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Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

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ClinicalTrials.gov Identifier: NCT01668784
Recruitment Status : Active, not recruiting
First Posted : August 20, 2012
Results First Posted : April 29, 2016
Last Update Posted : August 9, 2019
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
Interventions Biological: Nivolumab
Drug: Everolimus
Enrollment 1068
Recruitment Details  
Pre-assignment Details 1054 participants enrolled, 821 participants randomized (410 nivolumab, 411 everolimus). Reasons for non-randomization include 9 participants had adverse events, 15 participants withdrew consent, 2 participants died, 1 participant lost to follow-up, 193 participants no longer met study criteria, and 13 participants for other non-listed reasons.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Period Title: Randomized (Pre-treatment)
Started 410 411
Completed 406 397
Not Completed 4 14
Reason Not Completed
Disease Progression             0             1
Request to Discontinue Study Treatment             0             3
Withdrawal by Subject             1             8
Poor/Non-Compliance             1             0
No Longer Meets Study Criteria             2             1
Not Specified             0             1
Period Title: Treated (Overall)
Started 406 397
Completed 67 28
Not Completed 339 369
Reason Not Completed
Disease Progression             285             273
Study Drug Toxicity             35             53
Death             1             1
Adverse Event Unrelated to Study Drug             9             14
Request to Discontinue Study Treatment             5             18
Withdrawal by Subject             2             3
Maximal Clinical Benefit             2             3
Not Specified             0             4
Arm/Group Title Nivolumab Everolimus Total
Hide Arm/Group Description Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Total of all reporting groups
Overall Number of Baseline Participants 410 411 821
Hide Baseline Analysis Population Description
All randomized participants; any participants that was randomized to any treatment group in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 410 participants 411 participants 821 participants
60.6  (10.87) 61.9  (10.43) 61.3  (10.66)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
< 65 years 257 240 497
>= 65 and < 75 119 131 250
>= 75 years 34 40 74
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
Female
95
  23.2%
107
  26.0%
202
  24.6%
Male
315
  76.8%
304
  74.0%
619
  75.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
White 353 367 720
Black or African American 1 4 5
Asian 42 32 74
American Indian or Alaska Native 1 0 1
Native Hawaiian or Other Pacific Islander 0 1 1
Other 13 7 20
Baseline MSKCC Risk Group (IVRS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
Favorable 145 148 293
Intermediate 201 203 404
Poor 64 60 124
[1]
Measure Description: A prognostic model used to assess pretreatment clinical features that are predictive of survival. The Memorial Sloan-Kettering Cancer Center (MSKCC) risk system stratifies patients into poor-, intermediate- and favorable-risk categories based on the number of adverse clinical and laboratory parameters present. An Interactive Voice Response System (IVRS) was used to record responses.
Region  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
US/Canada 174 172 346
Western Europe 140 141 281
Rest of World (ROW) 96 98 194
Number of Prior Anti-Angiogenic Agents Received in the Advanced/Metastatic Setting  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
1 294 297 591
2 116 114 230
PD-L1 Expression  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 410 participants 411 participants 821 participants
PD-L1 Quantifiable >=1% 94 87 181
PD-L1 Quantifiable <1% 276 299 575
PD-L1 Indeterminate/Not Evaluable 40 25 65
1.Primary Outcome
Title Overall Survival (OS) at Primary Endpoint
Hide Description

Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p < 0.0148) was crossed while no new safety signals that would affect continuation of the study were found.

The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria.

Time Frame Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; any participants that was randomized to any treatment group in the study.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 410 411
Median (95% Confidence Interval)
Unit of Measure: months
25.00 [1] 
(21.75 to NA)
19.55
(17.64 to 23.06)
[1]
N.A.: Not Available: Too few events to estimate the upper limit of the confidence interval
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Everolimus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments The boundary for statistical significance required the p-value to be less than 0.0148 at the interim analyses.
Method Log Rank
Comments Log-rank Test stratified by the Memorial Sloan-Kettering Cancer Center risk group, number of prior anti-angiogenic therapies, and the region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 98.52%
0.57 to 0.93
Estimation Comments Stratified Cox proportional hazard model. Hazard ratio (HR) was Nivolumab over Everolimus.
2.Secondary Outcome
Title Investigator-assessed Objective Response Rate (ORR) at Primary Endpoint
Hide Description ORR=number of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. 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, the baseline sum diameters used as reference. Tumor assessments began at 8 weeks following randomization and continued every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or death. CIs used Clopper and Pearson.
Time Frame At 8 weeks post randomization, every 8 weeks for 12 months, and every 12 weeks until date of disease progression or death, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; any participants that was randomized to any treatment group in the study.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 410 411
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
25.1
(21.0 to 29.6)
5.4
(3.4 to 8.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Everolimus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Two-sided p-value from Cochran-Mantel-Haenszel test for the comparison of the odds ratio of Nivolumab over Everolimus.
