal syndrome  1  1/547 (0.18%)  0/535 (0.00%) 
Thyroiditis  1  3/547 (0.55%)  0/535 (0.00%) 
Eye disorders     
Diplopia  1  2/547 (0.37%)  0/535 (0.00%) 
Eye pain  1  1/547 (0.18%)  0/535 (0.00%) 
Inflammation of lacrimal passage  1  1/547 (0.18%)  0/535 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  5/547 (0.91%)  4/535 (0.75%) 
Abdominal pain upper  1  0/547 (0.00%)  1/535 (0.19%) 
Anal fistula  1  0/547 (0.00%)  1/535 (0.19%) 
Autoimmune colitis  1  1/547 (0.18%)  0/535 (0.00%) 
Colitis  1  10/547 (1.83%)  0/535 (0.00%) 
Diarrhoea  1  24/547 (4.39%)  3/535 (0.56%) 
Diarrhoea haemorrhagic  1  1/547 (0.18%)  0/535 (0.00%) 
Diverticular perforation  1  0/547 (0.00%)  1/535 (0.19%) 
Duodenal obstruction  1  1/547 (0.18%)  0/535 (0.00%) 
Duodenal ulcer  1  0/547 (0.00%)  1/535 (0.19%) 
Dysphagia  1  1/547 (0.18%)  0/535 (0.00%) 
Enterocolitis  1  1/547 (0.18%)  0/535 (0.00%) 
Gastric haemorrhage  1  0/547 (0.00%)  1/535 (0.19%) 
Gastric ulcer  1  1/547 (0.18%)  0/535 (0.00%) 
Gastric ulcer haemorrhage  1  0/547 (0.00%)  1/535 (0.19%) 
Gastritis  1  1/547 (0.18%)  1/535 (0.19%) 
Gastrointestinal haemorrhage  1  1/547 (0.18%)  4/535 (0.75%) 
Haemorrhoidal haemorrhage  1  0/547 (0.00%)  1/535 (0.19%) 
Ileus  1  1/547 (0.18%)  0/535 (0.00%) 
Intestinal obstruction  1  1/547 (0.18%)  0/535 (0.00%) 
Intestinal perforation  1  0/547 (0.00%)  1/535 (0.19%) 
Intussusception  1  0/547 (0.00%)  1/535 (0.19%) 
Large intestine perforation  1  0/547 (0.00%)  2/535 (0.37%) 
Lower gastrointestinal haemorrhage  1  1/547 (0.18%)  0/535 (0.00%) 
Nausea  1  8/547 (1.46%)  2/535 (0.37%) 
Oesophagitis  1  1/547 (0.18%)  0/535 (0.00%) 
Oesophagitis ulcerative  1  1/547 (0.18%)  0/535 (0.00%) 
Pancreatitis  1  3/547 (0.55%)  4/535 (0.75%) 
Pancreatitis acute  1  0/547 (0.00%)  1/535 (0.19%) 
Rectal haemorrhage  1  1/547 (0.18%)  2/535 (0.37%) 
Retroperitoneal haemorrhage  1  0/547 (0.00%)  1/535 (0.19%) 
Small intestinal obstruction  1  0/547 (0.00%)  1/535 (0.19%) 
Stomatitis  1  0/547 (0.00%)  2/535 (0.37%) 
Upper gastrointestinal haemorrhage  1  0/547 (0.00%)  2/535 (0.37%) 
Vomiting  1  5/547 (0.91%)  4/535 (0.75%) 
General disorders     
Asthenia  1  1/547 (0.18%)  4/535 (0.75%) 
Chest discomfort  1  1/547 (0.18%)  0/535 (0.00%) 
Chest pain  1  1/547 (0.18%)  2/535 (0.37%) 
Death  1  1/547 (0.18%)  0/535 (0.00%) 
Fatigue  1  4/547 (0.73%)  5/535 (0.93%) 
Gait disturbance  1  0/547 (0.00%)  1/535 (0.19%) 
General physical health deterioration  1  4/547 (0.73%)  4/535 (0.75%) 
Influenza like illness  1  1/547 (0.18%)  0/535 (0.00%) 
Malaise  1  2/547 (0.37%)  2/535 (0.37%) 
Mucosal inflammation  1  0/547 (0.00%)  1/535 (0.19%) 
