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A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer (CHECKMATE 920)

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: NCT02982954
Recruitment Status : Completed
First Posted : December 6, 2016
Results First Posted : October 14, 2021
Last Update Posted : November 1, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Cell Carcinoma
Interventions Drug: Nivolumab
Drug: Ipilimumab
Enrollment 211
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Period Title: Overall Study
Started 106 52 28 25
Completed 0 0 0 0
Not Completed 106 52 28 25
Reason Not Completed
Death             55             29             15             20
Lost to Follow-up             2             1             0             0
Participant withdrew consent             7             5             1             1
Other reasons             42             17             12             3
Premature site closure             0             0             0             1
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Total
Hide Arm/Group Description Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses Total of all reporting groups
Overall Number of Baseline Participants 106 52 28 25 211
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 52 participants 28 participants 25 participants 211 participants
62.8  (9.43) 60.1  (14.09) 61.3  (11.06) 65.2  (12.54) 62.2  (11.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 52 participants 28 participants 25 participants 211 participants
Female
20
  18.9%
16
  30.8%
4
  14.3%
6
  24.0%
46
  21.8%
Male
86
  81.1%
36
  69.2%
24
  85.7%
19
  76.0%
165
  78.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 52 participants 28 participants 25 participants 211 participants
Hispanic or Latino
5
   4.7%
3
   5.8%
1
   3.6%
1
   4.0%
10
   4.7%
Not Hispanic or Latino
101
  95.3%
48
  92.3%
27
  96.4%
24
  96.0%
200
  94.8%
Unknown or Not Reported
0
   0.0%
1
   1.9%
0
   0.0%
0
   0.0%
1
   0.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 52 participants 28 participants 25 participants 211 participants
American Indian or Alaska Native
0
   0.0%
1
   1.9%
0
   0.0%
0
   0.0%
1
   0.5%
Asian
0
   0.0%
1
   1.9%
1
   3.6%
0
   0.0%
2
   0.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.9%
6
  11.5%
1
   3.6%
1
   4.0%
9
   4.3%
White
104
  98.1%
40
  76.9%
26
  92.9%
24
  96.0%
194
  91.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.9%
4
   7.7%
0
   0.0%
0
   0.0%
5
   2.4%
1.Primary Outcome
Title Number of Participants With High Grade (Grade 3-4) Immune Mediated Adverse Events (IMAEs)
Hide Description Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity
Time Frame Approximately 39 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Measure Type: Count of Participants
Unit of Measure: Participants
Pneumonitis
1
   0.9%
0
   0.0%
0
   0.0%
0
   0.0%
Diarrhoea/Colitis
8
   7.5%
4
   7.7%
2
   7.1%
0
   0.0%
Hepatitis
3
   2.8%
1
   1.9%
1
   3.6%
1
   4.0%
Nephritis and Renal Dysfunction
0
   0.0%
2
   3.8%
0
   0.0%
0
   0.0%
Rash
7
   6.6%
3
   5.8%
1
   3.6%
0
   0.0%
Hypersensitivity
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Adrenal Insufficiency
3
   2.8%
1
   1.9%
0
   0.0%
1
   4.0%
Hypothyroidism and Thyroiditis
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
Diabetes Mellitus
3
   2.8%
0
   0.0%
1
   3.6%
0
   0.0%
Hyperthyroidism
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hypophysitis
0
   0.0%
1
   1.9%
1
   3.6%
0
   0.0%
2.Primary Outcome
Title Number of Participants With High Grade (Grade 5) Immune Mediated Adverse Events (IMAEs)
Hide Description Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity
Time Frame Approximately 39 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Measure Type: Count of Participants
Unit of Measure: Participants
Pneumonitis
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Diarrhoea/Colitis
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hepatitis
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Nephritis and Renal Dysfunction
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Rash
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hypersensitivity
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Adrenal Insufficiency
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hypothyroidism and Thyroiditis
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Diabetes Mellitus