Method Cochran-Mantel-Haenszel
Comments CHM test stratified by the Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, number of prior anti-angiogenic therapies, and the region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.98
Confidence Interval (2-Sided) 95%
3.68 to 9.72
Estimation Comments Ratio of Nivolumab over Everolimus
3.Secondary Outcome
Title Investigator-assessed Duration of Objective Response at Primary Endpoint
Hide Description Duration of objective response is defined as the time from first response (complete response, CR or partial response, PR) to the date of the first documented tumor progression as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. For participants who neither progress nor die, the duration of objective response were censored at the same time they were censored for the primary definition. 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, the baseline sum diameters used as reference. Based on Kaplan-Meier Estimates.
Time Frame From date of first response to date of disease progression or death or censoring if no progression or death occurred, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a response; any participants that were randomized to any treatment group in the study and that had a response.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 103 22
Median (95% Confidence Interval)
Unit of Measure: months
11.99
(7.85 to 23.03)
11.99 [1] 
(6.44 to NA)
[1]
N.A.: Not Available: Too few events to estimate the upper limit of the confidence interval
4.Secondary Outcome
Title Investigator-assessed Time to Objective Response at Primary Endpoint
Hide Description Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). 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, the baseline sum diameters used as reference.
Time Frame Randomization to date of first response, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with a response; any participants that was randomized to any treatment group in the study and that had a response.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 103 22
Median (Full Range)
Unit of Measure: months
3.52
(1.4 to 24.8)
3.70
(1.5 to 11.2)
5.Secondary Outcome
Title Investigator-assessed Time of Progression-free Survival (PFS) at Primary Endpoint
Hide Description PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: >=20% increase in sum of target lesion diameters and sum must show absolute increase of >=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates.
Time Frame Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; any participants that was randomized to any treatment group in the study.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 410 411
Median (95% Confidence Interval)
Unit of Measure: months
4.60
(3.71 to 5.39)
4.44
(3.71 to 5.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Everolimus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1135
Comments [Not Specified]
Method Log Rank
Comments Log-rank Test stratified by the Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, number of prior anti-angiogenic therapies, and the region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.75 to 1.03
Estimation Comments Stratified Cox proportional hazard model. Hazard ratio is nivolumab over everolimus.
6.Secondary Outcome
Title Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level at Primary Endpoint
Hide Description Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H&E process before the tumor biopsy specimen was sent for evaluation or from H&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable.
Time Frame Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
PD-L1 quantifiable participants; All randomized participants with quantifiable PD-L1 expression at baseline
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 370 386
Median (95% Confidence Interval)
Unit of Measure: months
Participant PD-L1 expression >=1% (n=94, 87)
21.82
(16.46 to 28.06)
18.79
(11.86 to 19.91)
Participant PD-L1 expression <1% (n=276, 299)
27.37 [1] 
(21.39 to NA)
21.22
(17.71 to 26.22)
[1]
N.A.: Not Available: not enough participants observed with event
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab, Everolimus
Comments Unstratified hazard ratio for participants with quantifiable PD-L1 expression level >= 1 percent
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.53 to 1.17
Estimation Comments Hazard ratio is nivolumab over everolimus
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nivolumab, Everolimus
Comments Unstratified hazard ratio for participants with quantifiable PD-L1 expression level < 1 percent
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.60 to 0.97
Estimation Comments Hazard ratio is nivolumab over everolimus
7.Secondary Outcome
Title Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events at Primary Endpoint
Hide Description Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: 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.
Time Frame Day of first dose to 30 days post final dose, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants; all participants who received at least one dose of nivolumab or everolimus
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 406 397
Measure Type: Number
Unit of Measure: participants
Deaths 181 213
SAEs 194 173
Drug related SAEs 47 53
Drug related AEs 319 349
Discontinued due to Drug-related AEs 31 52
Discontinued due to AEs 72 82
8.Secondary Outcome
Title Percentage of Participants With Disease-related Symptom Progression (DRSP) at Primary Endpoint
Hide Description Disease-related symptom progression rate (DRSPR)=a decrease of two points in the Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) questionnaire relative to the participant's baseline FKSI-DRS score with no later increase above this threshold observed during the course of the study. The 9 items of the FKSI-DRS were summarized into a symptom scale ranging in score from 0 to 36, with 0 being the worst possible score and 36 being the best possible score. A single measure reporting a decrease of at least 2 units was considered disease-related symptom progression only if it was the last one available for the participant. In order to consider a questionnaire received as valid, over 50% of the items were to be completed. Calculated by the Clopper-Pearson method for each treatment group.
Time Frame Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants; any participants that was randomized to any treatment group in the study.
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 410 411
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Disease-related Symptom Progression Rate (DRSPR)
41.2
(35.7 to 46.9)
54.2
(48.8 to 59.6)
DRSPR Including Death and Investigator Progression
86.6
(82.3 to 90.2)
95.0
(92.2 to 97.1)
9.Secondary Outcome
Title Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests at Primary Endpoint
Hide Description Aspartate aminotransferase, AST. Alanine aminotransaminase, ALT. Total bilirubin, tBIL. Thyroid stimulating hormone, TSH. Upper limit of normal (ULN). Units per Liter (U/L). Results reported in International System of Units (SI).
