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An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma (CheckMate 374)

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ClinicalTrials.gov Identifier: NCT02596035
Recruitment Status : Completed
First Posted : November 4, 2015
Results First Posted : August 28, 2019
Last Update Posted : October 27, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Renal Cell Carcinoma
Intervention Drug: Nivolumab
Enrollment 197
Recruitment Details  
Pre-assignment Details 142 Participants were treated
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Period Title: Overall Study
Started 97 44 1
Completed 0 0 0
Not Completed 97 44 1
Reason Not Completed
Disease Progression             64             32             1
study drug toxicity             12             3             0
AE unrelated to study drug             5             2             0
participant request to discontinue study treatment             2             0             0
participant withdrew consent             2             2             0
Poor/Non Comlpiance             0             1             0
participant no longer meets study criteria             1             0             0
other reasons             11             4             0
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis Total
Hide Arm/Group Description Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Total of all reporting groups
Overall Number of Baseline Participants 97 44 1 142
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 97 participants 44 participants 1 participants 142 participants
64.7  (10.33) 61.4  (12.88) 32 [1]   (NA) 63.5  (11.52)
[1]
Only 1 participant was evaluable in this arm.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 44 participants 1 participants 142 participants
Female
31
  32.0%
12
  27.3%
1
 100.0%
44
  31.0%
Male
66
  68.0%
32
  72.7%
0
   0.0%
98
  69.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 44 participants 1 participants 142 participants
Hispanic or Latino
11
  11.3%
4
   9.1%
1
 100.0%
16
  11.3%
Not Hispanic or Latino
86
  88.7%
39
  88.6%
0
   0.0%
125
  88.0%
Unknown or Not Reported
0
   0.0%
1
   2.3%
0
   0.0%
1
   0.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 44 participants 1 participants 142 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   5.2%
8
  18.2%
0
   0.0%
13
   9.2%
White
90
  92.8%
34
  77.3%
1
 100.0%
125
  88.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   2.1%
2
   4.5%
0
   0.0%
4
   2.8%
1.Primary Outcome
Title Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs)
Hide Description IMAEs were tabulated using worst grade per Common Terminology Criteria for Adverse Events, National Cancer Institute (NCI CTCAE) Version 4.0 criteria by system organ class and MedDRA version 20.1 preferred term.
Time Frame Up to 100 days of the last dose of study drug (Approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Measure Type: Number
Unit of Measure: Percentage of participants
Hepatitis (Grade 3-4) 4.1 0 0
Hepatitis (Grade 5) 0 0 0
Adrenal Insufficiency (Grade 3-4) 1 0 0
Adrenal Insufficiency (Grade 5) 0 0 0
Nephritis And Renal Dysfunction (Grade 3-4) 1 0 0
Nephritis And Renal Dysfunction (Grade 5) 0 0 0
Rash (Grade 3-4) 1 0 0
Rash (Grade 5) 0 0 0
Diabetes mellitus (Grade 3-4) 3.1 0 0
Diabetes mellitus (Grade 5) 0 0 0
Hypothyroidism (Grade 3-4) 0 0 0
Hypothyroidism (Grade 5) 0 0 0
Hypophysitis (Grade 3-4) 0 0 0
Hypophysitis (Grade 5) 0 0 0
Pneumonitis (Grade 3-4) 0 0 0
Pneumonitis (Grade 5) 0 0 0
Hypersensitivity (Grade 3-4) 0 0 0
Hypersensitivity (Grade 5) 0 0 0
Diarrhea/Colitis (Grade 3-4) 1 0 0
Diarrhea/Colitis (Grade 5) 0 0 0
Hyperthyroidism (Grade 3-4) 0 0 0
Hyperthyroidism (Grade 5) 0 0 0
2.Secondary Outcome
Title Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events
Hide Description Time to onset was calculated from first dosing date to the event onset date. If a participant never experienced the given AE, the participant will be censored at the last contact date.
