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Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)

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: NCT01472081
Recruitment Status : Active, not recruiting
First Posted : November 16, 2011
Results First Posted : August 2, 2019
Last Update Posted : April 22, 2020
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
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
Conditions Renal Cell Carcinoma
Clear-cell Metastatic Renal Cell Carcinoma
Interventions Biological: Nivolumab
Biological: Pazopanib
Drug: Sunitinib
Biological: Ipilimumab
Enrollment 194
Recruitment Details  
Pre-assignment Details 194 participants were enrolled; 153 were treated. Participants were enrolled but not treated due to the following reasons: withdrawal of consent (n=5), no longer met study criteria (n=32), administrative reason by sponsor (n=1), or other reasons (n=3)
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Period Title: Overall Study
Started 7 26 20 47 47 6
Completed 0 0 0 1 0 0
Not Completed 7 26 20 46 47 6
Reason Not Completed
Continuing treatment at time of analysis             1             4             1             8             9             0
Disease Progression             4             10             12             31             22             3
Study drug toxicity             2             9             4             6             13             2
Death             0             0             0             0             1             0
Adverse Event unrelated to study drug             0             0             0             0             1             0
Withdrawal by Subject             0             0             0             0             0             1
Poor/non-compliance             0             0             1             0             1             0
No longer meets study criteria             0             0             1             0             0             0
Subject request to discontinue treatment             0             3             1             1             0             0
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3 Total
Hide Arm/Group Description Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Total of all reporting groups
Overall Number of Baseline Participants 7 26 20 47 47 6 153
Hide Baseline Analysis Population Description
All treated participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 26 participants 20 participants 47 participants 47 participants 6 participants 153 participants
56.9  (11.36) 58.3  (8.62) 56.3  (8.52) 53.0  (8.97) 55.6  (11.58) 54.8  (2.71) 55.4  (9.71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 26 participants 20 participants 47 participants 47 participants 6 participants 153 participants
Female
0
   0.0%
7
  26.9%
2
  10.0%
14
  29.8%
9
  19.1%
1
  16.7%
33
  21.6%
Male
7
 100.0%
19
  73.1%
18
  90.0%
33
  70.2%
38
  80.9%
5
  83.3%
120
  78.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 26 participants 20 participants 47 participants 47 participants 6 participants 153 participants
Hispanic or Latino
0
   0.0%
2
   7.7%
0
   0.0%
1
   2.1%
2
   4.3%
1
  16.7%
6
   3.9%
Not Hispanic or Latino
7
 100.0%
22
  84.6%
18
  90.0%
42
  89.4%
40
  85.1%
5
  83.3%
134
  87.6%
Unknown or Not Reported
0
   0.0%
2
   7.7%
2
  10.0%
4
   8.5%
5
  10.6%
0
   0.0%
13
   8.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 26 participants 20 participants 47 participants 47 participants 6 participants 153 participants
American Indian or Alaska Native
0
   0.0%
1
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.7%
Asian
0
   0.0%
1
   3.8%
0
   0.0%
2
   4.3%
0
   0.0%
0
   0.0%
3
   2.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  14.3%
1
   3.8%
1
   5.0%
1
   2.1%
1
   2.1%
0
   0.0%
5
   3.3%
White
6
  85.7%
22
  84.6%
18
  90.0%
44
  93.6%
45
  95.7%
6
 100.0%
141
  92.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   3.8%
1
   5.0%
0
   0.0%
1
   2.1%
0
   0.0%
3
   2.0%
1.Primary Outcome
Title Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation
Hide Description Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
Time Frame From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description:
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Overall Number of Participants Analyzed 7 26 20 47 47 6
Measure Type: Number
Unit of Measure: participants
All-causality SAEs (any grade) 3 16 13 29 30 4
All-causality SAEs (grade 3-4) 1 14 10 20 24 4
Drug-related SAEs (any grade) 2 12 2 11 16 3
Drug-related SAEs (grade 3-4) 0 10 2 9 16 3
All-cause AEs led to discontinuation (any grade) 3 10 5 5 15 2
All-cause AEs led to discontinuation (grade 3-4) 2 9 4 3 11 0
All-Causality AEs (any grade) 7 26 20 47 47 6
All-Causality AEs (grade 3-4) 6 24 16 33 34 6
Drug-related AEs (any grade) 7 26 20 43 45 6
Drug-related AEs (grade 3-4) 5 22 14 18 29 5
2.Secondary Outcome
Title Best Overall Response Rate (BOR)
Hide Description

BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first.

CR = Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum 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. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time Frame From date of first dose to date of disease progression or subsequent anti-cancer therapy, whichever occurred first (assessed up to March 2016, approximately 49 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description:
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Overall Number of Participants Analyzed 7 26 20 47 47 6
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response 1 0 1 5 0 0
Partial Response 5 11 8 14 19 0
Stable Disease 1 11 7 19 17 5
Progressive Disease 0 1 4 8 8 1
Unable to Determine 0 3 0 1 3 0
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description

ORR was defined as the proportion of participants who achieved a BOR of either complete response (CR) or partial response (PR) in the population of interest.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time Frame From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description:
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Overall Number of Participants Analyzed 7 26 20 47 47 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
85.7
(42.1 to 99.6)
42.3
(23.4 to 63.1)
45.0
(23.1 to 68.5)
40.4
(26.4 to 55.7)
40.4
(26.4 to 55.7)
0
(0 to 0)
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was computed for participants with BOR of CR or PR only, and defined as the time between the date of first documented objective response and the date of the first subsequent disease progression or death. Participants who remained alive and had not progressed were censored on the last tumor assessment date (prior to subsequent cancer therapy).