Time Frame Day 1 to 30 days post last dose, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants who received at least one dose of nivolumab or everolimus and had at least one measureable on-treatment measurement of the corresponding laboratory parameters
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 401 377
Measure Type: Number
Unit of Measure: participants
ALT or AST > 3.0*ULN U/L (n=401,377) 28 14
ALT or AST > 5.0*ULN U/L (n=401,377) 16 6
ALT or AST > 10.0*ULN U/L (n=401,377) 7 1
ALT or AST > 20.0*ULN U/L (n=401,377) 2 0
tBIL > 2.0*ULN U/L (n=401,376) 6 2
ALT or AST>3.0*ULN, tBIL>2.0 ULN, 1day(n=401,376) 3 0
ALT or AST>3.0*ULN, tBIL>2.0 ULN,30day(n=401,376) 4 1
TSH > ULN (n=382, 361) 148 70
TSH < LLN (n=382, 361) 59 55
10.Secondary Outcome
Title Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Hide Description Common Terminology Criteria (CTC) version 4.0 in International System of Units (SI); Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Hematology parameters=Hemoglobin (Gr 3: < 8.0 g/dL), Platelet Count (Gr 3: 25.0 -< 50.0*10^9 c/L; Gr 4: < 25.0*10^9 c/L), Leukocyte Count (Gr 3: 1.0 -< 2.0*10^3 c/µL; Gr4: < 1.0*10^3 c/µL), Absolute Lymphocyte Count (Gr 3: 0.2 -< 0.5*10^3 c/µL; Gr 4: < 0.2*10^3 c/µL), Absolute Neutrophil Count (Gr 3: 0.5 - < 1.0*10^3 c/µL; Gr 4: < 0.5*10^3 c/µL). Liver Function parameters=Alkaline Phosphatase (Gr 3: > 5.0 - 20.0 U/L * ULN; Gr 4: > 20.0 U/L * ULN), AST (Gr 3: > 5.0 - 20.0 U/L * ULN; Gr 4: > 20.0 U/L * ULN), ALT (Gr 3: > 5.0 - 20.0 U/L * ULN; Gr 4: > 20.0 U/L * ULN), tBIL (Gr 3: > 3.0 - 10.0 mg/dL * ULN; Gr 4: > 10.0 mg/dL * ULN). Renal parameter=Creatinine (Grade: Gr3: > 3.0 - 6.0 mg/dL *ULN; Gr4: > 6.0 mg/dL *ULN). Cells per microliter (c/µL). Cells per Liter (c/L). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).
Time Frame Day 1 to 30 days post last dose, up to May 2015 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants; all participants who received at least one dose of nivolumab or everolimus and at least one measureable on-treatment measurement of the corresponding laboratory parameter
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description:
Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Overall Number of Participants Analyzed 401 383
Measure Type: Number
Unit of Measure: participants
Hemoglobin, Grade 3 (n=395, 383) 33 61
Platelet Count, Grade 3 (n=391, 379) 1 6
Platelet Count, Grade 4 (n=391, 379) 0 1
Leukocytes, Grade 3 (n=394, 380) 0 1
Leukocytes, Grade 4 (n=394, 380) 1 0
Lymphocytes (absolute), Grade 3 (n=391,377) 28 43
Lymphocytes (absolute), Grade 4 (n=391,377) 3 6
Absolute Neutrophil Count, Grade 3 (n=392, 378) 0 2
Absolute Neutrophil Count, Grade 4 (n=392, 378) 0 1
Alkaline Phosphatase, Grade 3 (n=400, 374) 11 3
Aspartate Aminotransferase, Grade 3 (n=400, 375) 9 6
Aspartate Aminotransferase, Grade 4 (n=400, 375) 2 0
Alanine Aminotransferase, Grade 3 (n=401, 376) 12 3
Alanine Aminotransferase, Grade 4 (n=401, 376) 1 0
Bilirubin Total, Grade 3 (n=401, 376) 3 2
Creatinine, Grade 3 (n=398, 379) 5 5
Creatinine, Grade 4 (n=398, 379) 3 1
Hypercalcemia, Grade 3 (n=339, 315) 7 1
Hypercalcemia, Grade 4 (n=339, 315) 4 1
Hypocalcemia, Grade 3 (n=339, 315) 2 4
Hypocalcemia, Grade 4 (n=339, 315) 1 0
Hyperkalemia, Grade 3 (n=352, 332) 11 7
Hyperkalemia, Grade 4 (n=352, 332) 3 0