Oedema peripheral  1  1/547 (0.18%)  1/535 (0.19%) 
Pain  1  0/547 (0.00%)  2/535 (0.37%) 
Pyrexia  1  18/547 (3.29%)  9/535 (1.68%) 
Sudden death  1  0/547 (0.00%)  1/535 (0.19%) 
Hepatobiliary disorders     
Biliary colic  1  0/547 (0.00%)  2/535 (0.37%) 
Cholangitis  1  0/547 (0.00%)  1/535 (0.19%) 
Cholangitis acute  1  0/547 (0.00%)  1/535 (0.19%) 
Cholecystitis  1  0/547 (0.00%)  3/535 (0.56%) 
Cholelithiasis  1  0/547 (0.00%)  1/535 (0.19%) 
Gallbladder disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Gallbladder obstruction  1  0/547 (0.00%)  1/535 (0.19%) 
Hepatic function abnormal  1  1/547 (0.18%)  0/535 (0.00%) 
Hepatic pain  1  0/547 (0.00%)  1/535 (0.19%) 
Hepatitis  1  3/547 (0.55%)  0/535 (0.00%) 
Hepatitis acute  1  1/547 (0.18%)  0/535 (0.00%) 
Hepatitis toxic  1  1/547 (0.18%)  0/535 (0.00%) 
Hepatotoxicity  1  1/547 (0.18%)  0/535 (0.00%) 
Jaundice  1  0/547 (0.00%)  1/535 (0.19%) 
Jaundice cholestatic  1  1/547 (0.18%)  2/535 (0.37%) 
Portal vein thrombosis  1  1/547 (0.18%)  0/535 (0.00%) 
Immune system disorders     
Anaphylactic reaction  1  0/547 (0.00%)  1/535 (0.19%) 
Autoimmune disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Contrast media allergy  1  3/547 (0.55%)  0/535 (0.00%) 
Contrast media reaction  1  2/547 (0.37%)  0/535 (0.00%) 
Infections and infestations     
Abdominal infection  1  0/547 (0.00%)  1/535 (0.19%) 
Appendicitis  1  2/547 (0.37%)  1/535 (0.19%) 
Bronchitis  1  3/547 (0.55%)  0/535 (0.00%) 
Cellulitis  1  3/547 (0.55%)  0/535 (0.00%) 
Cholecystitis infective  1  0/547 (0.00%)  1/535 (0.19%) 
Diarrhoea infectious  1  1/547 (0.18%)  0/535 (0.00%) 
Diverticulitis  1  1/547 (0.18%)  0/535 (0.00%) 
Encephalitis  1  1/547 (0.18%)  0/535 (0.00%) 
Epididymitis  1  0/547 (0.00%)  1/535 (0.19%) 
Gastroenteritis  1  3/547 (0.55%)  1/535 (0.19%) 
Herpes zoster disseminated  1  1/547 (0.18%)  0/535 (0.00%) 
Infected skin ulcer  1  0/547 (0.00%)  1/535 (0.19%) 
Infection  1  0/547 (0.00%)  2/535 (0.37%) 
Influenza  1  1/547 (0.18%)  2/535 (0.37%) 
Laryngitis  1  1/547 (0.18%)  0/535 (0.00%) 
Lower respiratory tract infection  1  2/547 (0.37%)  2/535 (0.37%) 
Lung abscess  1  0/547 (0.00%)  1/535 (0.19%) 
Lung infection  1  2/547 (0.37%)  1/535 (0.19%) 
Meningitis aseptic  1  2/547 (0.37%)  0/535 (0.00%) 
Peritonsillar abscess  1  0/547 (0.00%)  1/535 (0.19%) 
Pneumonia  1  17/547 (3.11%)  8/535 (1.50%) 
Pulmonary sepsis  1  1/547 (0.18%)  0/535 (0.00%) 
Rectal abscess  1  0/547 (0.00%)  1/535 (0.19%) 
Respiratory syncytial virus infection  1  1/547 (0.18%)  0/535 (0.00%) 
Respiratory tract infection  1  1/547 (0.18%)  0/535 (0.00%) 