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hyperthyroidism
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hypophysitis
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Secondary Outcome
Title Time to Onset of Grade 3-5 Immune Mediated Adverse Events (IMAEs)
Hide Description Time to onset is defined as the duration of time in weeks from the first dosing to the immune modulating adverse event onset date. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time Frame From first dose to the earliest IMAE (grade 3-5) event onset date (up to approximately 116 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants Who Experienced at Least 1 IMAE Where Immune-modulating Medication was Initiated
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Median (Full Range)
Unit of Measure: Weeks
Pneumonitis Number Analyzed 1 participants 0 participants 0 participants 0 participants
12.7
(12.7 to 12.7)
Diarrhoea/Colitis Number Analyzed 8 participants 4 participants 2 participants 0 participants
21.79
(1.7 to 115.7)
10.43
(4.4 to 20.1)
11.0
(10.1 to 11.9)
Hepatitis Number Analyzed 3 participants 1 participants 1 participants 1 participants
8.43
(2.0 to 82.1)
9.4
(9.4 to 9.4)
11.6
(11.6 to 11.6)
10.1
(10.1 to 10.1)
Nephritis and Renal Dysfunction Number Analyzed 0 participants 2 participants 0 participants 0 participants
9.43
(1.4 to 17.4)
Rash Number Analyzed 7 participants 3 participants 1 participants 0 participants
4.00
(1.1 to 80.4)
6.14
(2.3 to 13.7)
8.3
(8.3 to 8.3)
Hypersensitivity Number Analyzed 0 participants 0 participants 0 participants 0 participants
Immune Mediated Arthritis Number Analyzed 0 participants 1 participants 0 participants 0 participants
38.9
(38.9 to 38.9)
Myositis/Rhabdomyolysis Event Number Analyzed 0 participants 0 participants 0 participants 0 participants
Adrenal Insufficiency Number Analyzed 2 participants 1 participants 0 participants 1 participants
36.21
(21.0 to 51.4)
12.7
(12.7 to 12.7)
14.9
(14.9 to 14.9)
Hypothyroidism and Thyroiditis Number Analyzed 0 participants 0 participants 0 participants 0 participants
Diabetes Mellitus Number Analyzed 0 participants 0 participants 1 participants 0 participants
2.0
(2.0 to 2.0)
Hyperthyroidism Number Analyzed 0 participants 0 participants 0 participants 0 participants
Hypophysitis Number Analyzed 0 participants 1 participants 0 participants 0 participants
18.7
(18.7 to 18.7)
4.Secondary Outcome
Title Time to Resolution of Grade 3-5 Immune Mediated Adverse Events (IMAEs)
Hide Description Time to resolution is defined as the longest time from IMAE onset date to complete resolution or improvement to the grade at baseline experienced by the participant (the IMAE end date). Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time Frame From the IMAE onset date to the IMAE end date, up to approximately 194 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants Who Experienced at Least 1 IMAE Where Immune-modulating Medication was Initiated
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Median (Full Range)
Unit of Measure: Weeks
Pneumonitis Number Analyzed 1 participants 0 participants 0 participants 0 participants
0.9
(0.9 to 0.9)
Diarrhoea/Colitis Number Analyzed 9 participants 4 participants 3 participants 0 participants
2.71
(0.7 to 193.9)
5.93
(0.9 to 16.9)
1.14
(1.1 to 4.9)
Hepatitis Number Analyzed 3 participants 2 participants 1 participants 1 participants
NA [1] 
(7.9 to 144.9)
NA [1] 
(14.9 to 18.3)
3.00
(3.0 to 3.0)
2.1
(2.1 to 2.1)
Nephritis and Renal Dysfunction Number Analyzed 0 participants 2 participants 0 participants 0 participants
7.79
(1.1 to 14.4)
Rash Number Analyzed 7 participants 3 participants 1 participants 0 participants
26.86
(5.3 to 181.6)
8.00
(3.1 to 69.9)
5.3
(5.3 to 5.3)
Hypersensitivity Number Analyzed 0 participants 0 participants 0 participants 0 participants
Adrenal Insufficiency Number Analyzed 2 participants 0 participants 0 participants 1 participants
NA [1] 
(0.4 to 170.0)
6.0
(6.0 to 6.0)
Diabetes Mellitus Number Analyzed 0 participants 0 participants 1 participants 0 participants
1.1
(1.1 to 1.1)
Hypophysitis Number Analyzed 0 participants 1 participants 0 participants 0 participants
7.6
(7.6 to 7.6)
Immune Mediated Arthritis Number Analyzed 0 participants 1 participants 0 participants 0 participants
37.0
(37.0 to 37.0)
[1]
Median not calculated due to insufficient number of events.