Hypokalemia, Grade 3 (n=352, 332) 5 3
Hypermagnesmia, Grade 3 (n=196, 174) 3 0
Hypomagnesmia, Grade 3 (n=196, 174) 1 0
Hyponatremia, Grade 3 (n=353, 332) 26 22
Hyponatremia, Grade 4 (n=353, 332) 1 1
Time Frame Day of first dose to 30 days post final dose, up to May 2015 (approximately 30 months)
Adverse Event Reporting Description Study initiated: October 2012; Primary Endpoint Study Completion: May 2015; Study on-going
 
Arm/Group Title Nivolumab Everolimus
Hide Arm/Group Description Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
All-Cause Mortality
Nivolumab Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Nivolumab Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   194/406 (47.78%)   173/397 (43.58%) 
Blood and lymphatic system disorders     
Anaemia  1  7/406 (1.72%)  12/397 (3.02%) 
Cardiac disorders     
Atrial fibrillation  1  2/406 (0.49%)  2/397 (0.50%) 
Supraventricular tachycardia  1  0/406 (0.00%)  1/397 (0.25%) 
Acute coronary syndrome  1  2/406 (0.49%)  0/397 (0.00%) 
Cardiac arrest  1  0/406 (0.00%)  1/397 (0.25%) 
Cardiac failure chronic  1  0/406 (0.00%)  1/397 (0.25%) 
Angina pectoris  1  3/406 (0.74%)  0/397 (0.00%) 
Atrial flutter  1  1/406 (0.25%)  1/397 (0.25%) 
Atrioventricular block  1  1/406 (0.25%)  0/397 (0.00%) 
Cardiac failure  1  3/406 (0.74%)  1/397 (0.25%) 
Cardiac failure congestive  1  0/406 (0.00%)  2/397 (0.50%) 
Cardio-respiratory arrest  1  0/406 (0.00%)  1/397 (0.25%) 
Myocardial infarction  1  6/406 (1.48%)  1/397 (0.25%) 
Pericardial effusion  1  0/406 (0.00%)  1/397 (0.25%) 
Intracardiac thrombus  1  1/406 (0.25%)  0/397 (0.00%) 
Acute myocardial infarction  1  1/406 (0.25%)  0/397 (0.00%) 
Left ventricular dysfunction  1  1/406 (0.25%)  1/397 (0.25%) 
Ear and labyrinth disorders     
Tympanic membrane perforation  1  1/406 (0.25%)  0/397 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  3/406 (0.74%)  1/397 (0.25%) 
Eye disorders     
Vision blurred  1  1/406 (0.25%)  0/397 (0.00%) 
Corneal disorder  1  1/406 (0.25%)  0/397 (0.00%) 
Visual acuity reduced  1  1/406 (0.25%)  0/397 (0.00%) 
Gastrointestinal disorders     
Ascites  1  1/406 (0.25%)  2/397 (0.50%) 
Diabetic gastroparesis  1  1/406 (0.25%)  0/397 (0.00%) 
Enterocolitis  1  1/406 (0.25%)  0/397 (0.00%) 
Intestinal ischaemia  1  0/406 (0.00%)  1/397 (0.25%) 
Small intestinal obstruction  1  1/406 (0.25%)  5/397 (1.26%) 
Umbilical hernia  1  1/406 (0.25%)  0/397 (0.00%) 
Melaena  1  1/406 (0.25%)  0/397 (0.00%) 
Peritoneal haemorrhage  1  0/406 (0.00%)  1/397 (0.25%) 
Stomatitis  1  0/406 (0.00%)  1/397 (0.25%) 
Abdominal pain upper  1  0/406 (0.00%)  1/397 (0.25%) 
Constipation  1  5/406 (1.23%)  2/397 (0.50%) 
Ileus  1  1/406 (0.25%)  0/397 (0.00%) 
Intestinal obstruction  1  0/406 (0.00%)  2/397 (0.50%) 
Intra-abdominal haemorrhage  1  0/406 (0.00%)  1/397 (0.25%) 
Upper gastrointestinal haemorrhage  1  0/406 (0.00%)  1/397 (0.25%) 
Colitis  1  2/406 (0.49%)  0/397 (0.00%) 
Oesophageal obstruction  1  1/406 (0.25%)  0/397 (0.00%) 
Pancreatitis  1  1/406 (0.25%)  0/397 (0.00%) 
Nausea  1  2/406 (0.49%)  2/397 (0.50%) 
Rectal haemorrhage  1  0/406 (0.00%)  1/397 (0.25%) 
Vomiting  1  1/406 (0.25%)  0/397 (0.00%) 
Abdominal pain  1  4/406 (0.99%)  3/397 (0.76%) 
Diarrhoea  1  6/406 (1.48%)  2/397 (0.50%) 
Lower gastrointestinal haemorrhage  1  1/406 (0.25%)  0/397 (0.00%) 