Sepsis  1  5/547 (0.91%)  6/535 (1.12%) 
Septic shock  1  2/547 (0.37%)  0/535 (0.00%) 
Soft tissue infection  1  1/547 (0.18%)  0/535 (0.00%) 
Upper respiratory tract infection  1  1/547 (0.18%)  0/535 (0.00%) 
Urinary tract infection  1  6/547 (1.10%)  0/535 (0.00%) 
Urosepsis  1  1/547 (0.18%)  1/535 (0.19%) 
Viral infection  1  1/547 (0.18%)  0/535 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1  1/547 (0.18%)  0/535 (0.00%) 
Drug administration error  1  1/547 (0.18%)  0/535 (0.00%) 
Fall  1  0/547 (0.00%)  1/535 (0.19%) 
Femur fracture  1  1/547 (0.18%)  1/535 (0.19%) 
Fracture  1  0/547 (0.00%)  1/535 (0.19%) 
Hip fracture  1  0/547 (0.00%)  1/535 (0.19%) 
Humerus fracture  1  0/547 (0.00%)  2/535 (0.37%) 
Incisional hernia  1  1/547 (0.18%)  0/535 (0.00%) 
Injury  1  0/547 (0.00%)  1/535 (0.19%) 
Joint dislocation  1  1/547 (0.18%)  0/535 (0.00%) 
Lumbar vertebral fracture  1  0/547 (0.00%)  1/535 (0.19%) 
Pneumonitis chemical  1  1/547 (0.18%)  0/535 (0.00%) 
Postoperative hernia  1  1/547 (0.18%)  0/535 (0.00%) 
Seroma  1  0/547 (0.00%)  1/535 (0.19%) 
Subarachnoid haemorrhage  1  0/547 (0.00%)  1/535 (0.19%) 
Upper limb fracture  1  0/547 (0.00%)  1/535 (0.19%) 
Wound  1  1/547 (0.18%)  0/535 (0.00%) 
Wrist fracture  1  0/547 (0.00%)  1/535 (0.19%) 
Investigations     
Activated partial thromboplastin time prolonged  1  0/547 (0.00%)  1/535 (0.19%) 
Alanine aminotransferase increased  1  9/547 (1.65%)  0/535 (0.00%) 
Aspartate aminotransferase increased  1  4/547 (0.73%)  0/535 (0.00%) 
Blood bilirubin increased  1  0/547 (0.00%)  1/535 (0.19%) 
Blood creatinine increased  1  5/547 (0.91%)  1/535 (0.19%) 
Blood potassium increased  1  0/547 (0.00%)  1/535 (0.19%) 
Lipase increased  1  1/547 (0.18%)  0/535 (0.00%) 
Pancreatic enzymes increased  1  1/547 (0.18%)  0/535 (0.00%) 
Platelet count decreased  1  0/547 (0.00%)  4/535 (0.75%) 
Transaminases increased  1  3/547 (0.55%)  0/535 (0.00%) 
Troponin increased  1  0/547 (0.00%)  1/535 (0.19%) 
Metabolism and nutrition disorders     
Acidosis  1  1/547 (0.18%)  0/535 (0.00%) 
Decreased appetite  1  2/547 (0.37%)  0/535 (0.00%) 
Dehydration  1  7/547 (1.28%)  8/535 (1.50%) 
Diabetes mellitus  1  2/547 (0.37%)  0/535 (0.00%) 
Diabetes mellitus inadequate control  1  1/547 (0.18%)  0/535 (0.00%) 
Diabetic ketoacidosis  1  2/547 (0.37%)  0/535 (0.00%) 
Fluid overload  1  1/547 (0.18%)  0/535 (0.00%) 
Fulminant type 1 diabetes mellitus  1  2/547 (0.37%)  0/535 (0.00%) 
Hypercalcaemia  1  4/547 (0.73%)  3/535 (0.56%) 
Hyperglycaemia  1  6/547 (1.10%)  1/535 (0.19%) 
Hyperkalaemia  1  1/547 (0.18%)  2/535 (0.37%) 
Hypoglycaemia  1  3/547 (0.55%)  3/535 (0.56%) 