Time Frame From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description:
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Overall Number of Participants Analyzed 7 26 20 47 47 6
Median (95% Confidence Interval)
Unit of Measure: weeks
45.6 [1] 
(18.14 to NA)
78.1 [1] 
(36.14 to NA)
30.1
(12.14 to 174.14)
88.7 [1] 
(37.14 to NA)
85.9 [1] 
(35.14 to NA)
NA [2] 
(NA to NA)
[1]
Upper 95% CI not reached
[2]
No participants in this arm achieved BOR of PR or CR
5.Secondary Outcome
Title Rate of Progression-free Survival (PFS) at Week 24
Hide Description Rate of PFS at week 24 was defined as the proportion of participants remaining progression free or surviving at 24 weeks, calculated by the product-limit method (Kaplan-Meier estimate) which took into account censored data. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description:
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Overall Number of Participants Analyzed 7 26 20 47 47 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants with PFS
100
(100 to 100)
72.9
(49.3 to 86.8)
54.9
(29.4 to 74.6)
55.6
(40.0 to 68.6)
63.8
(48.4 to 75.7)
NA [1] 
(NA to NA)
[1]
PFS rate at 24 weeks was not calculated for this arm
6.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time from the date of first dose of study medication to the date of first disease progression or death. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
Time Frame From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm S: SUN + NIV2 Arm S: SUN + NIV5 Arm P: PAZ + NIV2 Arm I-1: IPI1 + NIV3 Arm I-3: IPI3 + NIV1 Arm IN-3: IPI3 + NIV3
Hide Arm/Group Description:
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Overall Number of Participants Analyzed 7 26 20 47 47 6
Median (95% Confidence Interval)
Unit of Measure: months
11.3 [1] 
(7.62 to NA)
12.7
(5.55 to 19.38)
7.2
(2.79 to 11.07)
7.7
(3.71 to 14.29)
9.4
(5.62 to 18.63)
8.5 [1] 
(1.31 to NA)
[1]
Upper 95% CI not reached
Time Frame From first dose to date of last dose plus 100 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SUNITINIB+NIVOLUMAB PAZOPANIB+NIVOLUMAB NIVO 3+IPI 1 (MG/KG) NIVO 1+IPI 3 (MG/KG) NIVO 3+IPI 3 (MG/KG)
Hide Arm/Group Description Nivolumab (2mg/kg or 5mg/kg)administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses.

Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

All-Cause Mortality
SUNITINIB+NIVOLUMAB PAZOPANIB+NIVOLUMAB NIVO 3+IPI 1 (MG/KG) NIVO 1+IPI 3 (MG/KG) NIVO 3+IPI 3 (MG/KG)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
SUNITINIB+NIVOLUMAB PAZOPANIB+NIVOLUMAB NIVO 3+IPI 1 (MG/KG) NIVO 1+IPI 3 (MG/KG) NIVO 3+IPI 3 (MG/KG)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/33 (57.58%)   13/20 (65.00%)   29/47 (61.70%)   30/47 (63.83%)   4/6 (66.67%) 
Blood and lymphatic system disorders           
Methaemoglobinaemia  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Thrombocytopenia  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Lymphadenopathy  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Cardiac disorders           
Myocardial ischaemia  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Sinus tachycardia  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Atrial fibrillation  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Endocrine disorders           
Adrenal insufficiency  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Hyperthyroidism  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Hypophysitis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Hypopituitarism  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Eye disorders           
Diplopia  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders           
Abdominal pain  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Autoimmune colitis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Colitis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  6/47 (12.77%)  0/6 (0.00%) 
Diarrhoea  1  2/33 (6.06%)  2/20 (10.00%)  4/47 (8.51%)  6/47 (12.77%)  1/6 (16.67%) 
Duodenitis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Erosive duodenitis  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Gastritis erosive  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Large intestinal obstruction  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Nausea  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Small intestinal obstruction  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Vomiting  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Gastric haemorrhage  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
General disorders           
Chills  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Hernia  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Mucosal ulceration  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Pain  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  4/47 (8.51%)  0/6 (0.00%) 
Pyrexia  1  1/33 (3.03%)  2/20 (10.00%)  4/47 (8.51%)  3/47 (6.38%)  2/6 (33.33%) 