5.Secondary Outcome
Title Number of Participants Who Received Immune Modulating Medication for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs)
Hide Description The number of participants who received immune modulating medication for participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time Frame From first dose up to 100 days post last dose (up to approximately 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Measure Type: Count of Participants
Unit of Measure: Participants
Pneumonitis Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
 0 0 0
Diarrhoea/Colitis Number Analyzed 8 participants 4 participants 2 participants 0 participants
8
 100.0%
4
 100.0%
2
 100.0%
 0
Hepatitis Number Analyzed 3 participants 1 participants 1 participants 1 participants
3
 100.0%
1
 100.0%
1
 100.0%
1
 100.0%
Nephritis and Renal Dysfunction Number Analyzed 0 participants 2 participants 0 participants 0 participants
0
2
 100.0%
 0 0
Rash Number Analyzed 7 participants 3 participants 1 participants 0 participants
7
 100.0%
3
 100.0%
1
 100.0%
 0
Hypersensitivity Number Analyzed 0 participants 0 participants 0 participants 0 participants
0 0 0 0
Adrenal Insufficiency Number Analyzed 3 participants 1 participants 0 participants 1 participants
3
 100.0%
1
 100.0%
 0
1
 100.0%
Hypothyroidism/Thyroiditis Number Analyzed 0 participants 0 participants 0 participants 1 participants
0 0 0
1
 100.0%
Diabetes Mellitus Number Analyzed 3 participants 0 participants 1 participants 0 participants
3
 100.0%
 0
1
 100.0%
 0
Hyperthyroidism Number Analyzed 0 participants 0 participants 0 participants 0 participants
0 0 0 0
Hypophysitis Number Analyzed 0 participants 1 participants 1 participants 0 participants
0
1
 100.0%
1
 100.0%
 0
6.Secondary Outcome
Title Number of Participants Who Received Hormone Replacement Therapy for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs)
Hide Description The number of participants who received Hormone Replacement Therapy for experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time Frame From first dose up to 100 days post last dose (up to approximately 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants who experienced at least one Grade 3 to 5 Immune-Mediate Event from the category
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Measure Type: Count of Participants
Unit of Measure: Participants
Pneumonitis Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
 0 0 0
Diarrhoea/Colitis Number Analyzed 8 participants 4 participants 2 participants 0 participants
8
 100.0%
3
  75.0%
2
 100.0%
 0
Hepatitis Number Analyzed 3 participants 1 participants 1 participants 1 participants
3
 100.0%
1
 100.0%
1
 100.0%
1
 100.0%
Nephritis and Renal Dysfunction Number Analyzed 0 participants 2 participants 0 participants 0 participants
0
2
 100.0%
 0 0
Rash Number Analyzed 7 participants 3 participants 1 participants 0 participants
7
 100.0%
3
 100.0%
1
 100.0%
 0
Hypersensitivity Number Analyzed 0 participants 0 participants 0 participants 0 participants
Adrenal Insufficiency Number Analyzed 3 participants 1 participants 0 participants 1 participants
2
  66.7%
1
 100.0%
 0
1
 100.0%
Hypothyroidism and Thyroiditis Number Analyzed 0 participants 0 participants 0 participants 0 participants
Diabetes Mellitus Number Analyzed 3 participants 0 participants 1 participants 0 participants
0
   0.0%
 0
1
 100.0%
 0
Hyperthyroidism Number Analyzed 0 participants 0 participants 0 participants 0 participants
Hypophysitis Number Analyzed 0 participants 1 participants 1 participants 0 participants
0
1
 100.0%
0
   0.0%
 0
7.Secondary Outcome
Title Number of Participants Who Received ≥ 40mg of Prednisone for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs)
Hide Description The number of participants who received ≥ 40mg of prednisone for high grade (grades 3-5) IMAEs. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time Frame From first dose up to 100 days post last dose (up to approximately 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Measure Type: Count of Participants
Unit of Measure: Participants
19
  17.9%
9
  17.3%
5
  17.9%
2
   8.0%
8.Secondary Outcome
Title Median Progression Free Survival (PFS)
Hide Description PFS is defined as the time from first dose to the date of the first documented progressive disease (PD) as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause whichever occur first. Progressive disease is defined as progression of existing non-target lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame From first dose to the date of the first documented progressive disease, up to approximately 12 months
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Hide Analysis Population Description
All Treated Participants
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 106 52 28 25
Median (95% Confidence Interval)
Unit of Measure: Months
4.8
(3.0 to 8.4)
3.7
(2.7 to 4.6)
8.5
(2.9 to 12.0)
3.6
(2.5 to 8.7)
9.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).
Time Frame From first dose up to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 26 months)
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Hide Analysis Population Description
All response evaluable participants: all treated participants who have baseline and at least one on-study evaluable tumor measurement.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 96 46 26 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
35.4
(25.9 to 45.8)
21.7
(10.9 to 36.4)
30.8
(14.3 to 51.8)
33.3
(13.3 to 59.0)
10.Secondary Outcome
Title Time to Response Rate (TRR)
Hide Description TTR is defined as the median percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).
Time Frame From the date of first dose to first documented CR or PR, up to approximately 15 months
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Hide Analysis Population Description
All response evaluable participants: all treated participants who have baseline and at least one on-study evaluable tumor measurement.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 96 46 26 18
Median (Full Range)
Unit of Measure: Months
2.8
(2.5 to 14.6)
2.8
(2.1 to 4.5)
2.8
(2.4 to 3.0)
4.5
(2.5 to 12.1)
11.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR is defined as the time between the date of first confirmed response to the date of the first documented tumor progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, whichever occurs first. DOR will be computed for participants who achieve partial response (PR) or complete response (CR) only. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (< 10mm short axis).