Time Frame Up to 100 days of the last dose of study drug (Approximately 10 months up to 26 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Median (Full Range)
Unit of Measure: Days
Adrenal Insufficiency Number Analyzed 1 participants 0 participants 0 participants
76.0
(76 to 76)
Diabetes Mellitus Number Analyzed 2 participants 0 participants 0 participants
89.0
(46 to 805)
Hepatitis Number Analyzed 4 participants 0 participants 0 participants
84.5
(47 to 448)
Nephritis And Renal Dysfunction Number Analyzed 1 participants 0 participants 0 participants
43.0
(43 to 43)
Rash Number Analyzed 1 participants 0 participants 0 participants
7.0
(7 to 7)
Diarrhea/Colitis Number Analyzed 97 participants 0 participants 0 participants
645.0
(645.0 to 645.0)
3.Secondary Outcome
Title Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events
Hide Description Time-to resolution of grade 3-5 AE was defined as the longest time from onset to complete resolution or improvement to the grade at baseline among all clustered select AEs in the category experienced by the participant. Events which worsened into grade 5 events (death) or have a resolution date equal to the date of death are considered unresolved. If a clustered AE is considered as unresolved, the resolution date will be censored to the last known date alive.
Time Frame From onset of grade 3-5 IMAEs to resolution of IMAEs (Approximately 4 years and 7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Median (Full Range)
Unit of Measure: Days
Hepatitis Number Analyzed 4 participants 0 participants 0 participants
31.5
(15 to 75)
Nephritis And Renal Dysfunction Number Analyzed 3 participants 0 participants 0 participants
22.0
(6 to 54)
Rash Number Analyzed 1 participants 0 participants 0 participants
23.0
(23 to 23)
Diarrhea/Colitis Number Analyzed 1 participants 0 participants 0 participants
154.0
(154 to 154)
Adrenal Insufficiency Number Analyzed 1 participants 0 participants 0 participants
NA [1] 
(NA to NA)
[1]
0 Participants Resolved
4.Secondary Outcome
Title Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade)
Hide Description Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
Time Frame Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Measure Type: Number
Unit of Measure: Percentage of participants
Participants with Pneumonitis Number Analyzed 3 participants 3 participants 0 participants
66.7 0
Participants with Diarrhea/Colitis Number Analyzed 19 participants 8 participants 0 participants
5.3 0
Participants with Hepatitis Number Analyzed 12 participants 2 participants 0 participants
41.7 0
Participants with Adrenal Insufficiency Number Analyzed 1 participants 0 participants 0 participants
100
Participants with Nephritis And Renal Dysfunction Number Analyzed 22 participants 3 participants 0 participants
13.6 33.3
Participants with Rash Number Analyzed 31 participants 8 participants 0 participants
38.7 25.0
Participants with Hypersensitivity Number Analyzed 3 participants 0 participants 0 participants
66.7
Participants with Hyperthyroidism Number Analyzed 8 participants 2 participants 0 participants
12.5 0
Participants with Hypophysitis Number Analyzed 0 participants 1 participants 0 participants
100.0
5.Secondary Outcome
Title Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event
Hide Description Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
Time Frame Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Measure Type: Number
Unit of Measure: Percentage of participants
Participants with Pneumonitis Number Analyzed 3 participants 3 participants 0 participants
66.7 0
Participants with Diarrhea/Colitis Number Analyzed 19 participants 8 participants 0 participants
5.3 0
Participants with Hepatitis Number Analyzed 12 participants 2 participants 0 participants
41.7 0
Participants with Adrenal Insufficiency Number Analyzed 1 participants 0 participants 0 participants
0
Participants with Nephritis And Renal Dysfunction Number Analyzed 22 participants 3 participants 0 participants
9.1 0
Participants with Rash Number Analyzed 31 participants 8 participants 0 participants
6.5 0
Participants with Hypersensitivity Number Analyzed 3 participants 0 participants 0 participants
66.7
Participants with Hyperthyroidism Number Analyzed 8 participants 2 participants 0 participants
12.5 0
Participants with Hypophysitis Number Analyzed 0 participants 1 participants 0 participants
100.0
6.Secondary Outcome
Title Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event
Hide Description Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil.