Sudden death  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Systemic inflammatory response syndrome  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
Hepatobiliary disorders           
Autoimmune hepatitis  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Cholangitis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Drug-induced liver injury  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Hepatitis acute  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Infections and infestations           
Appendicitis perforated  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Bacteraemia  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Enterocolitis infectious  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Gastroenteritis  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Gastroenteritis viral  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Lung infection  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  1/6 (16.67%) 
Pneumonia  1  1/33 (3.03%)  2/20 (10.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Pneumonia legionella  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Skin infection  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Viral infection  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Localised infection  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Pneumocystis jirovecii pneumonia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications           
Ankle fracture  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Fracture  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Spinal fracture  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  4/47 (8.51%)  0/6 (0.00%) 
Aspartate aminotransferase increased  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  4/47 (8.51%)  0/6 (0.00%) 
Blood bilirubin increased  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Blood creatinine increased  1  0/33 (0.00%)  1/20 (5.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Lipase increased  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Platelet count decreased  1  1/33 (3.03%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Transaminases increased  1  1/33 (3.03%)  0/20 (0.00%)  1/47 (2.13%)  2/47 (4.26%)  0/6 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  2/33 (6.06%)  2/20 (10.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Diabetic ketoacidosis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Hypercalcaemia  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Hyponatraemia  1  3/33 (9.09%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Hyperkalaemia  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Back pain  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Muscular weakness  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Musculoskeletal pain  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Neck pain  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Musculoskeletal chest pain  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Pain in extremity  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Malignant ascites  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Malignant neoplasm progression  1  1/33 (3.03%)  2/20 (10.00%)  6/47 (12.77%)  2/47 (4.26%)  1/6 (16.67%) 
Metastases to bone  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Tumour flare  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Metastases to central nervous system  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Nervous system disorders           
Balance disorder  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Headache  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Neuropathy peripheral  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Peripheral motor neuropathy  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Seizure  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Spinal cord compression  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Syncope  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Transient global amnesia  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Transient ischaemic attack  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Haemorrhage intracranial  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Posterior reversible encephalopathy syndrome  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Renal and urinary disorders           
Acute kidney injury  1  3/33 (9.09%)  0/20 (0.00%)  3/47 (6.38%)  1/47 (2.13%)  0/6 (0.00%) 
Renal failure  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Atelectasis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Cough  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Dyspnoea  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  4/47 (8.51%)  0/6 (0.00%) 
Haemoptysis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Hypoxia  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Pleural effusion  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Pneumonitis  1  1/33 (3.03%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Pulmonary embolism  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders           