Time Frame From first confirmed response to the date of the first documented tumor progression or death, up to approximately 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
All response evaluable participants: all treated participants who have baseline and at least one on-study evaluable tumor measurement.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description:
Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses
Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
Overall Number of Participants Analyzed 96 46 26 18
Median (95% Confidence Interval)
Unit of Measure: Months
11.01 [1] 
(7.10 to NA)
37.68 [1] 
(10.87 to NA)
16.51
(3.88 to 47.87)
19.48
(6.28 to 20.57)
[1]
Upper limit not calculated due to insufficient number of events
Time Frame SAEs and NSAEs: From first dose to 100 days post last dose (up to approximately 29 months). Participants were assessed for All-cause mortality from their first dose to study completion (up to approximately 56 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4
Hide Arm/Group Description Nivolumab 6mg/kg IV plus, Ipilimumab 1mg/kg IV every 8 weeks alternating with Nivolumab 480 mg IV every 8 weeks, staggered every 4 weeks Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses Nivolumab 3mg/kg IV combined with Ipilimumab 1mg/kg IV every 3 weeks for 4 doses Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses
All-Cause Mortality
Cohort 1 Cohort 2 Cohort 3 Cohort 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   55/106 (51.89%)   29/52 (55.77%)   15/28 (53.57%)   20/25 (80.00%) 
Hide Serious Adverse Events
Cohort 1 Cohort 2 Cohort 3 Cohort 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   63/106 (59.43%)   29/52 (55.77%)   14/28 (50.00%)   17/25 (68.00%) 
Blood and lymphatic system disorders         
Anaemia † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Anaemia of chronic disease † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Disseminated intravascular coagulation † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Leukocytosis † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Splenic infarction † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Cardiac disorders         
Acute coronary syndrome † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Acute myocardial infarction † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Atrial fibrillation † 1  4/106 (3.77%)  1/52 (1.92%)  1/28 (3.57%)  0/25 (0.00%) 
Atrioventricular block complete † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Ischaemic cardiomyopathy † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Left ventricular failure † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Myocardial infarction † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Pericarditis † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Endocrine disorders         
Adrenal insufficiency † 1  4/106 (3.77%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Hypophysitis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Hypothyroidism † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Gastrointestinal disorders         
Ascites † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Colitis † 1  5/106 (4.72%)  2/52 (3.85%)  1/28 (3.57%)  0/25 (0.00%) 
Diarrhoea † 1  4/106 (3.77%)  1/52 (1.92%)  2/28 (7.14%)  0/25 (0.00%) 
Diverticular perforation † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Duodenal ulcer haemorrhage † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Dysphagia † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Faecaloma † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Ileus † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Incarcerated inguinal hernia † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Intussusception † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Lower gastrointestinal haemorrhage † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Nausea † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Pancreatitis † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Rectal haemorrhage † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Retroperitoneal haematoma † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Small intestinal haemorrhage † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Small intestinal obstruction † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Stomatitis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Upper gastrointestinal haemorrhage † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Vomiting † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