Pneumoperitoneum  1  0/406 (0.00%)  1/397 (0.25%) 
Large intestine perforation  1  2/406 (0.49%)  0/397 (0.00%) 
General disorders     
Performance status decreased  1  0/406 (0.00%)  1/397 (0.25%) 
Influenza like illness  1  1/406 (0.25%)  0/397 (0.00%) 
Multi-organ failure  1  1/406 (0.25%)  0/397 (0.00%) 
Fatigue  1  2/406 (0.49%)  1/397 (0.25%) 
General physical health deterioration  1  2/406 (0.49%)  5/397 (1.26%) 
Impaired healing  1  0/406 (0.00%)  1/397 (0.25%) 
Pain  1  4/406 (0.99%)  2/397 (0.50%) 
Pyrexia  1  4/406 (0.99%)  5/397 (1.26%) 
Asthenia  1  1/406 (0.25%)  0/397 (0.00%) 
Hernia  1  0/406 (0.00%)  1/397 (0.25%) 
Non-cardiac chest pain  1  2/406 (0.49%)  2/397 (0.50%) 
Oedema peripheral  1  2/406 (0.49%)  1/397 (0.25%) 
Hyperpyrexia  1  1/406 (0.25%)  0/397 (0.00%) 
Hepatobiliary disorders     
Jaundice cholestatic  1  1/406 (0.25%)  0/397 (0.00%) 
Bile duct obstruction  1  0/406 (0.00%)  1/397 (0.25%) 
Autoimmune hepatitis  1  1/406 (0.25%)  0/397 (0.00%) 
Cholecystitis  1  0/406 (0.00%)  1/397 (0.25%) 
Gallbladder pain  1  0/406 (0.00%)  1/397 (0.25%) 
Hepatic pain  1  1/406 (0.25%)  0/397 (0.00%) 
Hepatocellular injury  1  1/406 (0.25%)  0/397 (0.00%) 
Immune system disorders     
Hypersensitivity  1  0/406 (0.00%)  1/397 (0.25%) 
Anaphylactic reaction  1  1/406 (0.25%)  0/397 (0.00%) 
Infections and infestations     
Bronchopneumonia  1  0/406 (0.00%)  1/397 (0.25%) 
Herpes zoster  1  0/406 (0.00%)  1/397 (0.25%) 
Periorbital cellulitis  1  1/406 (0.25%)  0/397 (0.00%) 
Staphylococcal bacteraemia  1  1/406 (0.25%)  0/397 (0.00%) 
Urinary tract infection  1  3/406 (0.74%)  3/397 (0.76%) 
Bronchitis  1  2/406 (0.49%)  0/397 (0.00%) 
Lung infection  1  1/406 (0.25%)  2/397 (0.50%) 
Pneumonia  1  11/406 (2.71%)  15/397 (3.78%) 
Sepsis  1  5/406 (1.23%)  3/397 (0.76%) 
Bronchiolitis  1  1/406 (0.25%)  0/397 (0.00%) 
Spinal cord infection  1  2/406 (0.49%)  0/397 (0.00%) 
Infective exacerbation of chronic obstructive airways disease  1  1/406 (0.25%)  0/397 (0.00%) 
Appendicitis  1  1/406 (0.25%)  0/397 (0.00%) 
Cellulitis  1  2/406 (0.49%)  0/397 (0.00%) 
Febrile infection  1  1/406 (0.25%)  0/397 (0.00%) 
Infection  1  1/406 (0.25%)  2/397 (0.50%) 
Pneumonia mycoplasmal  1  0/406 (0.00%)  1/397 (0.25%) 
Respiratory tract infection  1  1/406 (0.25%)  0/397 (0.00%) 
Splenic infection  1  0/406 (0.00%)  1/397 (0.25%) 
Upper respiratory tract infection  1  0/406 (0.00%)  1/397 (0.25%) 
Urosepsis  1  1/406 (0.25%)  0/397 (0.00%) 
Brain abscess  1  1/406 (0.25%)  0/397 (0.00%) 
Groin infection  1  0/406 (0.00%)  1/397 (0.25%) 
Lower respiratory tract infection  1  0/406 (0.00%)  1/397 (0.25%) 
Peritonitis bacterial  1  0/406 (0.00%)  1/397 (0.25%) 
Gastroenteritis  1  1/406 (0.25%)  2/397 (0.50%) 
Skin infection  1  1/406 (0.25%)  0/397 (0.00%) 
Cystitis  1  1/406 (0.25%)  0/397 (0.00%) 
Gastroenteritis viral  1  1/406 (0.25%)  0/397 (0.00%) 
Influenza  1  1/406 (0.25%)  0/397 (0.00%) 
Pneumocystis jirovecii pneumonia  1  0/406 (0.00%)  1/397 (0.25%) 
Soft tissue infection  1  1/406 (0.25%)  0/397 (0.00%) 
Injury, poisoning and procedural complications     
Clavicle fracture  1  1/406 (0.25%)  0/397 (0.00%) 
Overdose  1  0/406 (0.00%)  1/397 (0.25%) 
Spinal fracture  1  0/406 (0.00%)  1/397 (0.25%) 
Incisional hernia  1  0/406 (0.00%)  1/397 (0.25%) 