Rash maculo-papular  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Vascular disorders           
Haemorrhage  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Hypertension  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Hypotension  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Orthostatic hypotension  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Thrombosis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SUNITINIB+NIVOLUMAB PAZOPANIB+NIVOLUMAB NIVO 3+IPI 1 (MG/KG) NIVO 1+IPI 3 (MG/KG) NIVO 3+IPI 3 (MG/KG)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/33 (100.00%)   20/20 (100.00%)   47/47 (100.00%)   46/47 (97.87%)   6/6 (100.00%) 
Blood and lymphatic system disorders           
Anaemia  1  8/33 (24.24%)  3/20 (15.00%)  7/47 (14.89%)  10/47 (21.28%)  1/6 (16.67%) 
Leukopenia  1  3/33 (9.09%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Neutropenia  1  5/33 (15.15%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Thrombocytopenia  1  4/33 (12.12%)  0/20 (0.00%)  2/47 (4.26%)  2/47 (4.26%)  1/6 (16.67%) 
Cardiac disorders           
Atrial fibrillation  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  2/47 (4.26%)  0/6 (0.00%) 
Bradycardia  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  2/47 (4.26%)  1/6 (16.67%) 
Left ventricular dysfunction  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Palpitations  1  1/33 (3.03%)  1/20 (5.00%)  6/47 (12.77%)  3/47 (6.38%)  1/6 (16.67%) 
Tachycardia  1  1/33 (3.03%)  0/20 (0.00%)  5/47 (10.64%)  2/47 (4.26%)  1/6 (16.67%) 
Ear and labyrinth disorders           
Ear congestion  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Tinnitus  1  1/33 (3.03%)  2/20 (10.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Vertigo  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
Endocrine disorders           
Adrenal insufficiency  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  6/47 (12.77%)  2/6 (33.33%) 
Autoimmune thyroiditis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Cushingoid  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Endocrine disorder  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Hyperthyroidism  1  5/33 (15.15%)  0/20 (0.00%)  3/47 (6.38%)  8/47 (17.02%)  3/6 (50.00%) 
Hypothyroidism  1  10/33 (30.30%)  4/20 (20.00%)  10/47 (21.28%)  13/47 (27.66%)  5/6 (83.33%) 
Lymphocytic hypophysitis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Autoimmune hypothyroidism  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Eye disorders           
Dry eye  1  2/33 (6.06%)  0/20 (0.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Eye pain  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
Lacrimation increased  1  4/33 (12.12%)  0/20 (0.00%)  3/47 (6.38%)  5/47 (10.64%)  1/6 (16.67%) 
Ocular hyperaemia  1  1/33 (3.03%)  0/20 (0.00%)  1/47 (2.13%)  2/47 (4.26%)  1/6 (16.67%) 
Periorbital oedema  1  5/33 (15.15%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Photopsia  1  0/33 (0.00%)  2/20 (10.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Vision blurred  1  2/33 (6.06%)  1/20 (5.00%)  6/47 (12.77%)  5/47 (10.64%)  1/6 (16.67%) 
Visual impairment  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Vitreous detachment  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Vitreous floaters  1  2/33 (6.06%)  2/20 (10.00%)  2/47 (4.26%)  0/47 (0.00%)  1/6 (16.67%) 
Vitreous haemorrhage  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders           
Abdominal distension  1  3/33 (9.09%)  4/20 (20.00%)  4/47 (8.51%)  5/47 (10.64%)  1/6 (16.67%) 
Abdominal pain  1  5/33 (15.15%)  7/20 (35.00%)  10/47 (21.28%)  12/47 (25.53%)  2/6 (33.33%) 
Abdominal pain lower  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Abdominal pain upper  1  3/33 (9.09%)  2/20 (10.00%)  4/47 (8.51%)  3/47 (6.38%)  1/6 (16.67%) 
Anal inflammation  1  2/33 (6.06%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Ascites  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Autoimmune colitis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Breath odour  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Colitis  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  1/47 (2.13%)  1/6 (16.67%) 
Constipation  1  9/33 (27.27%)  8/20 (40.00%)  14/47 (29.79%)  14/47 (29.79%)  2/6 (33.33%) 
Defaecation urgency  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Dental caries  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Diarrhoea  1  21/33 (63.64%)  14/20 (70.00%)  12/47 (25.53%)  25/47 (53.19%)  5/6 (83.33%) 
Dry mouth  1  11/33 (33.33%)  2/20 (10.00%)  5/47 (10.64%)  8/47 (17.02%)  1/6 (16.67%) 
Duodenitis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Dyspepsia  1  11/33 (33.33%)  5/20 (25.00%)  6/47 (12.77%)  1/47 (2.13%)  2/6 (33.33%) 