General disorders         
Asthenia † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Fatigue † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Non-cardiac chest pain † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Pyrexia † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Sudden death † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Systemic inflammatory response syndrome † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Hepatobiliary disorders         
Autoimmune hepatitis † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Cholelithiasis † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Drug-induced liver injury † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Immune-mediated hepatitis † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Immune system disorders         
Anaphylactic reaction † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Infections and infestations         
Cholecystitis infective † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Clostridium difficile infection † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Cryptosporidiosis infection † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Device related infection † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Diverticulitis † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Encephalitis † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Influenza † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Meningitis aseptic † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Pneumonia † 1  5/106 (4.72%)  2/52 (3.85%)  1/28 (3.57%)  0/25 (0.00%) 
Postoperative wound infection † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Pyelonephritis acute † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Sepsis † 1  3/106 (2.83%)  2/52 (3.85%)  1/28 (3.57%)  1/25 (4.00%) 
Septic shock † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Staphylococcal sepsis † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Urinary tract infection † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Viral infection † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Injury, poisoning and procedural complications         
Acetabulum fracture † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Clavicle fracture † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Femoral neck fracture † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Femur fracture † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Subdural haematoma † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Toxicity to various agents † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Investigations         
Alanine aminotransferase increased † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Aspartate aminotransferase increased † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Blood alkaline phosphatase increased † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Blood creatinine increased † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Body temperature increased † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
CSF white blood cell count increased † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Hepatic enzyme increased † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Lipase increased † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Transaminases increased † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Metabolism and nutrition disorders         
Acidosis † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Dehydration † 1  3/106 (2.83%)  0/52 (0.00%)  2/28 (7.14%)  0/25 (0.00%) 
Diabetic ketoacidosis † 1  2/106 (1.89%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Failure to thrive † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Hypercalcaemia † 1  2/106 (1.89%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Hyperglycaemia † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Hyperglycaemic hyperosmolar nonketotic syndrome † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Hyperkalaemia † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Hypokalaemia † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Hyponatraemia † 1  2/106 (1.89%)  2/52 (3.85%)  0/28 (0.00%)  0/25 (0.00%) 