Accident  1  0/406 (0.00%)  1/397 (0.25%) 
Humerus fracture  1  1/406 (0.25%)  0/397 (0.00%) 
Spinal compression fracture  1  1/406 (0.25%)  0/397 (0.00%) 
Fall  1  1/406 (0.25%)  0/397 (0.00%) 
Post procedural complication  1  1/406 (0.25%)  0/397 (0.00%) 
Procedural pain  1  0/406 (0.00%)  1/397 (0.25%) 
Drug administration error  1  1/406 (0.25%)  0/397 (0.00%) 
Femur fracture  1  0/406 (0.00%)  2/397 (0.50%) 
Toxicity to various agents  1  1/406 (0.25%)  0/397 (0.00%) 
Cervical vertebral fracture  1  0/406 (0.00%)  1/397 (0.25%) 
Wound complication  1  1/406 (0.25%)  0/397 (0.00%) 
Investigations     
Blood glucose increased  1  1/406 (0.25%)  0/397 (0.00%) 
Blood culture positive  1  1/406 (0.25%)  0/397 (0.00%) 
Haemoglobin decreased  1  1/406 (0.25%)  0/397 (0.00%) 
Blood creatinine increased  1  2/406 (0.49%)  2/397 (0.50%) 
Alanine aminotransferase increased  1  2/406 (0.49%)  0/397 (0.00%) 
Aspartate aminotransferase increased  1  2/406 (0.49%)  0/397 (0.00%) 
Metabolism and nutrition disorders     
Cachexia  1  0/406 (0.00%)  1/397 (0.25%) 
Hypercalcaemia  1  10/406 (2.46%)  2/397 (0.50%) 
Diabetes mellitus inadequate control  1  0/406 (0.00%)  2/397 (0.50%) 
Dehydration  1  0/406 (0.00%)  3/397 (0.76%) 
Diabetic ketoacidosis  1  1/406 (0.25%)  0/397 (0.00%) 
Hyperkalaemia  1  1/406 (0.25%)  0/397 (0.00%) 
Diabetes mellitus  1  0/406 (0.00%)  1/397 (0.25%) 
Decreased appetite  1  2/406 (0.49%)  0/397 (0.00%) 
Hyperglycaemia  1  4/406 (0.99%)  5/397 (1.26%) 
Hyponatraemia  1  2/406 (0.49%)  2/397 (0.50%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  3/406 (0.74%)  1/397 (0.25%) 
Osteolysis  1  1/406 (0.25%)  1/397 (0.25%) 
Osteoporosis  1  1/406 (0.25%)  0/397 (0.00%) 
Arthralgia  1  2/406 (0.49%)  1/397 (0.25%) 
Pain in extremity  1  3/406 (0.74%)  0/397 (0.00%) 
Bone disorder  1  1/406 (0.25%)  0/397 (0.00%) 
Muscular weakness  1  1/406 (0.25%)  3/397 (0.76%) 
Pathological fracture  1  3/406 (0.74%)  1/397 (0.25%) 
Back pain  1  7/406 (1.72%)  5/397 (1.26%) 
Musculoskeletal stiffness  1  1/406 (0.25%)  0/397 (0.00%) 
Neck pain  1  1/406 (0.25%)  1/397 (0.25%) 
Osteonecrosis of jaw  1  1/406 (0.25%)  0/397 (0.00%) 
Musculoskeletal chest pain  1  0/406 (0.00%)  2/397 (0.50%) 
Musculoskeletal pain  1  1/406 (0.25%)  0/397 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant melanoma in situ  1  1/406 (0.25%)  0/397 (0.00%) 
Metastatic renal cell carcinoma  1  4/406 (0.99%)  1/397 (0.25%) 
Oesophageal adenocarcinoma  1  0/406 (0.00%)  1/397 (0.25%) 
Basal cell carcinoma  1  3/406 (0.74%)  0/397 (0.00%) 
Metastatic pain  1  1/406 (0.25%)  0/397 (0.00%) 
Lymphangiosis carcinomatosa  1  0/406 (0.00%)  1/397 (0.25%) 
Metastases to adrenals  1  1/406 (0.25%)  0/397 (0.00%) 
Metastases to central nervous system  1  6/406 (1.48%)  0/397 (0.00%) 
Metastases to pancreas  1  2/406 (0.49%)  0/397 (0.00%) 
Metastases to bone  1  1/406 (0.25%)  1/397 (0.25%) 
Neoplasm malignant  1  1/406 (0.25%)  0/397 (0.00%) 
Lung adenocarcinoma  1  1/406 (0.25%)  0/397 (0.00%) 
Cancer pain  1  4/406 (0.99%)  0/397 (0.00%) 
Intracranial tumour haemorrhage  1  1/406 (0.25%)  0/397 (0.00%) 
Duodenal neoplasm  1  0/406 (0.00%)  1/397 (0.25%) 
Malignant neoplasm progression  1  22/406 (5.42%)  24/397 (6.05%) 
Metastatic neoplasm  1  0/406 (0.00%)  2/397 (0.50%) 
