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A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER)

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: NCT03141177
Recruitment Status : Active, not recruiting
First Posted : May 4, 2017
Results First Posted : April 26, 2022
Last Update Posted : September 16, 2022
Sponsor:
Collaborators:
Exelixis
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
Condition Renal Cell Carcinoma
Interventions Biological: Nivolumab
Drug: Cabozantinib
Drug: Sunitinib
Biological: Ipilimumab
Enrollment 701
Recruitment Details  
Pre-assignment Details 701 participants randomized and 690 treated.
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Period Title: Overall Study
Started [1] 323 50 328
Treated [2] 320 50 320
Completed [3] 242 34 210
Not Completed 81 16 118
Reason Not Completed
Death             62             13             84
Participant withdrew consent             9             2             13
Not reported             1             0             1
Lost to Follow-up             2             1             1
Other reasons             4             0             11
Participants did not start treatment period             3             0             8
[1]
Started=Randomized
[2]
Treated=Started treatment period
[3]
Completed=Continuing in the Study
Arm/Group Title Treatment A Treatment B Treatment C Total
Hide Arm/Group Description Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle Total of all reporting groups
Overall Number of Baseline Participants 323 50 328 701
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 323 participants 50 participants 328 participants 701 participants
61.4  (10.2) 60.3  (9.5) 60.4  (10.6) 60.9  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 50 participants 328 participants 701 participants
Female
74
  22.9%
16
  32.0%
96
  29.3%
186
  26.5%
Male
249
  77.1%
34
  68.0%
232
  70.7%
515
  73.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 50 participants 328 participants 701 participants
Hispanic or Latino
38
  11.8%
13
  26.0%
39
  11.9%
90
  12.8%
Not Hispanic or Latino
149
  46.1%
19
  38.0%
151
  46.0%
319
  45.5%
Unknown or Not Reported
136
  42.1%
18
  36.0%
138
  42.1%
292
  41.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 50 participants 328 participants 701 participants
American Indian or Alaska Native
3
   0.9%
0
   0.0%
2
   0.6%
5
   0.7%
Asian
26
   8.0%
0
   0.0%
25
   7.6%
51
   7.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.3%
0
   0.0%
4
   1.2%
5
   0.7%
White
267
  82.7%
43
  86.0%
266
  81.1%
576
  82.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
26
   8.0%
7
  14.0%
31
   9.5%
64
   9.1%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is defined as the time from date of randomization to the first documented tumor progression date or death due to any cause, whichever occurs first based on BICR assessment using RECIST v1.1. Participants who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment on or prior to initiation of subsequent anti-cancer therapy. Progressive disease (PD); 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study
Time Frame From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants of treatment A and treatment C
Arm/Group Title Treatment A Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD
Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 323 328
Median (95% Confidence Interval)
Unit of Measure: Months
16.59
(12.45 to 24.94)
8.31
(6.97 to 9.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment A over Treatment C
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.41 to 0.64
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall Survival is defined as the time between the date of randomization and the date of death due to any cause. For participants that are alive, their survival time will be censored at the date of last contact date (or "last known alive date").
Time Frame From randomization date to death date (Up to 31 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants of treatment A and treatment C
Arm/Group Title Treatment A Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD
Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 323 328
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(22.6 to NA)
[1]
Insufficient number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment A over Treatment C
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Stratified Log-Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 98.89%
0.40 to 0.89
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description

Objective Response Rate (ORR) is defined as the percentage of randomized participants who achieve a best response of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1 criteria) divided by the number of all randomized participants.

Complete response (CR): Disappearance of all target lesions. Partial response (PR): 30% decrease in the sum of diameters of target lesions.

Time Frame Up to 31 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 323 50 328
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
55.7
(50.1 to 61.2)
44.0
(30.0 to 58.7)
27.1
(22.4 to 32.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Treatment A over Treatment C
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.52
Confidence Interval (2-Sided) 95%
2.51 to 4.95
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment C
Comments [Not Specified]
Type of Statistical Test Other
Comments Treatment A - Treatment C
Method of Estimation Estimation Parameter Difference of Objective Response Rates
Estimated Value 28.6
Confidence Interval (2-Sided) 95%
21.7 to 35.6
Estimation Comments Strata adjusted difference in objective response rate (Nivolumab+Cabozantinib - Sunitinib) based on DerSimonian and Laird.
4.Secondary Outcome
Title Number of Participants Experiencing Adverse Events (AEs)
Hide Description Number of participants experiencing various types of any grade adverse events (AEs) during the specified time frame.
Time Frame From first dose to 100 days following last dose (Up to 32 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 320 50 320
Measure Type: Count of Participants
Unit of Measure: Participants
319
  99.7%
50
 100.0%
317
  99.1%
5.Secondary Outcome
Title Number of Participants Experiencing Serious Adverse Events (SAEs)
Hide Description Number of participants experiencing various types of any grade serious adverse events (SAEs) during the specified time frame.
Time Frame From first to dose to 100 days following last dose (Up to 32 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 320 50 320
Measure Type: Count of Participants
Unit of Measure: Participants
160
  50.0%
28
  56.0%
144
  45.0%
6.Secondary Outcome
Title Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Hide Description Number of participants experiencing various types of any grade adverse events (AEs) leading to discontinuation during the specified time frame.
Time Frame From first dose to 30 days following last dose (Up to 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 320 50 320
Measure Type: Count of Participants
Unit of Measure: Participants
63
  19.7%
15
  30.0%
54
  16.9%
7.Secondary Outcome
Title Number of Deaths
Hide Description Number of deaths due to any cause during the specified time frame.