Dysphagia  1  2/33 (6.06%)  3/20 (15.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Flatulence  1  6/33 (18.18%)  1/20 (5.00%)  5/47 (10.64%)  3/47 (6.38%)  2/6 (33.33%) 
Gastritis  1  3/33 (9.09%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Gastrooesophageal reflux disease  1  9/33 (27.27%)  3/20 (15.00%)  4/47 (8.51%)  1/47 (2.13%)  0/6 (0.00%) 
Glossodynia  1  4/33 (12.12%)  0/20 (0.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Haematochezia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Haemorrhoids  1  1/33 (3.03%)  0/20 (0.00%)  2/47 (4.26%)  3/47 (6.38%)  0/6 (0.00%) 
Mouth ulceration  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Nausea  1  20/33 (60.61%)  16/20 (80.00%)  19/47 (40.43%)  26/47 (55.32%)  4/6 (66.67%) 
Oral pain  1  5/33 (15.15%)  4/20 (20.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Paraesthesia oral  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Stomatitis  1  8/33 (24.24%)  2/20 (10.00%)  7/47 (14.89%)  0/47 (0.00%)  2/6 (33.33%) 
Toothache  1  2/33 (6.06%)  2/20 (10.00%)  3/47 (6.38%)  2/47 (4.26%)  0/6 (0.00%) 
Vomiting  1  10/33 (30.30%)  9/20 (45.00%)  15/47 (31.91%)  14/47 (29.79%)  3/6 (50.00%) 
Retching  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
General disorders           
Asthenia  1  0/33 (0.00%)  1/20 (5.00%)  3/47 (6.38%)  4/47 (8.51%)  1/6 (16.67%) 
Chest discomfort  1  3/33 (9.09%)  2/20 (10.00%)  2/47 (4.26%)  2/47 (4.26%)  0/6 (0.00%) 
Chest pain  1  0/33 (0.00%)  3/20 (15.00%)  5/47 (10.64%)  1/47 (2.13%)  1/6 (16.67%) 
Chills  1  8/33 (24.24%)  6/20 (30.00%)  13/47 (27.66%)  9/47 (19.15%)  3/6 (50.00%) 
Face oedema  1  4/33 (12.12%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  1/6 (16.67%) 
Fatigue  1  29/33 (87.88%)  15/20 (75.00%)  31/47 (65.96%)  35/47 (74.47%)  6/6 (100.00%) 
Generalised oedema  1  2/33 (6.06%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Influenza like illness  1  3/33 (9.09%)  0/20 (0.00%)  2/47 (4.26%)  2/47 (4.26%)  0/6 (0.00%) 
Localised oedema  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Malaise  1  2/33 (6.06%)  2/20 (10.00%)  1/47 (2.13%)  1/47 (2.13%)  1/6 (16.67%) 
Mucosal inflammation  1  11/33 (33.33%)  5/20 (25.00%)  2/47 (4.26%)  4/47 (8.51%)  1/6 (16.67%) 
Non-cardiac chest pain  1  1/33 (3.03%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  1/6 (16.67%) 
Oedema  1  1/33 (3.03%)  1/20 (5.00%)  2/47 (4.26%)  1/47 (2.13%)  1/6 (16.67%) 
Oedema peripheral  1  11/33 (33.33%)  5/20 (25.00%)  12/47 (25.53%)  13/47 (27.66%)  3/6 (50.00%) 
Pain  1  0/33 (0.00%)  2/20 (10.00%)  2/47 (4.26%)  2/47 (4.26%)  1/6 (16.67%) 
Pyrexia  1  10/33 (30.30%)  7/20 (35.00%)  18/47 (38.30%)  11/47 (23.40%)  6/6 (100.00%) 
Sensation of foreign body  1  2/33 (6.06%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Temperature intolerance  1  2/33 (6.06%)  1/20 (5.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders           
Autoimmune hepatitis  1  0/33 (0.00%)  1/20 (5.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Immune system disorders           
Anaphylactic reaction  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Infections and infestations           
Bronchitis  1  3/33 (9.09%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Clostridium difficile infection  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Ear infection  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Gingivitis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Groin abscess  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Infected bite  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Lung infection  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Pneumonia  1  1/33 (3.03%)  2/20 (10.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Post procedural infection  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Rhinitis  1  2/33 (6.06%)  1/20 (5.00%)  1/47 (2.13%)  2/47 (4.26%)  1/6 (16.67%) 
Sinusitis  1  1/33 (3.03%)  1/20 (5.00%)  4/47 (8.51%)  3/47 (6.38%)  0/6 (0.00%) 
Skin infection  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Tinea infection  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Tooth infection  1  3/33 (9.09%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Upper respiratory tract infection  1  8/33 (24.24%)  7/20 (35.00%)  9/47 (19.15%)  7/47 (14.89%)  0/6 (0.00%) 
Urinary tract infection  1  1/33 (3.03%)  2/20 (10.00%)  2/47 (4.26%)  3/47 (6.38%)  2/6 (33.33%) 
Vulvitis  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  1/6 (16.67%) 
Cellulitis  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Genital infection fungal  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Pharyngitis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Injury, poisoning and procedural complications           
Ankle fracture  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
Contusion  1  5/33 (15.15%)  0/20 (0.00%)  2/47 (4.26%)  3/47 (6.38%)  0/6 (0.00%) 