Time Frame From the initiation of Immune modulating medication to discontinuation (approximately 4 years and 9 months).)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Median (Full Range)
Unit of Measure: Weeks
Pneumonitis Number Analyzed 2 participants 0 participants 0 participants
111.07
(8.1 to 214.0)
Diarrhea/Colitis Number Analyzed 1 participants 0 participants 0 participants
7.9
(7.9 to 7.9)
Hepatitis Number Analyzed 5 participants 0 participants 0 participants
7.00
(1.4 to 230.3)
Adrenal Insufficiency Number Analyzed 1 participants 0 participants 0 participants
241.14
(241.14 to 241.14)
Nephritis And Renal Dysfunction Number Analyzed 3 participants 1 participants 0 participants
1.14
(0.1 to 7.4)
1.9
(1.9 to 1.9)
Rash Number Analyzed 12 participants 2 participants 0 participants
9.29
(2.1 to 93.9)
137.43
(17.6 to 257.3)
Hypersensitivity Number Analyzed 2 participants 0 participants 0 participants
0.1
(0.1 to 0.1)
Hyperthyroidism Number Analyzed 1 participants 0 participants 0 participants
8.4
(8.4 to 8.4)
Hypophysitis Number Analyzed 0 participants 1 participants 0 participants
81.9
(81.9 to 81.9)
7.Secondary Outcome
Title Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication
Hide Description Percentage of participants with a resolution of IMAEs after initiating immune modulating medication.
Time Frame Up to 100 days of the last dose of study drug (Approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all treated participants who received any dose of nivolumab. Here, 'number analyzed' signifies those participants who were evaluable for specified categories.
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis
Hide Arm/Group Description:
Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion.
Overall Number of Participants Analyzed 97 44 1
Measure Type: Number
Unit of Measure: Percentage of participants
Pneumonitis Number Analyzed 2 participants 0 participants 0 participants
100
Diarrhea/Colitis Number Analyzed 1 participants 0 participants 0 participants
100
Hepatitis Number Analyzed 5 participants 0 participants 0 participants
100
Adrenal Insufficiency Number Analyzed 1 participants 0 participants 0 participants
0
Nephritis And Renal Dysfunction Number Analyzed 3 participants 1 participants 0 participants
66.7 0
Rash Number Analyzed 12 participants 2 participants 0 participants
83.3 50
Hypersensitivity Number Analyzed 2 participants 0 participants 0 participants
100
Hyperthyroidism Number Analyzed 1 participants 0 participants 0 participants
0
Hypophysitis Number Analyzed 0 participants 1 participants 0 participants
0
Time Frame Adverse events were reported between first dose and 30 days after last dose of study drug: Approximately 4 years and 7 months All Cause Mortality was calculated from first patient first visit to last patient last visit. Approximately 5 years and 4.5 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Clear Cell Histology Non-Clear Cell Histology Brain Metastasis Total
Hide Arm/Group Description Participants with predominant clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion Participants with non-clear cell histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Participants with brain metastases regardless of histology received Nivolumab at a dose of 240 mg Q2W by a 30-minute IV infusion. Total Participants
All-Cause Mortality