Hypovolaemia † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Flank pain † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Immune-mediated arthritis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Myositis † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Pathological fracture † 1  1/106 (0.94%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Cancer pain † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Malignant neoplasm progression † 1  15/106 (14.15%)  6/52 (11.54%)  5/28 (17.86%)  5/25 (20.00%) 
Malignant pleural effusion † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Metastases to central nervous system † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Metastatic renal cell carcinoma † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Respiratory tract neoplasm † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Nervous system disorders         
Cerebellar infarction † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Dysarthria † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Encephalopathy † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Facial paralysis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Haemorrhage intracranial † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Hypoxic-ischaemic encephalopathy † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Metabolic encephalopathy † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Myasthenia gravis † 1  1/106 (0.94%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Presyncope † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Seizure † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Syncope † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Vasogenic cerebral oedema † 1  0/106 (0.00%)  0/52 (0.00%)  1/28 (3.57%)  0/25 (0.00%) 
Psychiatric disorders         
Mental status changes † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  2/25 (8.00%) 
Renal and urinary disorders         
Acute kidney injury † 1  2/106 (1.89%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Haematuria † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Nephritis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Nephrolithiasis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Renal failure † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure † 1  2/106 (1.89%)  2/52 (3.85%)  1/28 (3.57%)  0/25 (0.00%) 
Chronic obstructive pulmonary disease † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Dyspnoea † 1  2/106 (1.89%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
Haemoptysis † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Hypoxia † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Pleural effusion † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  2/25 (8.00%) 
Pneumonitis † 1  3/106 (2.83%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Pulmonary embolism † 1  1/106 (0.94%)  2/52 (3.85%)  0/28 (0.00%)  0/25 (0.00%) 
Respiratory arrest † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Vascular disorders         
Deep vein thrombosis † 1  0/106 (0.00%)  1/52 (1.92%)  0/28 (0.00%)  0/25 (0.00%) 
Hypotension † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  1/25 (4.00%) 
Lymphoedema † 1  1/106 (0.94%)  0/52 (0.00%)  0/28 (0.00%)  0/25 (0.00%) 
1
Term from vocabulary, MedDRA 24.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1 Cohort 2 Cohort 3 Cohort 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   103/106 (97.17%)   50/52 (96.15%)   27/28 (96.43%)   24/25 (96.00%) 
Blood and lymphatic system disorders         
Anaemia † 1  21/106 (19.81%)  6/52 (11.54%)  9/28 (32.14%)  4/25 (16.00%) 
Iron deficiency anaemia † 1  2/106 (1.89%)  0/52 (0.00%)  1/28 (3.57%)  2/25 (8.00%) 
Leukocytosis † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  2/25 (8.00%) 
Cardiac disorders         
Palpitations † 1  2/106 (1.89%)  0/52 (0.00%)  1/28 (3.57%)  2/25 (8.00%) 
Ear and labyrinth disorders         
Hypoacusis † 1  1/106 (0.94%)  3/52 (5.77%)  0/28 (0.00%)  0/25 (0.00%) 
Endocrine disorders         
Hyperthyroidism † 1  8/106 (7.55%)  3/52 (5.77%)  3/28 (10.71%)  3/25 (12.00%) 
Hypothyroidism † 1  19/106 (17.92%)  6/52 (11.54%)  9/28 (32.14%)  7/25 (28.00%) 
Eye disorders         
Dry eye † 1  2/106 (1.89%)  3/52 (5.77%)  0/28 (0.00%)  0/25 (0.00%) 
Vision blurred † 1  7/106 (6.60%)  2/52 (3.85%)  2/28 (7.14%)  1/25 (4.00%) 