Hypokalaemia  1  2/547 (0.37%)  0/535 (0.00%) 
Hypomagnesaemia  1  0/547 (0.00%)  2/535 (0.37%) 
Hyponatraemia  1  9/547 (1.65%)  5/535 (0.93%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/547 (0.73%)  0/535 (0.00%) 
Arthritis  1  1/547 (0.18%)  0/535 (0.00%) 
Back pain  1  4/547 (0.73%)  4/535 (0.75%) 
Fistula  1  1/547 (0.18%)  0/535 (0.00%) 
Flank pain  1  1/547 (0.18%)  0/535 (0.00%) 
Groin pain  1  1/547 (0.18%)  0/535 (0.00%) 
Muscular weakness  1  1/547 (0.18%)  1/535 (0.19%) 
Musculoskeletal pain  1  0/547 (0.00%)  1/535 (0.19%) 
Myalgia  1  1/547 (0.18%)  0/535 (0.00%) 
Neck pain  1  0/547 (0.00%)  2/535 (0.37%) 
Osteolysis  1  1/547 (0.18%)  0/535 (0.00%) 
Osteonecrosis  1  0/547 (0.00%)  1/535 (0.19%) 
Osteonecrosis of jaw  1  0/547 (0.00%)  1/535 (0.19%) 
Pain in extremity  1  1/547 (0.18%)  0/535 (0.00%) 
Pathological fracture  1  3/547 (0.55%)  0/535 (0.00%) 
Rhabdomyolysis  1  1/547 (0.18%)  0/535 (0.00%) 
Synovitis  1  1/547 (0.18%)  0/535 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/547 (0.18%)  3/535 (0.56%) 
Brain neoplasm  1  1/547 (0.18%)  0/535 (0.00%) 
Cancer pain  1  1/547 (0.18%)  1/535 (0.19%) 
Gastric adenoma  1  1/547 (0.18%)  0/535 (0.00%) 
Malignant neoplasm progression  1  22/547 (4.02%)  31/535 (5.79%) 
Malignant pleural effusion  1  1/547 (0.18%)  0/535 (0.00%) 
Metastases to bone  1  2/547 (0.37%)  1/535 (0.19%) 
Metastases to central nervous system  1  2/547 (0.37%)  3/535 (0.56%) 
Metastatic neoplasm  1  0/547 (0.00%)  1/535 (0.19%) 
Metastatic renal cell carcinoma  1  0/547 (0.00%)  1/535 (0.19%) 
Prostate cancer  1  0/547 (0.00%)  1/535 (0.19%) 
Small intestine adenocarcinoma  1  1/547 (0.18%)  0/535 (0.00%) 
Squamous cell carcinoma  1  0/547 (0.00%)  1/535 (0.19%) 
Tumour haemorrhage  1  1/547 (0.18%)  1/535 (0.19%) 
Tumour pain  1  1/547 (0.18%)  0/535 (0.00%) 
Nervous system disorders     
Aphasia  1  1/547 (0.18%)  0/535 (0.00%) 
Brain oedema  1  1/547 (0.18%)  0/535 (0.00%) 
Central nervous system lesion  1  1/547 (0.18%)  0/535 (0.00%) 
Cerebral haemorrhage  1  2/547 (0.37%)  0/535 (0.00%) 
Cerebral infarction  1  3/547 (0.55%)  0/535 (0.00%) 
Cerebrovascular accident  1  0/547 (0.00%)  2/535 (0.37%) 
Cervical cord compression  1  0/547 (0.00%)  1/535 (0.19%) 
Dysarthria  1  0/547 (0.00%)  1/535 (0.19%) 
Embolic cerebral infarction  1  1/547 (0.18%)  0/535 (0.00%) 
Encephalopathy  1  1/547 (0.18%)  0/535 (0.00%) 
Facial nerve disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Facial paralysis  1  1/547 (0.18%)  0/535 (0.00%) 
Facial paresis  1  1/547 (0.18%)  0/535 (0.00%) 
Haemorrhage intracranial  1  1/547 (0.18%)  1/535 (0.19%) 