Fall  1  1/33 (3.03%)  1/20 (5.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Fracture  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Infusion related reaction  1  0/33 (0.00%)  1/20 (5.00%)  5/47 (10.64%)  1/47 (2.13%)  1/6 (16.67%) 
Laceration  1  0/33 (0.00%)  0/20 (0.00%)  3/47 (6.38%)  0/47 (0.00%)  0/6 (0.00%) 
Post procedural complication  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Procedural pain  1  0/33 (0.00%)  3/20 (15.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Skin abrasion  1  2/33 (6.06%)  1/20 (5.00%)  3/47 (6.38%)  3/47 (6.38%)  0/6 (0.00%) 
Sunburn  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  13/33 (39.39%)  5/20 (25.00%)  8/47 (17.02%)  16/47 (34.04%)  3/6 (50.00%) 
Amylase increased  1  5/33 (15.15%)  0/20 (0.00%)  4/47 (8.51%)  8/47 (17.02%)  2/6 (33.33%) 
Aspartate aminotransferase increased  1  12/33 (36.36%)  6/20 (30.00%)  9/47 (19.15%)  14/47 (29.79%)  3/6 (50.00%) 
Blood alkaline phosphatase increased  1  5/33 (15.15%)  3/20 (15.00%)  2/47 (4.26%)  4/47 (8.51%)  0/6 (0.00%) 
Blood bilirubin increased  1  1/33 (3.03%)  0/20 (0.00%)  2/47 (4.26%)  3/47 (6.38%)  1/6 (16.67%) 
Blood cholesterol increased  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Blood creatinine increased  1  12/33 (36.36%)  2/20 (10.00%)  7/47 (14.89%)  9/47 (19.15%)  2/6 (33.33%) 
Gamma-glutamyltransferase increased  1  2/33 (6.06%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Lipase increased  1  2/33 (6.06%)  0/20 (0.00%)  11/47 (23.40%)  19/47 (40.43%)  2/6 (33.33%) 
Lymphocyte count decreased  1  9/33 (27.27%)  1/20 (5.00%)  1/47 (2.13%)  4/47 (8.51%)  1/6 (16.67%) 
Neutrophil count decreased  1  6/33 (18.18%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Platelet count decreased  1  6/33 (18.18%)  0/20 (0.00%)  3/47 (6.38%)  0/47 (0.00%)  0/6 (0.00%) 
Weight decreased  1  4/33 (12.12%)  4/20 (20.00%)  5/47 (10.64%)  11/47 (23.40%)  4/6 (66.67%) 
Weight increased  1  3/33 (9.09%)  0/20 (0.00%)  7/47 (14.89%)  4/47 (8.51%)  1/6 (16.67%) 
White blood cell count decreased  1  7/33 (21.21%)  1/20 (5.00%)  1/47 (2.13%)  2/47 (4.26%)  0/6 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  16/33 (48.48%)  11/20 (55.00%)  13/47 (27.66%)  19/47 (40.43%)  5/6 (83.33%) 
Dehydration  1  7/33 (21.21%)  6/20 (30.00%)  7/47 (14.89%)  9/47 (19.15%)  1/6 (16.67%) 
Diabetes mellitus  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Gout  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Hypercalcaemia  1  0/33 (0.00%)  2/20 (10.00%)  4/47 (8.51%)  5/47 (10.64%)  1/6 (16.67%) 
Hyperglycaemia  1  8/33 (24.24%)  4/20 (20.00%)  7/47 (14.89%)  8/47 (17.02%)  1/6 (16.67%) 
Hyperkalaemia  1  3/33 (9.09%)  2/20 (10.00%)  5/47 (10.64%)  4/47 (8.51%)  0/6 (0.00%) 
Hyperphosphataemia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Hyperuricaemia  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Hypoalbuminaemia  1  3/33 (9.09%)  0/20 (0.00%)  1/47 (2.13%)  5/47 (10.64%)  2/6 (33.33%) 
Hypocalcaemia  1  3/33 (9.09%)  2/20 (10.00%)  1/47 (2.13%)  4/47 (8.51%)  1/6 (16.67%) 
Hypoglycaemia  1  0/33 (0.00%)  2/20 (10.00%)  0/47 (0.00%)  3/47 (6.38%)  0/6 (0.00%) 
Hypokalaemia  1  1/33 (3.03%)  1/20 (5.00%)  3/47 (6.38%)  4/47 (8.51%)  1/6 (16.67%) 
Hypomagnesaemia  1  3/33 (9.09%)  5/20 (25.00%)  3/47 (6.38%)  6/47 (12.77%)  1/6 (16.67%) 
Hyponatraemia  1  9/33 (27.27%)  1/20 (5.00%)  6/47 (12.77%)  6/47 (12.77%)  1/6 (16.67%) 
Hypophagia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Hypophosphataemia  1  3/33 (9.09%)  2/20 (10.00%)  3/47 (6.38%)  6/47 (12.77%)  0/6 (0.00%) 
Polydipsia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  12/33 (36.36%)  9/20 (45.00%)  24/47 (51.06%)  12/47 (25.53%)  5/6 (83.33%) 
Arthritis  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
Back pain  1  7/33 (21.21%)  6/20 (30.00%)  15/47 (31.91%)  8/47 (17.02%)  1/6 (16.67%) 
Costochondritis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Flank pain  1  1/33 (3.03%)  2/20 (10.00%)  8/47 (17.02%)  1/47 (2.13%)  0/6 (0.00%) 
Joint range of motion decreased  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Joint swelling  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  2/47 (4.26%)  1/6 (16.67%) 
Lower extremity mass  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Muscle spasms  1  4/33 (12.12%)  5/20 (25.00%)  3/47 (6.38%)  4/47 (8.51%)  3/6 (50.00%) 
Muscle twitching  1  0/33 (0.00%)  2/20 (10.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Muscular weakness  1  2/33 (6.06%)  2/20 (10.00%)  3/47 (6.38%)  6/47 (12.77%)  2/6 (33.33%) 
Musculoskeletal chest pain  1  2/33 (6.06%)  5/20 (25.00%)  6/47 (12.77%)  1/47 (2.13%)  0/6 (0.00%) 
Musculoskeletal pain  1  2/33 (6.06%)  4/20 (20.00%)  3/47 (6.38%)  5/47 (10.64%)  2/6 (33.33%) 
Musculoskeletal stiffness  1  2/33 (6.06%)  0/20 (0.00%)  1/47 (2.13%)  4/47 (8.51%)  0/6 (0.00%) 
Myalgia  1  10/33 (30.30%)  5/20 (25.00%)  11/47 (23.40%)  10/47 (21.28%)  4/6 (66.67%) 
Neck pain  1  0/33 (0.00%)  2/20 (10.00%)  8/47 (17.02%)  0/47 (0.00%)  0/6 (0.00%) 