Time Frame From first dose to (up to 31 months) following first dose
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 320 50 320
Measure Type: Count of Participants
Unit of Measure: Participants
67
  20.9%
14
  28.0%
99
  30.9%
8.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities
Hide Description Number of participants experiencing laboratory abnormalities in hematology, serum chemistry and electrolytes with grade 3 or higher during the specified time frame.
Time Frame From first dose to 30 days following last dose (Up to 30 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 320 50 320
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin: Any grade Number Analyzed 317 participants 49 participants 311 participants
235
  74.1%
35
  71.4%
256
  82.3%
Hemoglobin: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
9
   2.8%
5
  10.2%
15
   4.8%
Platelet Count: Any grade Number Analyzed 317 participants 49 participants 311 participants
137
  43.2%
27
  55.1%
216
  69.5%
Platelet Count: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
1
   0.3%
0
   0.0%
30
   9.6%
Leukocytes: Any grade Number Analyzed 317 participants 49 participants 311 participants
121
  38.2%
26
  53.1%
207
  66.6%
Leukocytes: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
1
   0.3%
0
   0.0%
16
   5.1%
Lymphocytes: Any grade Number Analyzed 231 participants 36 participants 231 participants
107
  46.3%
22
  61.1%
118
  51.1%
Lymphocytes: Grade 3-4 Number Analyzed 231 participants 36 participants 231 participants
16
   6.9%
4
  11.1%
24
  10.4%
Neutrophil: Any grade Number Analyzed 317 participants 49 participants 311 participants
115
  36.3%
22
  44.9%
209
  67.2%
Neutrophil: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
10
   3.2%
2
   4.1%
36
  11.6%
Alkaline Phosphatase: Any grade Number Analyzed 317 participants 49 participants 311 participants
194
  61.2%
35
  71.4%
167
  53.7%
Alkaline Phosphatase: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
12
   3.8%
6
  12.2%
6
   1.9%
Aspartate Aminotransferase (AST): Any grade Number Analyzed 317 participants 49 participants 311 participants
260
  82.0%
43
  87.8%
235
  75.6%
Aspartate Aminotransferase (AST): Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
25
   7.9%
19
  38.8%
8
   2.6%
Alanine Aminotransferase (ALT): Any grade Number Analyzed 317 participants 49 participants 311 participants
268
  84.5%
46
  93.9%
133
  42.8%
Alanine Aminotransferase (ALT): Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
31
   9.8%
24
  49.0%
11
   3.5%
Bilirubin: Any grade Number Analyzed 317 participants 49 participants 311 participants
57
  18.0%
17
  34.7%
72
  23.2%
Bilirubin: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
3
   0.9%
3
   6.1%
3
   1.0%
Creatinine: Any grade Number Analyzed 317 participants 49 participants 311 participants
221
  69.7%
34
  69.4%
211
  67.8%
Creatinine: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
4
   1.3%
0
   0.0%
2
   0.6%
Amylase: Any grade Number Analyzed 295 participants 46 participants 283 participants
48
  16.3%
28
  60.9%
41
  14.5%
Amylase: Grade 3-4 Number Analyzed 295 participants 46 participants 283 participants
30
  10.2%
10
  21.7%
17
   6.0%
Lipase: Any grade Number Analyzed 317 participants 48 participants 306 participants
36
  11.4%
27
  56.3%
42
  13.7%
Lipase: Grade 3-4 Number Analyzed 317 participants 48 participants 306 participants
46
  14.5%
20
  41.7%
41
  13.4%
Hypernatremia: Any grade Number Analyzed 317 participants 49 participants 311 participants
33
  10.4%
7
  14.3%
24
   7.7%
Hypernatremia: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyponatremia: Any grade Number Analyzed 317 participants 49 participants 311 participants
160
  50.5%
31
  63.3%
140
  45.0%
Hyponatremia: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
36
  11.4%
9
  18.4%
41
  13.2%
Hyperkalemia: Any grade Number Analyzed 317 participants 49 participants 311 participants
136
  42.9%
27
  55.1%
100
  32.2%
Hyperkalemia: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
16
   5.0%
2
   4.1%
3
   1.0%
Hypokalemia: Any grade Number Analyzed 317 participants 49 participants 311 participants
64
  20.2%
8
  16.3%
37
  11.9%
Hypokalemia: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
11
   3.5%
0
   0.0%
6
   1.9%
Hypercalcemia: Any grade Number Analyzed 315 participants 48 participants 310 participants
40
  12.7%
9
  18.8%
58
  18.7%
Hypercalcemia: Grade 3-4 Number Analyzed 315 participants 48 participants 310 participants
1
   0.3%
0
   0.0%
4
   1.3%
Hypocalcemia: Any grade Number Analyzed 315 participants 48 participants 310 participants
174
  55.2%
25
  52.1%
77
  24.8%
Hypocalcemia: Grade 3-4 Number Analyzed 315 participants 48 participants 310 participants
6
   1.9%
2
   4.2%
2
   0.6%
Hypermagnesemia: Any grade Number Analyzed 316 participants 49 participants 309 participants
42
  13.3%
9
  18.4%
29
   9.4%
Hypermagnesemia: Grade 3-4 Number Analyzed 316 participants 49 participants 309 participants
12
   3.8%
4
   8.2%
7
   2.3%
Hypomagnesemia: Any grade Number Analyzed 316 participants 49 participants 309 participants
155
  49.1%
18
  36.7%
90
  29.1%
Hypomagnesemia: Grade 3-4 Number Analyzed 316 participants 49 participants 309 participants
4
   1.3%
1
   2.0%
1
   0.3%
Hyperphosphatemia: Any grade Number Analyzed 316 participants 49 participants 309 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyperphosphatemia: Grade 3-4 Number Analyzed 316 participants 49 participants 309 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypophosphatemia: Any grade Number Analyzed 316 participants 49 participants 309 participants
226
  71.5%
34
  69.4%
154
  49.8%
Hypophosphatemia: Grade 3-4 Number Analyzed 316 participants 49 participants 309 participants
88
  27.8%
12
  24.5%
31
  10.0%
Hyperglycemia: Any grade Number Analyzed 203 participants 37 participants 196 participants
135
  66.5%
29
  78.4%
139
  70.9%
Hyperglycemia: Grade 3-4 Number Analyzed 203 participants 37 participants 196 participants
8
   3.9%
2
   5.4%
4
   2.0%
Hypoglycemia: Any grade Number Analyzed 308 participants 49 participants 295 participants
72
  23.4%
10
  20.4%
41
  13.9%
Hypoglycemia: Grade 3-4 Number Analyzed 308 participants 49 participants 295 participants
2
   0.6%
1
   2.0%
1
   0.3%
9.Secondary Outcome
Title Number of Participants With Laboratory Values Grade Shifting From Baseline
Hide Description Number of participants experiencing worsening shift from baseline in any grade and grade 3-4 of laboratory values during the specified time frame.