Clear Cell Histology Non-Clear Cell Histology Brain Metastasis Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   63/97 (64.95%)   29/44 (65.91%)   1/1 (100.00%)   93/142 (65.49%) 
Hide Serious Adverse Events
Clear Cell Histology Non-Clear Cell Histology Brain Metastasis Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   54/97 (55.67%)   19/44 (43.18%)   0/1 (0.00%)   73/142 (51.41%) 
Blood and lymphatic system disorders         
Anaemia † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Cardiac disorders         
Atrial fibrillation † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Atrial flutter † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Atrioventricular block first degree † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Cardiac failure congestive † 1  1/97 (1.03%)  1/44 (2.27%)  0/1 (0.00%)  2/142 (1.41%) 
Cardio-respiratory arrest † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Cardiogenic shock † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Myocardial infarction † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Pericarditis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Endocrine disorders         
Adrenocortical insufficiency acute † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Gastrointestinal disorders         
Abdominal pain lower † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Abdominal pain upper † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Constipation † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Erosive oesophagitis † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Ileus † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Lower gastrointestinal haemorrhage † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Vomiting † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
General disorders         
Asthenia † 1  1/97 (1.03%)  1/44 (2.27%)  0/1 (0.00%)  2/142 (1.41%) 
Mucosal inflammation † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Non-cardiac chest pain † 1  1/97 (1.03%)  1/44 (2.27%)  0/1 (0.00%)  2/142 (1.41%) 
Hepatobiliary disorders         
Cholelithiasis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Hepatic function abnormal † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Hyperbilirubinaemia † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Infections and infestations         
Bacterial sepsis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Cellulitis staphylococcal † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Cystitis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Epididymitis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Norovirus infection † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Pneumonia † 1  4/97 (4.12%)  1/44 (2.27%)  0/1 (0.00%)  5/142 (3.52%) 
Sepsis † 1  2/97 (2.06%)  2/44 (4.55%)  0/1 (0.00%)  4/142 (2.82%) 
Septic shock † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Sinusitis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Urinary tract infection † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Urosepsis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Injury, poisoning and procedural complications         
Cervical vertebral fracture † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Femur fracture † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Investigations         