Osteoarthritis  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  1/6 (16.67%) 
Osteonecrosis of jaw  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Pain in extremity  1  12/33 (36.36%)  6/20 (30.00%)  8/47 (17.02%)  5/47 (10.64%)  2/6 (33.33%) 
Pain in jaw  1  1/33 (3.03%)  1/20 (5.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Myopathy  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Nervous system disorders           
Ataxia  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Carpal tunnel syndrome  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Cerebellar syndrome  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Cognitive disorder  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  3/47 (6.38%)  1/6 (16.67%) 
Disturbance in attention  1  2/33 (6.06%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Dizziness  1  11/33 (33.33%)  3/20 (15.00%)  10/47 (21.28%)  12/47 (25.53%)  2/6 (33.33%) 
Dysgeusia  1  21/33 (63.64%)  10/20 (50.00%)  5/47 (10.64%)  8/47 (17.02%)  1/6 (16.67%) 
Epilepsy  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Headache  1  13/33 (39.39%)  5/20 (25.00%)  15/47 (31.91%)  13/47 (27.66%)  4/6 (66.67%) 
Hyperaesthesia  1  1/33 (3.03%)  2/20 (10.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Neuropathy peripheral  1  4/33 (12.12%)  2/20 (10.00%)  1/47 (2.13%)  3/47 (6.38%)  0/6 (0.00%) 
Paraesthesia  1  1/33 (3.03%)  1/20 (5.00%)  4/47 (8.51%)  3/47 (6.38%)  2/6 (33.33%) 
Peripheral sensory neuropathy  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  3/47 (6.38%)  0/6 (0.00%) 
Restless legs syndrome  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Sciatica  1  0/33 (0.00%)  0/20 (0.00%)  1/47 (2.13%)  3/47 (6.38%)  1/6 (16.67%) 
Seizure  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Somnolence  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Speech disorder  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Syncope  1  1/33 (3.03%)  1/20 (5.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Tremor  1  0/33 (0.00%)  1/20 (5.00%)  3/47 (6.38%)  2/47 (4.26%)  2/6 (33.33%) 
Psychiatric disorders           
Anxiety  1  3/33 (9.09%)  2/20 (10.00%)  7/47 (14.89%)  4/47 (8.51%)  1/6 (16.67%) 
Confusional state  1  2/33 (6.06%)  0/20 (0.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Depression  1  4/33 (12.12%)  0/20 (0.00%)  1/47 (2.13%)  2/47 (4.26%)  2/6 (33.33%) 
Insomnia  1  5/33 (15.15%)  4/20 (20.00%)  9/47 (19.15%)  9/47 (19.15%)  3/6 (50.00%) 
Irritability  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  3/47 (6.38%)  1/6 (16.67%) 
Mental status changes  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  1/6 (16.67%) 
Libido decreased  1  2/33 (6.06%)  0/20 (0.00%)  0/47 (0.00%)  2/47 (4.26%)  0/6 (0.00%) 
Renal and urinary disorders           
Acute kidney injury  1  3/33 (9.09%)  1/20 (5.00%)  1/47 (2.13%)  2/47 (4.26%)  1/6 (16.67%) 
Azotaemia  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Haematuria  1  1/33 (3.03%)  2/20 (10.00%)  1/47 (2.13%)  2/47 (4.26%)  1/6 (16.67%) 
Nocturia  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  3/47 (6.38%)  0/6 (0.00%) 
Pollakiuria  1  1/33 (3.03%)  2/20 (10.00%)  1/47 (2.13%)  2/47 (4.26%)  0/6 (0.00%) 
Polyuria  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Proteinuria  1  4/33 (12.12%)  1/20 (5.00%)  3/47 (6.38%)  6/47 (12.77%)  2/6 (33.33%) 
Urinary retention  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Reproductive system and breast disorders           
Breast mass  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Erectile dysfunction  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Testicular pain  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  18/33 (54.55%)  13/20 (65.00%)  24/47 (51.06%)  14/47 (29.79%)  5/6 (83.33%) 
Dysphonia  1  4/33 (12.12%)  5/20 (25.00%)  7/47 (14.89%)  4/47 (8.51%)  1/6 (16.67%) 
Dyspnoea  1  12/33 (36.36%)  4/20 (20.00%)  13/47 (27.66%)  9/47 (19.15%)  2/6 (33.33%) 
Dyspnoea at rest  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Dyspnoea exertional  1  4/33 (12.12%)  3/20 (15.00%)  7/47 (14.89%)  4/47 (8.51%)  0/6 (0.00%) 
Epistaxis  1  6/33 (18.18%)  2/20 (10.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Haemoptysis  1  2/33 (6.06%)  2/20 (10.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Hiccups  1  0/33 (0.00%)  1/20 (5.00%)  3/47 (6.38%)  1/47 (2.13%)  0/6 (0.00%) 
Hypoxia  1  1/33 (3.03%)  0/20 (0.00%)  3/47 (6.38%)  2/47 (4.26%)  1/6 (16.67%) 
Nasal congestion  1  8/33 (24.24%)  1/20 (5.00%)  9/47 (19.15%)  6/47 (12.77%)  1/6 (16.67%) 
Nasal dryness  1  3/33 (9.09%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Oropharyngeal pain  1  8/33 (24.24%)  3/20 (15.00%)  6/47 (12.77%)  5/47 (10.64%)  0/6 (0.00%) 
Paranasal sinus hypersecretion  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Pharyngeal inflammation  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Pleural effusion  1  1/33 (3.03%)  0/20 (0.00%)  4/47 (8.51%)  0/47 (0.00%)  0/6 (0.00%) 