Time Frame From first dose to 30 days following last dose (Up to 30 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description:
Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
Overall Number of Participants Analyzed 320 50 320
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin: Any grade Number Analyzed 316 participants 49 participants 251 participants
117
  37.0%
23
  46.9%
190
  75.7%
Hemoglobin: Grade 3-4 Number Analyzed 316 participants 49 participants 251 participants
8
   2.5%
5
  10.2%
15
   6.0%
Platelet Count: Any grade Number Analyzed 316 participants 48 participants 310 participants
129
  40.8%
24
  50.0%
216
  69.7%
Platelet Count: Grade 3-4 Number Analyzed 316 participants 48 participants 310 participants
2
   0.6%
0
   0.0%
30
   9.7%
Leukocytes: Any grade Number Analyzed 316 participants 49 participants 311 participants
116
  36.7%
26
  53.1%
206
  66.2%
Leukocytes: Grade 3-4 Number Analyzed 316 participants 49 participants 311 participants
1
   0.3%
0
   0.0%
16
   5.1%
Lymphocytes: Any grade Number Analyzed 228 participants 36 participants 225 participants
95
  41.7%
20
  55.6%
102
  45.3%
Lymphocytes: Grade 3-4 Number Analyzed 228 participants 36 participants 225 participants
15
   6.6%
4
  11.1%
23
  10.2%
Neutrophil: Any grade Number Analyzed 316 participants 49 participants 311 participants
112
  35.4%
22
  44.9%
209
  67.2%
Neutrophil: Grade 3-4 Number Analyzed 316 participants 49 participants 311 participants
10
   3.2%
2
   4.1%
36
  11.6%
Alkaline Phosphatase: Any grade Number Analyzed 317 participants 49 participants 310 participants
131
  41.3%
31
  63.3%
115
  37.1%
Alkaline Phosphatase: Grade 3-4 Number Analyzed 317 participants 49 participants 310 participants
9
   2.8%
6
  12.2%
5
   1.6%
Aspartate Aminotransferase (AST): Any grade Number Analyzed 317 participants 49 participants 310 participants
245
  77.3%
42
  85.7%
177
  57.1%
Aspartate Aminotransferase (AST): Grade 3-4 Number Analyzed 317 participants 49 participants 310 participants
25
   7.9%
19
  38.8%
8
   2.6%
Alanine Aminotransferase (ALT): Any grade Number Analyzed 316 participants 49 participants 310 participants
249
  78.8%
43
  87.8%
121
  39.0%
Alanine Aminotransferase (ALT) Grade 3-4 Number Analyzed 316 participants 49 participants 310 participants
31
   9.8%
24
  49.0%
11
   3.5%
Bilirubin: Any grade Number Analyzed 316 participants 49 participants 309 participants
55
  17.4%
17
  34.7%
68
  22.0%
Bilirubin: Grade 3-4 Number Analyzed 316 participants 49 participants 309 participants
3
   0.9%
3
   6.1%
3
   1.0%
Creatinine: Any grade Number Analyzed 317 participants 49 participants 311 participants
123
  38.8%
22
  44.9%
132
  42.4%
Creatinine: Grade 3-4 Number Analyzed 317 participants 49 participants 311 participants
4
   1.3%
0
   0.0%
2
   0.6%
Amylase: Any grade Number Analyzed 285 participants 46 participants 277 participants
117
  41.1%
26
  56.5%
77
  27.8%
Amylase: Grade 3-4 Number Analyzed 285 participants 46 participants 277 participants
28
   9.8%
10
  21.7%
16
   5.8%
Lipase: Any grade Number Analyzed 308 participants 47 participants 300 participants
127
  41.2%
27
  57.4%
114
  38.0%
Lipase: Grade 3-4 Number Analyzed 308 participants 47 participants 300 participants
42
  13.6%
20
  42.6%
40
  13.3%
Hypernatremia: Any grade Number Analyzed 317 participants 49 participants 310 participants
33
  10.4%
7
  14.3%
24
   7.7%
Hypernatremia: Grade 3-4 Number Analyzed 317 participants 49 participants 310 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyponatremia: Any grade Number Analyzed 317 participants 49 participants 310 participants
136
  42.9%
30
  61.2%
111
  35.8%
Hyponatremia: Grade 3-4 Number Analyzed 317 participants 49 participants 310 participants
34
  10.7%
8
  16.3%
37
  11.9%
Hyperkalemia: Any grade Number Analyzed 317 participants 49 participants 309 participants
111
  35.0%
25
  51.0%
82
  26.5%
Hyperkalemia: Grade 3-4 Number Analyzed 317 participants 49 participants 309 participants
15
   4.7%
2
   4.1%
3
   1.0%
Hypokalemia: Any grade Number Analyzed 317 participants 49 participants 309 participants
61
  19.2%
8
  16.3%
35
  11.3%
Hypokalemia: Grade 3-4 Number Analyzed 317 participants 49 participants 309 participants
10
   3.2%
0
   0.0%
5
   1.6%
Hypercalcemia: Any grade Number Analyzed 314 participants 48 participants 309 participants
30
   9.6%
7
  14.6%
46
  14.9%
Hypercalcemia: Grade 3-4 Number Analyzed 314 participants 48 participants 309 participants
1
   0.3%
0
   0.0%
3
   1.0%
Hypocalcemia: Any grade Number Analyzed 314 participants 48 participants 309 participants
170
  54.1%
25
  52.1%
73
  23.6%
Hypocalcemia: Grade 3-4 Number Analyzed 314 participants 48 participants 309 participants
6
   1.9%
2
   4.2%
2
   0.6%
Hypermagnesemia: Any grade Number Analyzed 308 participants 49 participants 304 participants
38
  12.3%
9
  18.4%
26
   8.6%
Hypermagnesemia: Grade 3-4 Number Analyzed 308 participants 49 participants 304 participants
12
   3.9%
4
   8.2%
7
   2.3%
Hypomagnesemia: Any grade Number Analyzed 308 participants 49 participants 304 participants
146
  47.4%
16
  32.7%
77
  25.3%
Hypomagnesemia: Grade 3-4 Number Analyzed 308 participants 49 participants 304 participants
4
   1.3%
1
   2.0%
1
   0.3%
Hyperphosphatemia: Any grade Number Analyzed 307 participants 49 participants 307 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hyperphosphatemia: Grade 3-4 Number Analyzed 307 participants 49 participants 307 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hypophosphatemia: Any grade Number Analyzed 307 participants 49 participants 307 participants