Alanine aminotransferase increased † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Aspartate aminotransferase increased † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Blood creatinine increased † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Lipase increased † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Dehydration † 1  3/97 (3.09%)  0/44 (0.00%)  0/1 (0.00%)  3/142 (2.11%) 
Diabetic ketoacidosis † 1  3/97 (3.09%)  0/44 (0.00%)  0/1 (0.00%)  3/142 (2.11%) 
Hypercalcaemia † 1  3/97 (3.09%)  0/44 (0.00%)  0/1 (0.00%)  3/142 (2.11%) 
Hyperkalaemia † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Hyponatraemia † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Back pain † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Bone pain † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Flank pain † 1  1/97 (1.03%)  1/44 (2.27%)  0/1 (0.00%)  2/142 (1.41%) 
Muscular weakness † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Spinal stenosis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Cancer pain † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Colon cancer † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Intraductal proliferative breast lesion † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Malignant neoplasm progression † 1  18/97 (18.56%)  11/44 (25.00%)  0/1 (0.00%)  29/142 (20.42%) 
Neoplasm progression † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Tumour pseudoprogression † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Nervous system disorders         
Ataxia † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Cognitive disorder † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Haemorrhage intracranial † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Intracranial mass † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Ischaemic stroke † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Myasthenia gravis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Seizure † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Toxic encephalopathy † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Psychiatric disorders         
Confusional state † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Hallucination † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Mental status changes † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Renal and urinary disorders         
Acute kidney injury † 1  3/97 (3.09%)  2/44 (4.55%)  0/1 (0.00%)  5/142 (3.52%) 
Nephritis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Urinary retention † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Urinary tract obstruction † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Reproductive system and breast disorders         
Scrotal oedema † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Chronic respiratory failure † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Dyspnoea † 1  2/97 (2.06%)  1/44 (2.27%)  0/1 (0.00%)  3/142 (2.11%) 
Pleural effusion † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Pneumonia aspiration † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Pneumonitis † 1  2/97 (2.06%)  0/44 (0.00%)  0/1 (0.00%)  2/142 (1.41%) 
Pulmonary embolism † 1  0/97 (0.00%)  3/44 (6.82%)  0/1 (0.00%)  3/142 (2.11%) 
Respiratory failure † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Vascular disorders         
Deep vein thrombosis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
Peripheral embolism † 1  0/97 (0.00%)  1/44 (2.27%)  0/1 (0.00%)  1/142 (0.70%) 
Vena cava thrombosis † 1  1/97 (1.03%)  0/44 (0.00%)  0/1 (0.00%)  1/142 (0.70%) 