Headache  1  3/547 (0.55%)  1/535 (0.19%) 
Iiird nerve paralysis  1  1/547 (0.18%)  0/535 (0.00%) 
Intracranial aneurysm  1  0/547 (0.00%)  1/535 (0.19%) 
Intracranial pressure increased  1  1/547 (0.18%)  0/535 (0.00%) 
Ischaemic stroke  1  1/547 (0.18%)  0/535 (0.00%) 
Myasthenia gravis  1  1/547 (0.18%)  0/535 (0.00%) 
Neuropathy peripheral  1  1/547 (0.18%)  0/535 (0.00%) 
Paraesthesia  1  1/547 (0.18%)  0/535 (0.00%) 
Paraparesis  1  1/547 (0.18%)  0/535 (0.00%) 
Peripheral motor neuropathy  1  2/547 (0.37%)  0/535 (0.00%) 
Polyneuropathy  1  1/547 (0.18%)  0/535 (0.00%) 
Seizure  1  3/547 (0.55%)  0/535 (0.00%) 
Somnolence  1  0/547 (0.00%)  1/535 (0.19%) 
Speech disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Spinal cord compression  1  2/547 (0.37%)  1/535 (0.19%) 
Syncope  1  2/547 (0.37%)  1/535 (0.19%) 
Thecal sac compression  1  0/547 (0.00%)  1/535 (0.19%) 
Transient ischaemic attack  1  1/547 (0.18%)  1/535 (0.19%) 
Visual field defect  1  0/547 (0.00%)  1/535 (0.19%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  0/547 (0.00%)  1/535 (0.19%) 
Product Issues     
Device breakage  1  1/547 (0.18%)  0/535 (0.00%) 
Psychiatric disorders     
Confusional state  1  6/547 (1.10%)  0/535 (0.00%) 
Delirium  1  1/547 (0.18%)  1/535 (0.19%) 
Depression  1  0/547 (0.00%)  1/535 (0.19%) 
Suicide attempt  1  1/547 (0.18%)  0/535 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  8/547 (1.46%)  8/535 (1.50%) 
Autoimmune nephritis  1  1/547 (0.18%)  0/535 (0.00%) 
Haematuria  1  2/547 (0.37%)  8/535 (1.50%) 
Micturition urgency  1  1/547 (0.18%)  0/535 (0.00%) 
Nephritis  1  1/547 (0.18%)  0/535 (0.00%) 
Polyuria  1  1/547 (0.18%)  0/535 (0.00%) 
Renal failure  1  1/547 (0.18%)  3/535 (0.56%) 
Renal impairment  1  1/547 (0.18%)  2/535 (0.37%) 
Renal injury  1  2/547 (0.37%)  0/535 (0.00%) 
Renal mass  1  0/547 (0.00%)  1/535 (0.19%) 
Tubulointerstitial nephritis  1  0/547 (0.00%)  1/535 (0.19%) 
Urinary retention  1  1/547 (0.18%)  0/535 (0.00%) 
Urinary tract obstruction  1  2/547 (0.37%)  0/535 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst  1  0/547 (0.00%)  1/535 (0.19%) 
Prostatitis  1  1/547 (0.18%)  0/535 (0.00%) 
Uterine haemorrhage  1  0/547 (0.00%)  1/535 (0.19%) 
Respiratory, thoracic and mediastinal disorders     
Acquired diaphragmatic eventration  1  0/547 (0.00%)  1/535 (0.19%) 
Acute respiratory failure  1  1/547 (0.18%)  0/535 (0.00%) 
Asthma  1  0/547 (0.00%)  1/535 (0.19%) 
Bronchial obstruction  1  1/547 (0.18%)  1/535 (0.19%) 
Chronic obstructive pulmonary disease  1  2/547 (0.37%)  0/535 (0.00%) 
Chylothorax  1  1/547 (0.18%)  0/535 (0.00%) 