211
  68.7%
33
  67.3%
147
  47.9%
Hypophosphatemia: Grade 3-4 Number Analyzed 307 participants 49 participants 307 participants
85
  27.7%
12
  24.5%
31
  10.1%
Hyperglycemia: Any grade Number Analyzed 170 participants 33 participants 173 participants
74
  43.5%
17
  51.5%
76
  43.9%
Hyperglycemia: Grade 3-4 Number Analyzed 170 participants 33 participants 173 participants
6
   3.5%
2
   6.1%
3
   1.7%
Hypoglycemia: Any grade Number Analyzed 262 participants 45 participants 270 participants
67
  25.6%
9
  20.0%
37
  13.7%
Hypoglycemia: Grade 3-4 Number Analyzed 262 participants 45 participants 270 participants
2
   0.8%
1
   2.2%
1
   0.4%
Time Frame All cause mortality: From first visit to up to 31 months following first visit SAEs and AEs: From first dose to 100 days following last dose (up to 32 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment A Treatment B Treatment C
Hide Arm/Group Description Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Nivolumab 3 mg/kg IV Q3W (x4 doses) + Cabozantinib 40 mg PO QD + Ipilimumab 1 mg/kg IV Q3W (x4 doses)

Then

Nivolumab 240 mg flat dose IV Q2W + Cabozantinib 40 mg PO QD

Sunitinib 50 mg PO QD for 4 weeks, followed by 2 weeks off, per cycle
All-Cause Mortality
Treatment A Treatment B Treatment C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   67/320 (20.94%)   14/50 (28.00%)   99/320 (30.94%) 
Hide Serious Adverse Events
Treatment A Treatment B Treatment C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   160/320 (50.00%)   28/50 (56.00%)   144/320 (45.00%) 
Blood and lymphatic system disorders       
Anaemia  1  2/320 (0.63%)  1/50 (2.00%)  11/320 (3.44%) 
Disseminated intravascular coagulation  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Febrile neutropenia  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Pancytopenia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Thrombocytopenia  1  0/320 (0.00%)  1/50 (2.00%)  3/320 (0.94%) 
Cardiac disorders       
Acute myocardial infarction  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Atrial fibrillation  1  3/320 (0.94%)  0/50 (0.00%)  0/320 (0.00%) 
Atrial tachycardia  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Atrioventricular block complete  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Bradycardia  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Cardiac arrest  1  3/320 (0.94%)  0/50 (0.00%)  0/320 (0.00%) 
Cardiac failure  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Cardiac failure acute  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Cardiac failure congestive  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Cardio-respiratory arrest  1  2/320 (0.63%)  0/50 (0.00%)  2/320 (0.63%) 
Intracardiac thrombus  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Myocardial infarction  1  2/320 (0.63%)  1/50 (2.00%)  1/320 (0.31%) 
Myocardial ischaemia  1  1/320 (0.31%)  0/50 (0.00%)  2/320 (0.63%) 
Myocarditis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Endocrine disorders       
Adrenal haemorrhage  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Adrenal insufficiency  1  6/320 (1.88%)  2/50 (4.00%)  0/320 (0.00%) 
Adrenocorticotropic hormone deficiency  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Hyperthyroidism  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Hypophysitis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Hypothalamo-pituitary disorder  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Hypothyroidism  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Thyroiditis acute  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Eye disorders       
Vision blurred  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Gastrointestinal disorders       
Abdominal distension  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Abdominal hernia  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Abdominal pain  1  3/320 (0.94%)  0/50 (0.00%)  4/320 (1.25%) 
Anal fistula  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Colitis  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Colitis microscopic  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Colonic fistula  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Constipation  1  0/320 (0.00%)  1/50 (2.00%)  1/320 (0.31%) 
Diarrhoea  1  15/320 (4.69%)  0/50 (0.00%)  0/320 (0.00%) 
Dysphagia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Enteritis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Epigastric discomfort  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Gastric haemorrhage  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Gastrointestinal haemorrhage  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Inguinal hernia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Intestinal obstruction  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Intestinal perforation  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Intussusception  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Large intestinal haemorrhage  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Large intestine perforation  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Lower gastrointestinal haemorrhage  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Nausea  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Obstruction gastric  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Oesophagitis  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Pancreatitis  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Pancreatitis acute  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Retroperitoneal haematoma  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Small intestinal obstruction  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Small intestinal perforation  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Stomatitis  1  3/320 (0.94%)  0/50 (0.00%)  0/320 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/320 (0.31%)  0/50 (0.00%)  2/320 (0.63%) 