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Clear Cell Histology Non-Clear Cell Histology Brain Metastasis Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   91/97 (93.81%)   41/44 (93.18%)   1/1 (100.00%)   133/142 (93.66%) 
Blood and lymphatic system disorders         
Anaemia † 1  19/97 (19.59%)  5/44 (11.36%)  0/1 (0.00%)  24/142 (16.90%) 
Ear and labyrinth disorders         
Ear pain † 1  2/97 (2.06%)  3/44 (6.82%)  0/1 (0.00%)  5/142 (3.52%) 
Endocrine disorders         
Hyperthyroidism † 1  8/97 (8.25%)  2/44 (4.55%)  0/1 (0.00%)  10/142 (7.04%) 
Hypothyroidism † 1  9/97 (9.28%)  3/44 (6.82%)  0/1 (0.00%)  12/142 (8.45%) 
Eye disorders         
Vision blurred † 1  4/97 (4.12%)  1/44 (2.27%)  1/1 (100.00%)  6/142 (4.23%) 
Gastrointestinal disorders         
Abdominal distension † 1  4/97 (4.12%)  6/44 (13.64%)  0/1 (0.00%)  10/142 (7.04%) 
Abdominal pain † 1  11/97 (11.34%)  5/44 (11.36%)  0/1 (0.00%)  16/142 (11.27%) 
Abdominal pain upper † 1  6/97 (6.19%)  2/44 (4.55%)  0/1 (0.00%)  8/142 (5.63%) 
Constipation † 1  25/97 (25.77%)  13/44 (29.55%)  0/1 (0.00%)  38/142 (26.76%) 
Diarrhoea † 1  18/97 (18.56%)  8/44 (18.18%)  0/1 (0.00%)  26/142 (18.31%) 
Dry mouth † 1  8/97 (8.25%)  2/44 (4.55%)  0/1 (0.00%)  10/142 (7.04%) 
Gastrooesophageal reflux disease † 1  3/97 (3.09%)  5/44 (11.36%)  0/1 (0.00%)  8/142 (5.63%) 
Nausea † 1  23/97 (23.71%)  17/44 (38.64%)  0/1 (0.00%)  40/142 (28.17%) 
Stomatitis † 1  5/97 (5.15%)  0/44 (0.00%)  0/1 (0.00%)  5/142 (3.52%) 
Vomiting † 1  18/97 (18.56%)  6/44 (13.64%)  0/1 (0.00%)  24/142 (16.90%) 
General disorders         
Asthenia † 1  8/97 (8.25%)  3/44 (6.82%)  0/1 (0.00%)  11/142 (7.75%) 
Chills † 1  5/97 (5.15%)  5/44 (11.36%)  0/1 (0.00%)  10/142 (7.04%) 
Fatigue † 1  41/97 (42.27%)  16/44 (36.36%)  0/1 (0.00%)  57/142 (40.14%) 
Non-cardiac chest pain † 1  7/97 (7.22%)  0/44 (0.00%)  0/1 (0.00%)  7/142 (4.93%) 
Oedema peripheral † 1  14/97 (14.43%)  5/44 (11.36%)  0/1 (0.00%)  19/142 (13.38%) 
Pain † 1  6/97 (6.19%)  4/44 (9.09%)  0/1 (0.00%)  10/142 (7.04%) 
Pyrexia † 1  9/97 (9.28%)  5/44 (11.36%)  1/1 (100.00%)  15/142 (10.56%) 
Infections and infestations         
Nasopharyngitis † 1  5/97 (5.15%)  1/44 (2.27%)  0/1 (0.00%)  6/142 (4.23%) 
Sinusitis † 1  5/97 (5.15%)  0/44 (0.00%)  0/1 (0.00%)  5/142 (3.52%) 
Upper respiratory tract infection † 1  13/97 (13.40%)  5/44 (11.36%)  0/1 (0.00%)  18/142 (12.68%) 
Urinary tract infection † 1  13/97 (13.40%)  5/44 (11.36%)  0/1 (0.00%)  18/142 (12.68%) 
Investigations         
Alanine aminotransferase increased † 1  7/97 (7.22%)  1/44 (2.27%)  0/1 (0.00%)  8/142 (5.63%) 
Aspartate aminotransferase increased † 1  8/97 (8.25%)  2/44 (4.55%)  0/1 (0.00%)  10/142 (7.04%) 
Blood alkaline phosphatase increased † 1  5/97 (5.15%)  2/44 (4.55%)  0/1 (0.00%)  7/142 (4.93%) 
Blood creatinine increased † 1  17/97 (17.53%)  1/44 (2.27%)  0/1 (0.00%)  18/142 (12.68%) 
Blood thyroid stimulating hormone increased † 1  4/97 (4.12%)  3/44 (6.82%)  0/1 (0.00%)  7/142 (4.93%) 
Weight decreased † 1  13/97 (13.40%)  6/44 (13.64%)  0/1 (0.00%)  19/142 (13.38%) 
Weight increased † 1  8/97 (8.25%)  2/44 (4.55%)  0/1 (0.00%)  10/142 (7.04%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  25/97 (25.77%)  9/44 (20.45%)  0/1 (0.00%)  34/142 (23.94%) 
Dehydration † 1  8/97 (8.25%)  5/44 (11.36%)  0/1 (0.00%)  13/142 (9.15%) 
Hyperglycaemia † 1  5/97 (5.15%)  0/44 (0.00%)  0/1 (0.00%)  5/142 (3.52%) 