Tumour pain  1  2/406 (0.49%)  2/397 (0.50%) 
Malignant melanoma  1  1/406 (0.25%)  0/397 (0.00%) 
Metastases to lung  1  1/406 (0.25%)  1/397 (0.25%) 
Metastases to spine  1  0/406 (0.00%)  1/397 (0.25%) 
Squamous cell carcinoma  1  1/406 (0.25%)  0/397 (0.00%) 
Nervous system disorders     
Nerve compression  1  0/406 (0.00%)  1/397 (0.25%) 
Cerebral haemorrhage  1  2/406 (0.49%)  0/397 (0.00%) 
Spinal cord compression  1  8/406 (1.97%)  2/397 (0.50%) 
Thalamus haemorrhage  1  0/406 (0.00%)  1/397 (0.25%) 
Intraventricular haemorrhage  1  1/406 (0.25%)  0/397 (0.00%) 
Somnolence  1  1/406 (0.25%)  0/397 (0.00%) 
Haemorrhage intracranial  1  2/406 (0.49%)  0/397 (0.00%) 
Seizure  1  0/406 (0.00%)  1/397 (0.25%) 
Vasogenic cerebral oedema  1  1/406 (0.25%)  0/397 (0.00%) 
Central nervous system haemorrhage  1  1/406 (0.25%)  0/397 (0.00%) 
Cerebral ischaemia  1  2/406 (0.49%)  0/397 (0.00%) 
Cerebrovascular accident  1  1/406 (0.25%)  3/397 (0.76%) 
Dural arteriovenous fistula  1  1/406 (0.25%)  0/397 (0.00%) 
Syncope  1  1/406 (0.25%)  0/397 (0.00%) 
Psychiatric disorders     
Completed suicide  1  1/406 (0.25%)  1/397 (0.25%) 
Confusional state  1  0/406 (0.00%)  1/397 (0.25%) 
Mental status changes  1  1/406 (0.25%)  0/397 (0.00%) 
Renal and urinary disorders     
Renal tubular necrosis  1  0/406 (0.00%)  1/397 (0.25%) 
Renal impairment  1  2/406 (0.49%)  1/397 (0.25%) 
Acute kidney injury  1  8/406 (1.97%)  5/397 (1.26%) 
Renal colic  1  0/406 (0.00%)  1/397 (0.25%) 
Renal mass  1  1/406 (0.25%)  0/397 (0.00%) 
Haematuria  1  0/406 (0.00%)  1/397 (0.25%) 
Renal failure  1  5/406 (1.23%)  0/397 (0.00%) 
Nephrolithiasis  1  1/406 (0.25%)  2/397 (0.50%) 
Tubulointerstitial nephritis  1  1/406 (0.25%)  0/397 (0.00%) 
Dysuria  1  0/406 (0.00%)  1/397 (0.25%) 
Urinary tract obstruction  1  1/406 (0.25%)  0/397 (0.00%) 
Urinary incontinence  1  0/406 (0.00%)  1/397 (0.25%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  6/406 (1.48%)  4/397 (1.01%) 
Respiratory distress  1  0/406 (0.00%)  1/397 (0.25%) 
Haemoptysis  1  4/406 (0.99%)  1/397 (0.25%) 
Hypoxia  1  2/406 (0.49%)  2/397 (0.50%) 
Interstitial lung disease  1  0/406 (0.00%)  3/397 (0.76%) 
Organising pneumonia  1  1/406 (0.25%)  0/397 (0.00%) 
Pleurisy  1  1/406 (0.25%)  0/397 (0.00%) 
Pulmonary embolism  1  4/406 (0.99%)  7/397 (1.76%) 
Pneumothorax spontaneous  1  0/406 (0.00%)  1/397 (0.25%) 
Acute respiratory failure  1  0/406 (0.00%)  1/397 (0.25%) 
Lung disorder  1  0/406 (0.00%)  1/397 (0.25%) 
Pneumonitis  1  8/406 (1.97%)  12/397 (3.02%) 
Bronchial obstruction  1  1/406 (0.25%)  1/397 (0.25%) 
Cough  1  1/406 (0.25%)  1/397 (0.25%) 
Pneumothorax  1  1/406 (0.25%)  0/397 (0.00%) 
Pleural effusion  1  14/406 (3.45%)  13/397 (3.27%) 
Pulmonary haemorrhage  1  1/406 (0.25%)  0/397 (0.00%) 
Acute pulmonary oedema  1  0/406 (0.00%)  1/397 (0.25%) 
Chronic obstructive pulmonary disease  1  0/406 (0.00%)  1/397 (0.25%) 
Pulmonary infarction  1  0/406 (0.00%)  1/397 (0.25%) 
Respiratory failure  1  0/406 (0.00%)  2/397 (0.50%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme  1  1/406 (0.25%)  1/397 (0.25%) 
Rash maculo-papular  1  1/406 (0.25%)  0/397 (0.00%) 
Angioedema  1  0/406 (0.00%)  2/397 (0.50%) 
Skin lesion  1  1/406 (0.25%)  0/397 (0.00%) 
Vascular disorders     
Venous thrombosis  1  1/406 (0.25%)  0/397 (0.00%) 