Vomiting  1  5/320 (1.56%)  0/50 (0.00%)  2/320 (0.63%) 
General disorders       
Asthenia  1  2/320 (0.63%)  1/50 (2.00%)  2/320 (0.63%) 
Chills  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Condition aggravated  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Death  1  1/320 (0.31%)  1/50 (2.00%)  2/320 (0.63%) 
Face oedema  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Fatigue  1  2/320 (0.63%)  0/50 (0.00%)  1/320 (0.31%) 
General physical health deterioration  1  2/320 (0.63%)  1/50 (2.00%)  1/320 (0.31%) 
Hernia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Inflammation  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Malaise  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Mucosal inflammation  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Necrosis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Pain  1  2/320 (0.63%)  0/50 (0.00%)  6/320 (1.88%) 
Pyrexia  1  4/320 (1.25%)  0/50 (0.00%)  5/320 (1.56%) 
Sudden death  1  1/320 (0.31%)  0/50 (0.00%)  2/320 (0.63%) 
Hepatobiliary disorders       
Autoimmune hepatitis  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Bile duct stone  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Cholangitis  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Cholecystitis  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Cholecystitis acute  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Cholestasis  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Drug-induced liver injury  1  0/320 (0.00%)  1/50 (2.00%)  1/320 (0.31%) 
Hepatic cirrhosis  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Hepatic failure  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Hepatic function abnormal  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Hepatitis  1  2/320 (0.63%)  2/50 (4.00%)  0/320 (0.00%) 
Hepatotoxicity  1  2/320 (0.63%)  1/50 (2.00%)  1/320 (0.31%) 
Hyperbilirubinaemia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Immune-mediated hepatitis  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Jaundice  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Portal vein thrombosis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Immune system disorders       
Anaphylactic reaction  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Infections and infestations       
Abdominal sepsis  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Appendicitis perforated  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Bronchitis pneumococcal  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Campylobacter infection  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Cellulitis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Clostridium difficile colitis  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Clostridium difficile infection  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Cystitis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Dengue fever  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Diverticulitis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Encephalitis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Febrile infection  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Gastroenteritis viral  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Haematoma infection  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Herpes zoster  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Infection  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Infectious pleural effusion  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Large intestine infection  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Lower respiratory tract infection  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Lung abscess  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Otitis externa  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Pneumocystis jirovecii infection  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Pneumonia  1  9/320 (2.81%)  4/50 (8.00%)  8/320 (2.50%) 
Pneumonia necrotising  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Pulmonary sepsis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Pyelonephritis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Respiratory tract infection  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Sepsis  1  4/320 (1.25%)  0/50 (0.00%)  0/320 (0.00%) 
Septic shock  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Soft tissue infection  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Tuberculosis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Upper respiratory tract infection  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Urinary tract infection  1  7/320 (2.19%)  0/50 (0.00%)  5/320 (1.56%) 
Injury, poisoning and procedural complications       