Cough  1  2/547 (0.37%)  0/535 (0.00%) 
Dyspnoea  1  9/547 (1.65%)  9/535 (1.68%) 
Epistaxis  1  0/547 (0.00%)  3/535 (0.56%) 
Haemoptysis  1  0/547 (0.00%)  3/535 (0.56%) 
Hydrothorax  1  0/547 (0.00%)  1/535 (0.19%) 
Hypoxia  1  0/547 (0.00%)  1/535 (0.19%) 
Interstitial lung disease  1  1/547 (0.18%)  0/535 (0.00%) 
Laryngeal oedema  1  0/547 (0.00%)  1/535 (0.19%) 
Lung disorder  1  1/547 (0.18%)  0/535 (0.00%) 
Orthopnoea  1  0/547 (0.00%)  1/535 (0.19%) 
Pleural effusion  1  7/547 (1.28%)  9/535 (1.68%) 
Pneumonitis  1  15/547 (2.74%)  1/535 (0.19%) 
Pneumothorax  1  1/547 (0.18%)  0/535 (0.00%) 
Pulmonary embolism  1  4/547 (0.73%)  3/535 (0.56%) 
Pulmonary haemorrhage  1  2/547 (0.37%)  1/535 (0.19%) 
Reflux laryngitis  1  0/547 (0.00%)  1/535 (0.19%) 
Respiratory failure  1  2/547 (0.37%)  0/535 (0.00%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  0/547 (0.00%)  1/535 (0.19%) 
Drug eruption  1  1/547 (0.18%)  0/535 (0.00%) 
Erythema multiforme  1  0/547 (0.00%)  1/535 (0.19%) 
Haemorrhage subcutaneous  1  1/547 (0.18%)  0/535 (0.00%) 
Pruritus  1  1/547 (0.18%)  0/535 (0.00%) 
Rash  1  2/547 (0.37%)  0/535 (0.00%) 
Rash maculo-papular  1  2/547 (0.37%)  0/535 (0.00%) 
Stevens-johnson syndrome  1  1/547 (0.18%)  0/535 (0.00%) 
Social circumstances     
Immobile  1  1/547 (0.18%)  0/535 (0.00%) 
Vascular disorders     
Angiopathy  1  1/547 (0.18%)  0/535 (0.00%) 
Deep vein thrombosis  1  1/547 (0.18%)  3/535 (0.56%) 
Embolism  1  2/547 (0.37%)  1/535 (0.19%) 
Haematoma  1  0/547 (0.00%)  1/535 (0.19%) 
Hypertension  1  0/547 (0.00%)  3/535 (0.56%) 
Hypotension  1  4/547 (0.73%)  2/535 (0.37%) 
Orthostatic hypotension  1  1/547 (0.18%)  0/535 (0.00%) 
Shock  1  1/547 (0.18%)  0/535 (0.00%) 
Subclavian vein occlusion  1  1/547 (0.18%)  0/535 (0.00%) 
Vein rupture  1  1/547 (0.18%)  0/535 (0.00%) 
Venous thrombosis  1  1/547 (0.18%)  0/535 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nivolumab + Ipilimumab Sunitinib
Affected / at Risk (%) Affected / at Risk (%)
Total   530/547 (96.89%)   522/535 (97.57%) 
Blood and lymphatic system disorders     
Anaemia  1  71/547 (12.98%)  108/535 (20.19%) 
Leukopenia  1  1/547 (0.18%)  31/535 (5.79%) 
Neutropenia  1  3/547 (0.55%)  73/535 (13.64%) 
Thrombocytopenia  1  6/547 (1.10%)  98/535 (18.32%) 
Endocrine disorders     
Hyperthyroidism  1  63/547 (11.52%)  16/535 (2.99%) 
Hypothyroidism  1  94/547 (17.18%)  144/535 (26.92%) 
Eye disorders     
Vision blurred  1  28/547 (5.12%)  10/535 (1.87%) 
Gastrointestinal disorders     
Abdominal distension  1  14/547 (2.56%)  27/535 (5.05%) 
Abdominal pain  1  69/547 (12.61%)  76/535 (14.21%) 