Gastrointestinal disorders         
Abdominal distension † 1  5/106 (4.72%)  3/52 (5.77%)  0/28 (0.00%)  2/25 (8.00%) 
Abdominal pain † 1  17/106 (16.04%)  7/52 (13.46%)  6/28 (21.43%)  7/25 (28.00%) 
Abdominal pain lower † 1  2/106 (1.89%)  3/52 (5.77%)  0/28 (0.00%)  0/25 (0.00%) 
Abdominal pain upper † 1  6/106 (5.66%)  2/52 (3.85%)  0/28 (0.00%)  0/25 (0.00%) 
Constipation † 1  24/106 (22.64%)  14/52 (26.92%)  6/28 (21.43%)  7/25 (28.00%) 
Diarrhoea † 1  45/106 (42.45%)  19/52 (36.54%)  11/28 (39.29%)  9/25 (36.00%) 
Dry mouth † 1  10/106 (9.43%)  4/52 (7.69%)  3/28 (10.71%)  1/25 (4.00%) 
Dyspepsia † 1  9/106 (8.49%)  1/52 (1.92%)  0/28 (0.00%)  2/25 (8.00%) 
Dysphagia † 1  1/106 (0.94%)  2/52 (3.85%)  1/28 (3.57%)  2/25 (8.00%) 
Flatulence † 1  0/106 (0.00%)  1/52 (1.92%)  2/28 (7.14%)  0/25 (0.00%) 
Gastrooesophageal reflux disease † 1  6/106 (5.66%)  2/52 (3.85%)  1/28 (3.57%)  0/25 (0.00%) 
Nausea † 1  40/106 (37.74%)  20/52 (38.46%)  12/28 (42.86%)  6/25 (24.00%) 
Stomatitis † 1  9/106 (8.49%)  5/52 (9.62%)  1/28 (3.57%)  3/25 (12.00%) 
Vomiting † 1  24/106 (22.64%)  12/52 (23.08%)  3/28 (10.71%)  1/25 (4.00%) 
General disorders         
Asthenia † 1  11/106 (10.38%)  4/52 (7.69%)  4/28 (14.29%)  2/25 (8.00%) 
Chills † 1  10/106 (9.43%)  6/52 (11.54%)  3/28 (10.71%)  0/25 (0.00%) 
Fatigue † 1  62/106 (58.49%)  31/52 (59.62%)  14/28 (50.00%)  2/25 (8.00%) 
Localised oedema † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  2/25 (8.00%) 
Non-cardiac chest pain † 1  2/106 (1.89%)  3/52 (5.77%)  0/28 (0.00%)  3/25 (12.00%) 
Oedema peripheral † 1  23/106 (21.70%)  9/52 (17.31%)  6/28 (21.43%)  4/25 (16.00%) 
Pain † 1  4/106 (3.77%)  3/52 (5.77%)  0/28 (0.00%)  1/25 (4.00%) 
Peripheral swelling † 1  4/106 (3.77%)  0/52 (0.00%)  2/28 (7.14%)  0/25 (0.00%) 
Pyrexia † 1  13/106 (12.26%)  9/52 (17.31%)  3/28 (10.71%)  2/25 (8.00%) 
Immune system disorders         
Seasonal allergy † 1  6/106 (5.66%)  0/52 (0.00%)  2/28 (7.14%)  0/25 (0.00%) 
Infections and infestations         
Clostridium difficile infection † 1  0/106 (0.00%)  0/52 (0.00%)  0/28 (0.00%)  2/25 (8.00%) 
Diverticulitis † 1  2/106 (1.89%)  0/52 (0.00%)  2/28 (7.14%)  0/25 (0.00%) 
Nasopharyngitis † 1  3/106 (2.83%)  3/52 (5.77%)  0/28 (0.00%)  0/25 (0.00%) 
Oral candidiasis † 1  5/106 (4.72%)  3/52 (5.77%)  2/28 (7.14%)  1/25 (4.00%) 
Pneumonia † 1  6/106 (5.66%)  2/52 (3.85%)  1/28 (3.57%)  2/25 (8.00%) 
Sinusitis † 1  4/106 (3.77%)  3/52 (5.77%)  1/28 (3.57%)  1/25 (4.00%) 
Upper respiratory tract infection † 1  11/106 (10.38%)  4/52 (7.69%)  2/28 (7.14%)  2/25 (8.00%) 
Urinary tract infection † 1  7/106 (6.60%)  2/52 (3.85%)  4/28 (14.29%)  2/25 (8.00%) 
Injury, poisoning and procedural complications         
Fall † 1  10/106 (9.43%)  2/52 (3.85%)  1/28 (3.57%)  4/25 (16.00%) 
Infusion related reaction † 1  8/106 (7.55%)  2/52 (3.85%)  0/28 (0.00%)  3/25 (12.00%) 
Investigations         
Alanine aminotransferase increased † 1  15/106 (14.15%)  5/52 (9.62%)  2/28 (7.14%)  1/25 (4.00%) 
Amylase increased † 1  15/106 (14.15%)  6/52 (11.54%)  5/28 (17.86%)  3/25 (12.00%) 
Aspartate aminotransferase increased † 1  14/106 (13.21%)  6/52 (11.54%)  1/28 (3.57%)  3/25 (12.00%) 
Blood alkaline phosphatase increased † 1  10/106 (9.43%)  1/52 (1.92%)  1/28 (3.57%)  1/25 (4.00%) 
Blood creatinine increased † 1  21/106 (19.81%)  3/52 (5.77%)  5/28 (17.86%)  7/25 (28.00%) 
Blood thyroid stimulating hormone decreased † 1  3/106 (2.83%)  3/52 (5.77%)  0/28 (0.00%)  0/25 (0.00%) 
Blood thyroid stimulating hormone increased † 1  5/106 (4.72%)  2/52 (3.85%)  2/28 (7.14%)  1/25 (4.00%) 
Lipase increased † 1  23/106 (21.70%)  8/52 (15.38%)  6/28 (21.43%)  5/25 (20.00%) 
Weight decreased † 1  12/106 (11.32%)  10/52 (19.23%)  8/28 (28.57%)  6/25 (24.00%) 
Weight increased † 1  7/106 (6.60%)  2/52 (3.85%)  1/28 (3.57%)  0/25 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  26/106 (24.53%)  14/52 (26.92%)  5/28 (17.86%)  6/25 (24.00%) 
Dehydration † 1  15/106 (14.15%)  11/52 (21.15%)  6/28 (21.43%)  3/25 (12.00%) 
Hypercalcaemia † 1  5/106 (4.72%)  2/52 (3.85%)  1/28 (3.57%)  2/25 (8.00%) 
Hyperglycaemia † 1  12/106 (11.32%)  3/52 (5.77%)  2/28 (7.14%)  2/25 (8.00%) 
Hyperkalaemia † 1  6/106 (5.66%)  6/52 (11.54%)  0/28 (0.00%)  4/25 (16.00%) 
Hypoalbuminaemia † 1  11/106 (10.38%)  1/52 (1.92%)  3/28 (10.71%)  4/25 (16.00%) 
Hypocalcaemia † 1  7/106 (6.60%)  1/52 (1.92%)  1/28 (3.57%)  3/25 (12.00%) 