Clavicle fracture  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Compression fracture  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Fall  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Femur fracture  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Infusion related reaction  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Lumbar vertebral fracture  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Overdose  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Radiation injury  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Spinal compression fracture  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Spinal fracture  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Toxicity to various agents  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Investigations       
Alanine aminotransferase increased  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Aspartate aminotransferase increased  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Bordetella test positive  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Ejection fraction decreased  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Escherichia test positive  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Hepatic enzyme increased  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Human rhinovirus test positive  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Influenza A virus test positive  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Liver function test abnormal  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Platelet count decreased  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Transaminases increased  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Metabolism and nutrition disorders       
Decreased appetite  1  0/320 (0.00%)  0/50 (0.00%)  3/320 (0.94%) 
Dehydration  1  3/320 (0.94%)  0/50 (0.00%)  2/320 (0.63%) 
Electrolyte imbalance  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Hypercalcaemia  1  0/320 (0.00%)  0/50 (0.00%)  4/320 (1.25%) 
Hyperglycaemia  1  2/320 (0.63%)  1/50 (2.00%)  3/320 (0.94%) 
Hyperkalaemia  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Hypoglycaemia  1  2/320 (0.63%)  0/50 (0.00%)  1/320 (0.31%) 
Hyponatraemia  1  7/320 (2.19%)  1/50 (2.00%)  5/320 (1.56%) 
Metabolic disorder  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Arthritis  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Back pain  1  3/320 (0.94%)  0/50 (0.00%)  4/320 (1.25%) 
Bone lesion  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Bone pain  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Flank pain  1  0/320 (0.00%)  0/50 (0.00%)  3/320 (0.94%) 
Intervertebral disc protrusion  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Limb discomfort  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Lumbar spinal stenosis  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Muscular weakness  1  1/320 (0.31%)  0/50 (0.00%)  2/320 (0.63%) 
Musculoskeletal chest pain  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Neck pain  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Osteoarthritis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Osteolysis  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Pain in extremity  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Pathological fracture  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Polyarthritis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Trismus  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Bladder neoplasm  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Bowen's disease  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Cancer pain  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Clear cell renal cell carcinoma  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Intracranial tumour haemorrhage  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Malignant neoplasm progression  1  24/320 (7.50%)  4/50 (8.00%)  23/320 (7.19%) 
Metastases to bone  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Metastases to central nervous system  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Metastases to spine  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Neoplasm progression  1  2/320 (0.63%)  0/50 (0.00%)  4/320 (1.25%) 
Renal cancer  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Renal cancer recurrent  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Squamous cell carcinoma  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Tumour associated fever  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Tumour pain  1  3/320 (0.94%)  0/50 (0.00%)  1/320 (0.31%) 
Nervous system disorders       
Altered state of consciousness  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Aphasia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Central nervous system lesion  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Cerebral haemorrhage  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Cerebral ischaemia  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Dizziness  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Encephalopathy  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Guillain-Barre syndrome  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Haemorrhage intracranial  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Headache  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Hydrocephalus  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Ischaemic stroke  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Lethargy  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Peripheral sensorimotor neuropathy  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Presyncope  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Sciatica  1  1/320 (0.31%)  0/50 (0.00%)  2/320 (0.63%) 