Hyperkalaemia † 1  8/97 (8.25%)  3/44 (6.82%)  0/1 (0.00%)  11/142 (7.75%) 
Hypokalaemia † 1  2/97 (2.06%)  4/44 (9.09%)  0/1 (0.00%)  6/142 (4.23%) 
Hyponatraemia † 1  6/97 (6.19%)  3/44 (6.82%)  0/1 (0.00%)  9/142 (6.34%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  24/97 (24.74%)  12/44 (27.27%)  0/1 (0.00%)  36/142 (25.35%) 
Back pain † 1  22/97 (22.68%)  16/44 (36.36%)  0/1 (0.00%)  38/142 (26.76%) 
Flank pain † 1  5/97 (5.15%)  4/44 (9.09%)  0/1 (0.00%)  9/142 (6.34%) 
Groin pain † 1  5/97 (5.15%)  1/44 (2.27%)  0/1 (0.00%)  6/142 (4.23%) 
Muscle spasms † 1  5/97 (5.15%)  0/44 (0.00%)  0/1 (0.00%)  5/142 (3.52%) 
Muscular weakness † 1  14/97 (14.43%)  4/44 (9.09%)  0/1 (0.00%)  18/142 (12.68%) 
Musculoskeletal chest pain † 1  8/97 (8.25%)  1/44 (2.27%)  0/1 (0.00%)  9/142 (6.34%) 
Myalgia † 1  3/97 (3.09%)  5/44 (11.36%)  0/1 (0.00%)  8/142 (5.63%) 
Neck pain † 1  5/97 (5.15%)  1/44 (2.27%)  0/1 (0.00%)  6/142 (4.23%) 
Pain in extremity † 1  13/97 (13.40%)  3/44 (6.82%)  0/1 (0.00%)  16/142 (11.27%) 
Nervous system disorders         
Dizziness † 1  10/97 (10.31%)  4/44 (9.09%)  0/1 (0.00%)  14/142 (9.86%) 
Headache † 1  8/97 (8.25%)  5/44 (11.36%)  1/1 (100.00%)  14/142 (9.86%) 
Psychiatric disorders         
Anxiety † 1  8/97 (8.25%)  3/44 (6.82%)  0/1 (0.00%)  11/142 (7.75%) 
Confusional state † 1  6/97 (6.19%)  0/44 (0.00%)  0/1 (0.00%)  6/142 (4.23%) 
Depression † 1  8/97 (8.25%)  1/44 (2.27%)  0/1 (0.00%)  9/142 (6.34%) 
Insomnia † 1  13/97 (13.40%)  3/44 (6.82%)  1/1 (100.00%)  17/142 (11.97%) 
Renal and urinary disorders         
Haematuria † 1  8/97 (8.25%)  4/44 (9.09%)  0/1 (0.00%)  12/142 (8.45%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1  25/97 (25.77%)  13/44 (29.55%)  0/1 (0.00%)  38/142 (26.76%) 
Dysphonia † 1  1/97 (1.03%)  3/44 (6.82%)  0/1 (0.00%)  4/142 (2.82%) 
Dyspnoea † 1  16/97 (16.49%)  7/44 (15.91%)  0/1 (0.00%)  23/142 (16.20%) 
Haemoptysis † 1  5/97 (5.15%)  0/44 (0.00%)  0/1 (0.00%)  5/142 (3.52%) 
Hypoxia † 1  4/97 (4.12%)  4/44 (9.09%)  0/1 (0.00%)  8/142 (5.63%) 
Nasal congestion † 1  8/97 (8.25%)  3/44 (6.82%)  0/1 (0.00%)  11/142 (7.75%) 
Oropharyngeal pain † 1  6/97 (6.19%)  1/44 (2.27%)  0/1 (0.00%)  7/142 (4.93%) 
Pneumonitis † 1  1/97 (1.03%)  3/44 (6.82%)  0/1 (0.00%)  4/142 (2.82%) 
Productive cough † 1  6/97 (6.19%)  0/44 (0.00%)  0/1 (0.00%)  6/142 (4.23%) 
Skin and subcutaneous tissue disorders         
Dry skin † 1  5/97 (5.15%)  2/44 (4.55%)  0/1 (0.00%)  7/142 (4.93%) 
Palmar-plantar erythrodysaesthesia syndrome † 1  1/97 (1.03%)  3/44 (6.82%)  0/1 (0.00%)  4/142 (2.82%) 
Pruritus † 1  16/97 (16.49%)  11/44 (25.00%)  0/1 (0.00%)  27/142 (19.01%) 
Rash † 1  14/97 (14.43%)  3/44 (6.82%)  0/1 (0.00%)  17/142 (11.97%) 
Rash maculo-papular † 1  5/97 (5.15%)  1/44 (2.27%)  0/1 (0.00%)  6/142 (4.23%) 
Rash pruritic † 1  9/97 (9.28%)  1/44 (2.27%)  0/1 (0.00%)  10/142 (7.04%) 
Vascular disorders         
Hypertension † 1  5/97 (5.15%)  2/44 (4.55%)  0/1 (0.00%)  7/142 (4.93%) 
Hypotension † 1  2/97 (2.06%)  3/44 (6.82%)  0/1 (0.00%)  5/142 (3.52%) 
1
Term from vocabulary, MedDRA 24.0
†
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
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02596035    
Other Study ID Numbers: CA209-374
2015-003286-28 ( EudraCT Number )
First Submitted: November 2, 2015
First Posted: November 4, 2015
Results First Submitted: April 29, 2019
Results First Posted: August 28, 2019
Last Update Posted: October 27, 2022