Hypoglycaemia † 1  3/106 (2.83%)  0/52 (0.00%)  2/28 (7.14%)  0/25 (0.00%) 
Hypokalaemia † 1  12/106 (11.32%)  4/52 (7.69%)  2/28 (7.14%)  1/25 (4.00%) 
Hypomagnesaemia † 1  14/106 (13.21%)  1/52 (1.92%)  5/28 (17.86%)  3/25 (12.00%) 
Hyponatraemia † 1  17/106 (16.04%)  7/52 (13.46%)  4/28 (14.29%)  4/25 (16.00%) 
Hypophosphataemia † 1  6/106 (5.66%)  0/52 (0.00%)  1/28 (3.57%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  29/106 (27.36%)  12/52 (23.08%)  7/28 (25.00%)  5/25 (20.00%) 
Back pain † 1  16/106 (15.09%)  10/52 (19.23%)  3/28 (10.71%)  5/25 (20.00%) 
Flank pain † 1  7/106 (6.60%)  8/52 (15.38%)  2/28 (7.14%)  1/25 (4.00%) 
Muscle spasms † 1  4/106 (3.77%)  2/52 (3.85%)  4/28 (14.29%)  1/25 (4.00%) 
Muscular weakness † 1  10/106 (9.43%)  7/52 (13.46%)  2/28 (7.14%)  2/25 (8.00%) 
Musculoskeletal chest pain † 1  3/106 (2.83%)  4/52 (7.69%)  0/28 (0.00%)  4/25 (16.00%) 
Musculoskeletal discomfort † 1  0/106 (0.00%)  1/52 (1.92%)  2/28 (7.14%)  0/25 (0.00%) 
Myalgia † 1  6/106 (5.66%)  5/52 (9.62%)  3/28 (10.71%)  0/25 (0.00%) 
Neck pain † 1  8/106 (7.55%)  1/52 (1.92%)  0/28 (0.00%)  1/25 (4.00%) 
Pain in extremity † 1  13/106 (12.26%)  3/52 (5.77%)  4/28 (14.29%)  3/25 (12.00%) 
Nervous system disorders         
Dizziness † 1  20/106 (18.87%)  8/52 (15.38%)  1/28 (3.57%)  0/25 (0.00%) 
Headache † 1  19/106 (17.92%)  12/52 (23.08%)  5/28 (17.86%)  2/25 (8.00%) 
Paraesthesia † 1  6/106 (5.66%)  1/52 (1.92%)  0/28 (0.00%)  2/25 (8.00%) 
Peripheral sensory neuropathy † 1  8/106 (7.55%)  1/52 (1.92%)  1/28 (3.57%)  0/25 (0.00%) 
Tremor † 1  2/106 (1.89%)  4/52 (7.69%)  1/28 (3.57%)  1/25 (4.00%) 
Psychiatric disorders         
Anxiety † 1  13/106 (12.26%)  6/52 (11.54%)  4/28 (14.29%)  4/25 (16.00%) 
Confusional state † 1  4/106 (3.77%)  2/52 (3.85%)  4/28 (14.29%)  1/25 (4.00%) 
Depression † 1  6/106 (5.66%)  5/52 (9.62%)  2/28 (7.14%)  3/25 (12.00%) 
Insomnia † 1  21/106 (19.81%)  7/52 (13.46%)  4/28 (14.29%)  2/25 (8.00%) 
Renal and urinary disorders         
Acute kidney injury † 1  2/106 (1.89%)  2/52 (3.85%)  4/28 (14.29%)  5/25 (20.00%) 
Haematuria † 1  3/106 (2.83%)  1/52 (1.92%)  0/28 (0.00%)  2/25 (8.00%) 
Proteinuria † 1  1/106 (0.94%)  0/52 (0.00%)  1/28 (3.57%)  2/25 (8.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1  32/106 (30.19%)  11/52 (21.15%)  7/28 (25.00%)  6/25 (24.00%) 
Dyspnoea † 1  22/106 (20.75%)  8/52 (15.38%)  3/28 (10.71%)  5/25 (20.00%) 
Dyspnoea exertional † 1  5/106 (4.72%)  6/52 (11.54%)  3/28 (10.71%)  0/25 (0.00%) 
Haemoptysis † 1  3/106 (2.83%)  0/52 (0.00%)  0/28 (0.00%)  2/25 (8.00%) 
Hiccups † 1  4/106 (3.77%)  1/52 (1.92%)  3/28 (10.71%)  0/25 (0.00%) 
Hypoxia † 1  2/106 (1.89%)  2/52 (3.85%)  1/28 (3.57%)  2/25 (8.00%) 
Nasal congestion † 1  6/106 (5.66%)  2/52 (3.85%)  2/28 (7.14%)  0/25 (0.00%) 
Oropharyngeal pain † 1  10/106 (9.43%)  2/52 (3.85%)  0/28 (0.00%)  2/25 (8.00%) 
Productive cough † 1  3/106 (2.83%)  3/52 (5.77%)  1/28 (3.57%)  2/25 (8.00%) 
Pulmonary embolism † 1  1/106 (0.94%)  4/52 (7.69%)  0/28 (0.00%)  0/25 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis acneiform † 1  6/106 (5.66%)  3/52 (5.77%)  1/28 (3.57%)  1/25 (4.00%) 
Dry skin † 1  10/106 (9.43%)  2/52 (3.85%)  1/28 (3.57%)  0/25 (0.00%) 
Hyperhidrosis † 1  4/106 (3.77%)  2/52 (3.85%)  2/28 (7.14%)  0/25 (0.00%) 
Pruritus † 1  32/106 (30.19%)  11/52 (21.15%)  9/28 (32.14%)  5/25 (20.00%) 
Rash † 1  8/106 (7.55%)  3/52 (5.77%)  2/28 (7.14%)  5/25 (20.00%) 
Rash macular † 1  6/106 (5.66%)  0/52 (0.00%)  2/28 (7.14%)  0/25 (0.00%) 
Rash maculo-papular † 1  13/106 (12.26%)  10/52 (19.23%)  6/28 (21.43%)  8/25 (32.00%) 
Rash papular † 1  3/106 (2.83%)  1/52 (1.92%)  0/28 (0.00%)  2/25 (8.00%) 
Rash pruritic † 1  12/106 (11.32%)  5/52 (9.62%)  3/28 (10.71%)  2/25 (8.00%) 
Vascular disorders         
Hypertension † 1  9/106 (8.49%)  6/52 (11.54%)  2/28 (7.14%)  2/25 (8.00%) 
Hypotension † 1  11/106 (10.38%)  5/52 (9.62%)  4/28 (14.29%)  3/25 (12.00%) 
1
Term from vocabulary, MedDRA 24.1
†
Indicates events were collected by systematic assessment
[Not Specified]
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: NCT02982954    
Other Study ID Numbers: CA209-920
First Submitted: December 2, 2016
First Posted: December 6, 2016
Results First Submitted: May 4, 2021
Results First Posted: October 14, 2021
Last Update Posted: November 1, 2022