Seizure  1  2/320 (0.63%)  0/50 (0.00%)  2/320 (0.63%) 
Syncope  1  2/320 (0.63%)  2/50 (4.00%)  1/320 (0.31%) 
Psychiatric disorders       
Confusional state  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Delirium  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Renal and urinary disorders       
Acute kidney injury  1  2/320 (0.63%)  0/50 (0.00%)  6/320 (1.88%) 
Azotaemia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Bladder tamponade  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Haematuria  1  0/320 (0.00%)  0/50 (0.00%)  3/320 (0.94%) 
Nephritis  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Proteinuria  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Renal colic  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Renal failure  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Urinary retention  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Ovarian cyst  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Prostatitis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  0/320 (0.00%)  0/50 (0.00%)  2/320 (0.63%) 
Asthma  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Chronic obstructive pulmonary disease  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Cough  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Dyspnoea  1  3/320 (0.94%)  1/50 (2.00%)  3/320 (0.94%) 
Haemoptysis  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Hypoxia  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Mediastinal haemorrhage  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Oropharyngeal pain  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Pleural effusion  1  2/320 (0.63%)  0/50 (0.00%)  9/320 (2.81%) 
Pneumonitis  1  9/320 (2.81%)  0/50 (0.00%)  1/320 (0.31%) 
Pulmonary artery thrombosis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Pulmonary embolism  1  9/320 (2.81%)  0/50 (0.00%)  3/320 (0.94%) 
Respiratory distress  1  0/320 (0.00%)  0/50 (0.00%)  1/320 (0.31%) 
Respiratory failure  1  1/320 (0.31%)  0/50 (0.00%)  9/320 (2.81%) 
Skin and subcutaneous tissue disorders       
Dermatitis  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Peau d'orange  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Pemphigoid  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Rash  1  1/320 (0.31%)  1/50 (2.00%)  0/320 (0.00%) 
Rash erythematous  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Rash papular  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Skin exfoliation  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Skin ulcer  1  2/320 (0.63%)  0/50 (0.00%)  0/320 (0.00%) 
Surgical and medical procedures       
Central venous catheterisation  1  0/320 (0.00%)  1/50 (2.00%)  0/320 (0.00%) 
Surgery  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Vascular disorders       
Arterial thrombosis  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Bleeding varicose vein  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Deep vein thrombosis  1  3/320 (0.94%)  0/50 (0.00%)  1/320 (0.31%) 
Embolism  1  2/320 (0.63%)  0/50 (0.00%)  1/320 (0.31%) 
Hypertension  1  3/320 (0.94%)  0/50 (0.00%)  1/320 (0.31%) 
Hypotension  1  1/320 (0.31%)  1/50 (2.00%)  3/320 (0.94%) 
Peripheral ischaemia  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Thrombosis  1  1/320 (0.31%)  0/50 (0.00%)  1/320 (0.31%) 
Vascular occlusion  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
Venous thrombosis limb  1  1/320 (0.31%)  0/50 (0.00%)  0/320 (0.00%) 
1
Term from vocabulary, 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment A Treatment B Treatment C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   316/320 (98.75%)   48/50 (96.00%)   306/320 (95.63%) 
Blood and lymphatic system disorders       
Anaemia  1  48/320 (15.00%)  8/50 (16.00%)  85/320 (26.56%) 
Leukopenia  1  7/320 (2.19%)  0/50 (0.00%)  24/320 (7.50%) 
Neutropenia  1  15/320 (4.69%)  4/50 (8.00%)  50/320 (15.63%) 
Thrombocytopenia  1  25/320 (7.81%)  3/50 (6.00%)  62/320 (19.38%) 
Endocrine disorders       
Hyperthyroidism  1  31/320 (9.69%)  3/50 (6.00%)  9/320 (2.81%) 
Hypothyroidism  1  109/320 (34.06%)  15/50 (30.00%)  95/320 (29.69%) 
Gastrointestinal disorders       
Abdominal distension  1  5/320 (1.56%)  3/50 (6.00%)  7/320 (2.19%) 
Abdominal pain  1  50/320 (15.63%)  9/50 (18.00%)  25/320 (7.81%) 
Abdominal pain upper  1  22/320 (6.88%)  6/50 (12.00%)  21/320 (6.56%) 
Colitis  1  6/320 (1.88%)  4/50 (8.00%)  1/320 (0.31%) 
Constipation  1  39/320 (12.19%)  12/50 (24.00%)  41/320 (12.81%) 
Diarrhoea  1  202/320 (63.13%)  28/50 (56.00%)  151/320 (47.19%) 
Dry mouth  1  21/320 (6.56%)  3/50 (6.00%)  12/320 (3.75%) 
Dyspepsia  1  26/320 (8.13%)  4/50 (8.00%)  40/320 (12.50%) 
Gastritis  1  9/320 (2.81%)  4/50 (8.00%)  7/320 (2.19%) 
Gastrooesophageal reflux disease  1  25/320 (7.81%)  4/50 (8.00%)  36/320 (11.25%) 
Nausea  1  86/320 (26.88%)  15/50 (30.00%)  99/320 (30.94%) 
Oral dysaesthesia  1  2/320 (0.63%)  3/50 (6.00%)  0/320 (0.00%) 
Stomatitis  1  54/320 (16.88%)  8/50 (16.00%)  82/320 (25.62%) 
Vomiting  1  53/320 (16.56%)  10/50 (20.00%)  66/320 (20.63%) 
General disorders       
Asthenia  1  71/320 (22.19%)  13/50 (26.00%)  58/320 (18.13%) 
Chest pain  1  8/320 (2.50%)  3/50 (6.00%)  8/320 (2.50%) 
Fatigue  1  102/320 (31.87%)  19/50 (38.00%)  112/320 (35.00%) 
Malaise  1  12/320 (3.75%)  2/50 (4.00%)  17/320 (5.31%) 
Mucosal inflammation  1  66/320 (20.63%)  13/50 (26.00%)  80/320 (25.00%) 
Oedema peripheral  1  35/320 (10.94%)  8/50 (16.00%)  28/320 (8.75%) 
Pain  1  16/320 (5.00%)  4/50 (8.00%)  17/320 (5.31%) 