Pleuritic pain  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Pneumonitis  1  2/33 (6.06%)  1/20 (5.00%)  3/47 (6.38%)  5/47 (10.64%)  0/6 (0.00%) 
Productive cough  1  0/33 (0.00%)  0/20 (0.00%)  2/47 (4.26%)  3/47 (6.38%)  1/6 (16.67%) 
Pulmonary embolism  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Respiratory tract congestion  1  2/33 (6.06%)  0/20 (0.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Rhinitis allergic  1  5/33 (15.15%)  1/20 (5.00%)  8/47 (17.02%)  0/47 (0.00%)  0/6 (0.00%) 
Rhinorrhoea  1  1/33 (3.03%)  1/20 (5.00%)  1/47 (2.13%)  2/47 (4.26%)  0/6 (0.00%) 
Sinus congestion  1  1/33 (3.03%)  1/20 (5.00%)  4/47 (8.51%)  2/47 (4.26%)  0/6 (0.00%) 
Sleep apnoea syndrome  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Sneezing  1  2/33 (6.06%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  0/6 (0.00%) 
Throat irritation  1  0/33 (0.00%)  1/20 (5.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Upper-airway cough syndrome  1  1/33 (3.03%)  1/20 (5.00%)  2/47 (4.26%)  2/47 (4.26%)  0/6 (0.00%) 
Wheezing  1  1/33 (3.03%)  0/20 (0.00%)  7/47 (14.89%)  2/47 (4.26%)  0/6 (0.00%) 
Sputum increased  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  1/33 (3.03%)  2/20 (10.00%)  2/47 (4.26%)  1/47 (2.13%)  0/6 (0.00%) 
Blister  1  2/33 (6.06%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Dermatitis acneiform  1  1/33 (3.03%)  1/20 (5.00%)  3/47 (6.38%)  0/47 (0.00%)  0/6 (0.00%) 
Dry skin  1  11/33 (33.33%)  3/20 (15.00%)  11/47 (23.40%)  4/47 (8.51%)  1/6 (16.67%) 
Dyshidrotic eczema  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Ecchymosis  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Erythema  1  3/33 (9.09%)  2/20 (10.00%)  2/47 (4.26%)  4/47 (8.51%)  1/6 (16.67%) 
Hair colour changes  1  6/33 (18.18%)  4/20 (20.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Hair growth abnormal  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Hyperhidrosis  1  1/33 (3.03%)  2/20 (10.00%)  5/47 (10.64%)  2/47 (4.26%)  3/6 (50.00%) 
Hyperkeratosis  1  2/33 (6.06%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Night sweats  1  0/33 (0.00%)  1/20 (5.00%)  3/47 (6.38%)  4/47 (8.51%)  2/6 (33.33%) 
Palmar-plantar erythrodysaesthesia syndrome  1  13/33 (39.39%)  0/20 (0.00%)  1/47 (2.13%)  1/47 (2.13%)  1/6 (16.67%) 
Pruritus  1  9/33 (27.27%)  9/20 (45.00%)  18/47 (38.30%)  21/47 (44.68%)  3/6 (50.00%) 
Pruritus generalised  1  0/33 (0.00%)  1/20 (5.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Psoriasis  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Purpura  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Rash  1  9/33 (27.27%)  7/20 (35.00%)  18/47 (38.30%)  15/47 (31.91%)  4/6 (66.67%) 
Rash generalised  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Rash macular  1  0/33 (0.00%)  0/20 (0.00%)  3/47 (6.38%)  2/47 (4.26%)  0/6 (0.00%) 
Rash maculo-papular  1  10/33 (30.30%)  4/20 (20.00%)  7/47 (14.89%)  8/47 (17.02%)  0/6 (0.00%) 
Rash papular  1  0/33 (0.00%)  1/20 (5.00%)  2/47 (4.26%)  0/47 (0.00%)  0/6 (0.00%) 
Rash pruritic  1  0/33 (0.00%)  1/20 (5.00%)  2/47 (4.26%)  4/47 (8.51%)  0/6 (0.00%) 
Skin discolouration  1  3/33 (9.09%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Skin disorder  1  2/33 (6.06%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Skin exfoliation  1  2/33 (6.06%)  2/20 (10.00%)  2/47 (4.26%)  1/47 (2.13%)  1/6 (16.67%) 
Skin hyperpigmentation  1  1/33 (3.03%)  0/20 (0.00%)  0/47 (0.00%)  1/47 (2.13%)  1/6 (16.67%) 
Skin lesion  1  1/33 (3.03%)  1/20 (5.00%)  2/47 (4.26%)  2/47 (4.26%)  1/6 (16.67%) 
Skin mass  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Urticaria  1  0/33 (0.00%)  1/20 (5.00%)  3/47 (6.38%)  0/47 (0.00%)  0/6 (0.00%) 
Yellow skin  1  7/33 (21.21%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Vascular disorders           
Deep vein thrombosis  1  2/33 (6.06%)  0/20 (0.00%)  1/47 (2.13%)  0/47 (0.00%)  0/6 (0.00%) 
Flushing  1  5/33 (15.15%)  3/20 (15.00%)  3/47 (6.38%)  6/47 (12.77%)  1/6 (16.67%) 
Haematoma  1  1/33 (3.03%)  1/20 (5.00%)  0/47 (0.00%)  1/47 (2.13%)  0/6 (0.00%) 
Hot flush  1  5/33 (15.15%)  2/20 (10.00%)  3/47 (6.38%)  4/47 (8.51%)  0/6 (0.00%) 
Hypertension  1  17/33 (51.52%)  8/20 (40.00%)  4/47 (8.51%)  6/47 (12.77%)  3/6 (50.00%) 
Hypotension  1  2/33 (6.06%)  4/20 (20.00%)  3/47 (6.38%)  6/47 (12.77%)  2/6 (33.33%) 
Orthostatic hypertension  1  0/33 (0.00%)  1/20 (5.00%)  0/47 (0.00%)  0/47 (0.00%)  0/6 (0.00%) 
Phlebitis  1  0/33 (0.00%)  0/20 (0.00%)  0/47 (0.00%)  0/47 (0.00%)  1/6 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
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Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01472081    
Other Study ID Numbers: CA209-016
First Submitted: October 26, 2011
First Posted: November 16, 2011
Results First Submitted: May 23, 2018
Results First Posted: August 2, 2019
Last Update Posted: April 22, 2020