Abdominal pain upper  1  26/547 (4.75%)  44/535 (8.22%) 
Constipation  1  93/547 (17.00%)  94/535 (17.57%) 
Diarrhoea  1  198/547 (36.20%)  310/535 (57.94%) 
Dry mouth  1  35/547 (6.40%)  37/535 (6.92%) 
Dyspepsia  1  29/547 (5.30%)  112/535 (20.93%) 
Flatulence  1  7/547 (1.28%)  31/535 (5.79%) 
Gastrooesophageal reflux disease  1  11/547 (2.01%)  67/535 (12.52%) 
Haemorrhoids  1  12/547 (2.19%)  27/535 (5.05%) 
Nausea  1  161/547 (29.43%)  230/535 (42.99%) 
Oral pain  1  2/547 (0.37%)  30/535 (5.61%) 
Stomatitis  1  29/547 (5.30%)  152/535 (28.41%) 
Toothache  1  9/547 (1.65%)  27/535 (5.05%) 
Vomiting  1  108/547 (19.74%)  148/535 (27.66%) 
General disorders     
Asthenia  1  88/547 (16.09%)  99/535 (18.50%) 
Chest pain  1  23/547 (4.20%)  27/535 (5.05%) 
Chills  1  31/547 (5.67%)  42/535 (7.85%) 
Fatigue  1  246/547 (44.97%)  291/535 (54.39%) 
Influenza like illness  1  46/547 (8.41%)  27/535 (5.05%) 
Malaise  1  12/547 (2.19%)  28/535 (5.23%) 
Mucosal inflammation  1  18/547 (3.29%)  156/535 (29.16%) 
Oedema peripheral  1  75/547 (13.71%)  66/535 (12.34%) 
Pain  1  33/547 (6.03%)  45/535 (8.41%) 
Pyrexia  1  126/547 (23.03%)  85/535 (15.89%) 
Infections and infestations     
Upper respiratory tract infection  1  34/547 (6.22%)  35/535 (6.54%) 
Urinary tract infection  1  29/547 (5.30%)  24/535 (4.49%) 
Viral upper respiratory tract infection  1  46/547 (8.41%)  21/535 (3.93%) 
Investigations     
Alanine aminotransferase increased  1  63/547 (11.52%)  60/535 (11.21%) 
Amylase increased  1  76/547 (13.89%)  42/535 (7.85%) 
Aspartate aminotransferase increased  1  69/547 (12.61%)  57/535 (10.65%) 
Blood alkaline phosphatase increased  1  32/547 (5.85%)  24/535 (4.49%) 
Blood creatinine increased  1  65/547 (11.88%)  49/535 (9.16%) 
Blood thyroid stimulating hormone increased  1  12/547 (2.19%)  32/535 (5.98%) 
Lipase increased  1  96/547 (17.55%)  65/535 (12.15%) 
Neutrophil count decreased  1  5/547 (0.91%)  40/535 (7.48%) 
Platelet count decreased  1  9/547 (1.65%)  76/535 (14.21%) 
Weight decreased  1  47/547 (8.59%)  41/535 (7.66%) 
White blood cell count decreased  1  6/547 (1.10%)  41/535 (7.66%) 
Metabolism and nutrition disorders     
Decreased appetite  1  114/547 (20.84%)  156/535 (29.16%) 
Dehydration  1  28/547 (5.12%)  22/535 (4.11%) 
Hyperglycaemia  1  54/547 (9.87%)  23/535 (4.30%) 
Hyperkalaemia  1  36/547 (6.58%)  21/535 (3.93%) 
Hypomagnesaemia  1  17/547 (3.11%)  32/535 (5.98%) 
Hyponatraemia  1  33/547 (6.03%)  28/535 (5.23%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  122/547 (22.30%)  83/535 (15.51%) 
Back pain  1  87/547 (15.90%)  89/535 (16.64%) 
Muscle spasms  1  34/547 (6.22%)  28/535 (5.23%) 