Pyrexia  1  38/320 (11.88%)  12/50 (24.00%)  25/320 (7.81%) 
Hepatobiliary disorders       
Hepatotoxicity  1  16/320 (5.00%)  10/50 (20.00%)  12/320 (3.75%) 
Immune system disorders       
Hypersensitivity  1  4/320 (1.25%)  3/50 (6.00%)  4/320 (1.25%) 
Infections and infestations       
Bronchitis  1  9/320 (2.81%)  3/50 (6.00%)  7/320 (2.19%) 
Nasopharyngitis  1  22/320 (6.88%)  5/50 (10.00%)  14/320 (4.38%) 
Upper respiratory tract infection  1  35/320 (10.94%)  5/50 (10.00%)  12/320 (3.75%) 
Urinary tract infection  1  23/320 (7.19%)  9/50 (18.00%)  17/320 (5.31%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  3/320 (0.94%)  3/50 (6.00%)  1/320 (0.31%) 
Investigations       
Alanine aminotransferase increased  1  90/320 (28.13%)  21/50 (42.00%)  28/320 (8.75%) 
Amylase increased  1  48/320 (15.00%)  8/50 (16.00%)  29/320 (9.06%) 
Aspartate aminotransferase increased  1  82/320 (25.62%)  16/50 (32.00%)  36/320 (11.25%) 
Blood alkaline phosphatase increased  1  37/320 (11.56%)  8/50 (16.00%)  27/320 (8.44%) 
Blood bilirubin increased  1  18/320 (5.63%)  6/50 (12.00%)  13/320 (4.06%) 
Blood cholesterol increased  1  7/320 (2.19%)  4/50 (8.00%)  10/320 (3.13%) 
Blood creatinine increased  1  43/320 (13.44%)  7/50 (14.00%)  43/320 (13.44%) 
Blood sodium decreased  1  6/320 (1.88%)  3/50 (6.00%)  2/320 (0.63%) 
Blood thyroid stimulating hormone decreased  1  1/320 (0.31%)  5/50 (10.00%)  2/320 (0.63%) 
Blood thyroid stimulating hormone increased  1  27/320 (8.44%)  3/50 (6.00%)  20/320 (6.25%) 
Lipase increased  1  54/320 (16.88%)  13/50 (26.00%)  38/320 (11.88%) 
Lymphocyte count decreased  1  6/320 (1.88%)  3/50 (6.00%)  10/320 (3.13%) 
Neutrophil count decreased  1  12/320 (3.75%)  2/50 (4.00%)  27/320 (8.44%) 
Platelet count decreased  1  18/320 (5.63%)  6/50 (12.00%)  60/320 (18.75%) 
Transaminases increased  1  12/320 (3.75%)  4/50 (8.00%)  5/320 (1.56%) 
Weight decreased  1  36/320 (11.25%)  8/50 (16.00%)  10/320 (3.13%) 
White blood cell count decreased  1  7/320 (2.19%)  4/50 (8.00%)  18/320 (5.63%) 
Metabolism and nutrition disorders       
Decreased appetite  1  92/320 (28.75%)  15/50 (30.00%)  66/320 (20.63%) 
Hyperglycaemia  1  28/320 (8.75%)  3/50 (6.00%)  14/320 (4.38%) 
Hyperkalaemia  1  21/320 (6.56%)  4/50 (8.00%)  6/320 (1.88%) 
Hypoalbuminaemia  1  18/320 (5.63%)  4/50 (8.00%)  12/320 (3.75%) 
Hypocalcaemia  1  22/320 (6.88%)  4/50 (8.00%)  7/320 (2.19%) 
Hypoglycaemia  1  4/320 (1.25%)  3/50 (6.00%)  5/320 (1.56%) 
Hypokalaemia  1  18/320 (5.63%)  2/50 (4.00%)  11/320 (3.44%) 
Hypomagnesaemia  1  44/320 (13.75%)  3/50 (6.00%)  15/320 (4.69%) 
Hyponatraemia  1  48/320 (15.00%)  8/50 (16.00%)  28/320 (8.75%) 
Hypophosphataemia  1  46/320 (14.37%)  6/50 (12.00%)  18/320 (5.63%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  59/320 (18.44%)  7/50 (14.00%)  29/320 (9.06%) 
Back pain  1  56/320 (17.50%)  11/50 (22.00%)  38/320 (11.88%) 
Muscle spasms  1  38/320 (11.88%)  7/50 (14.00%)  5/320 (1.56%) 
Musculoskeletal pain  1  17/320 (5.31%)  3/50 (6.00%)  10/320 (3.13%) 
Musculoskeletal stiffness  1  1/320 (0.31%)  3/50 (6.00%)  2/320 (0.63%) 
Myalgia  1  16/320 (5.00%)  11/50 (22.00%)  23/320 (7.19%) 
Pain in extremity  1  30/320 (9.38%)  6/50 (12.00%)  29/320 (9.06%) 
Nervous system disorders       
Dizziness  1  32/320 (10.00%)  9/50 (18.00%)  19/320 (5.94%) 
Dysgeusia  1  76/320 (23.75%)  9/50 (18.00%)  70/320 (21.88%) 
Headache  1  50/320 (15.63%)  9/50 (18.00%)  36/320 (11.25%) 
Paraesthesia  1  11/320 (3.44%)  3/50 (6.00%)  8/320 (2.50%) 
Psychiatric disorders       
Anxiety  1  8/320 (2.50%)  4/50 (8.00%)  9/320 (2.81%) 
Depression  1  15/320 (4.69%)  3/50 (6.00%)  9/320 (2.81%) 
Insomnia  1  27/320 (8.44%)  6/50 (12.00%)  17/320 (5.31%) 
Renal and urinary disorders       
Proteinuria  1  33/320 (10.31%)  2/50 (4.00%)  25/320 (7.81%) 
Renal failure  1  10/320 (3.13%)  3/50 (6.00%)  4/320 (1.25%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  58/320 (18.13%)  14/50 (28.00%)  51/320 (15.94%) 
Dysphonia  1  56/320 (17.50%)  7/50 (14.00%)  11/320 (3.44%) 
Dyspnoea  1  30/320 (9.38%)  6/50 (12.00%)  27/320 (8.44%) 
Epistaxis  1  22/320 (6.88%)  2/50 (4.00%)  32/320 (10.00%) 
Oropharyngeal pain  1  30/320 (9.38%)  5/50 (10.00%)  11/320 (3.44%) 
Pulmonary embolism  1  12/320 (3.75%)  3/50 (6.00%)  3/320 (0.94%) 
Rhinorrhoea  1  12/320 (3.75%)  3/50 (6.00%)  3/320 (0.94%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  17/320 (5.31%)  3/50 (6.00%)  6/320 (1.88%) 
Dry skin  1  21/320 (6.56%)  2/50 (4.00%)  15/320 (4.69%) 
Palmar-plantar erythrodysaesthesia syndrome  1  128/320 (40.00%)  20/50 (40.00%)  130/320 (40.63%) 
Pruritus  1  60/320 (18.75%)  11/50 (22.00%)  15/320 (4.69%) 
Rash  1  69/320 (21.56%)  15/50 (30.00%)  26/320 (8.13%) 
Rash maculo-papular  1  27/320 (8.44%)  5/50 (10.00%)  6/320 (1.88%) 
Yellow skin  1  0/320 (0.00%)  1/50 (2.00%)  22/320 (6.88%) 
Vascular disorders       
Hypertension  1  112/320 (35.00%)  18/50 (36.00%)  121/320 (37.81%) 
Hypotension  1  13/320 (4.06%)  4/50 (8.00%)  3/320 (0.94%) 
1
Term from vocabulary, 22.1
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
Layout table for Results Point of Contact information
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):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03141177    
Other Study ID Numbers: CA209-9ER
2017-000759-20 ( EudraCT Number )
First Submitted: May 3, 2017
First Posted: May 4, 2017
Results First Submitted: February 11, 2022
Results First Posted: April 26, 2022
Last Update Posted: September 16, 2022