Musculoskeletal pain  1  36/547 (6.58%)  33/535 (6.17%) 
Myalgia  1  64/547 (11.70%)  34/535 (6.36%) 
Pain in extremity  1  62/547 (11.33%)  76/535 (14.21%) 
Nervous system disorders     
Dizziness  1  61/547 (11.15%)  61/535 (11.40%) 
Dysgeusia  1  40/547 (7.31%)  185/535 (34.58%) 
Headache  1  102/547 (18.65%)  120/535 (22.43%) 
Paraesthesia  1  33/547 (6.03%)  29/535 (5.42%) 
Psychiatric disorders     
Anxiety  1  29/547 (5.30%)  21/535 (3.93%) 
Insomnia  1  58/547 (10.60%)  35/535 (6.54%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  144/547 (26.33%)  125/535 (23.36%) 
Dysphonia  1  18/547 (3.29%)  28/535 (5.23%) 
Dyspnoea  1  95/547 (17.37%)  92/535 (17.20%) 
Epistaxis  1  7/547 (1.28%)  75/535 (14.02%) 
Oropharyngeal pain  1  26/547 (4.75%)  40/535 (7.48%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  5/547 (0.91%)  27/535 (5.05%) 
Dry skin  1  55/547 (10.05%)  53/535 (9.91%) 
Hair colour changes  1  0/547 (0.00%)  32/535 (5.98%) 
Palmar-plantar erythrodysaesthesia syndrome  1  9/547 (1.65%)  237/535 (44.30%) 
Pruritus  1  180/547 (32.91%)  58/535 (10.84%) 
Rash  1  139/547 (25.41%)  84/535 (15.70%) 
Rash maculo-papular  1  55/547 (10.05%)  28/535 (5.23%) 
Skin discolouration  1  3/547 (0.55%)  27/535 (5.05%) 
Yellow skin  1  0/547 (0.00%)  45/535 (8.41%) 
Vascular disorders     
Hypertension  1  52/547 (9.51%)  230/535 (42.99%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
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
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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):
Motzer RJ, Rini BI, McDermott DF, Arén Frontera O, Hammers HJ, Carducci MA, Salman P, Escudier B, Beuselinck B, Amin A, Porta C, George S, Neiman V, Bracarda S, Tykodi SS, Barthélémy P, Leibowitz-Amit R, Plimack ER, Oosting SF, Redman B, Melichar B, Powles T, Nathan P, Oudard S, Pook D, Choueiri TK, Donskov F, Grimm MO, Gurney H, Heng DYC, Kollmannsberger CK, Harrison MR, Tomita Y, Duran I, Grünwald V, McHenry MB, Mekan S, Tannir NM; CheckMate 214 investigators. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019 Oct;20(10):1370-1385. doi: 10.1016/S1470-2045(19)30413-9. Epub 2019 Aug 16. Erratum in: Lancet Oncol. 2019 Aug 21;:. Erratum in: Lancet Oncol. 2020 Jun;21(6):e304. Lancet Oncol. 2020 Nov;21(11):e518.
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02231749    
Other Study ID Numbers: CA209-214
2014-001750-42 ( EudraCT Number )
First Submitted: September 1, 2014
First Posted: September 4, 2014
Results First Submitted: June 21, 2018
Results First Posted: October 16, 2018
Last Update Posted: September 11, 2020