Hypotension  1  2/406 (0.49%)  1/397 (0.25%) 
Lymphoedema  1  0/406 (0.00%)  1/397 (0.25%) 
Hypertensive crisis  1  1/406 (0.25%)  0/397 (0.00%) 
Circulatory collapse  1  0/406 (0.00%)  1/397 (0.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nivolumab Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   388/406 (95.57%)   375/397 (94.46%) 
Blood and lymphatic system disorders     
Anaemia  1  75/406 (18.47%)  136/397 (34.26%) 
Endocrine disorders     
Hypothyroidism  1  28/406 (6.90%)  6/397 (1.51%) 
Gastrointestinal disorders     
Dry mouth  1  26/406 (6.40%)  18/397 (4.53%) 
Stomatitis  1  20/406 (4.93%)  125/397 (31.49%) 
Abdominal pain upper  1  25/406 (6.16%)  14/397 (3.53%) 
Constipation  1  90/406 (22.17%)  73/397 (18.39%) 
Nausea  1  115/406 (28.33%)  112/397 (28.21%) 
Vomiting  1  66/406 (16.26%)  63/397 (15.87%) 
Abdominal pain  1  34/406 (8.37%)  29/397 (7.30%) 
Diarrhoea  1  95/406 (23.40%)  123/397 (30.98%) 
General disorders     
Fatigue  1  194/406 (47.78%)  177/397 (44.58%) 
Pyrexia  1  64/406 (15.76%)  78/397 (19.65%) 
Asthenia  1  36/406 (8.87%)  65/397 (16.37%) 
Mucosal inflammation  1  15/406 (3.69%)  82/397 (20.65%) 
Oedema peripheral  1  58/406 (14.29%)  101/397 (25.44%) 
Chills  1  29/406 (7.14%)  23/397 (5.79%) 
Infections and infestations     
Urinary tract infection  1  21/406 (5.17%)  19/397 (4.79%) 
Nasopharyngitis  1  37/406 (9.11%)  18/397 (4.53%) 
Upper respiratory tract infection  1  30/406 (7.39%)  21/397 (5.29%) 
Investigations     
Blood alkaline phosphatase increased  1  27/406 (6.65%)  14/397 (3.53%) 
Blood cholesterol increased  1  7/406 (1.72%)  31/397 (7.81%) 
Weight decreased  1  45/406 (11.08%)  58/397 (14.61%) 
Blood creatinine increased  1  55/406 (13.55%)  49/397 (12.34%) 
Alanine aminotransferase increased  1  26/406 (6.40%)  23/397 (5.79%) 
Aspartate aminotransferase increased  1  31/406 (7.64%)  25/397 (6.30%) 
Metabolism and nutrition disorders     
Hypercalcaemia  1  21/406 (5.17%)  11/397 (2.77%) 
Hypercholesterolaemia  1  2/406 (0.49%)  37/397 (9.32%) 
Hypertriglyceridaemia  1  21/406 (5.17%)  75/397 (18.89%) 
Hyperkalaemia  1  23/406 (5.67%)  15/397 (3.78%) 
Decreased appetite  1  92/406 (22.66%)  121/397 (30.48%) 
Hyperglycaemia  1  32/406 (7.88%)  60/397 (15.11%) 
Hyponatraemia  1  22/406 (5.42%)  17/397 (4.28%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  80/406 (19.70%)  57/397 (14.36%) 
Pain in extremity  1  48/406 (11.82%)  35/397 (8.82%) 
Back pain  1  83/406 (20.44%)  59/397 (14.86%) 
Flank pain  1  21/406 (5.17%)  15/397 (3.78%) 
Musculoskeletal chest pain  1  25/406 (6.16%)  16/397 (4.03%) 
Musculoskeletal pain  1  40/406 (9.85%)  21/397 (5.29%) 
Myalgia  1  39/406 (9.61%)  14/397 (3.53%) 
Nervous system disorders     
Dizziness  1  35/406 (8.62%)  31/397 (7.81%) 
Headache  1  57/406 (14.04%)  55/397 (13.85%) 
Dysgeusia  1  14/406 (3.45%)  53/397 (13.35%) 
Psychiatric disorders     
Anxiety  1  27/406 (6.65%)  20/397 (5.04%) 
Insomnia  1  28/406 (6.90%)  26/397 (6.55%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  91/406 (22.41%)  105/397 (26.45%) 
Epistaxis  1  10/406 (2.46%)  56/397 (14.11%) 
Nasal congestion  1  23/406 (5.67%)  12/397 (3.02%) 
Haemoptysis  1  22/406 (5.42%)  12/397 (3.02%) 
Oropharyngeal pain  1  12/406 (2.96%)  24/397 (6.05%) 
Dyspnoea exertional  1  19/406 (4.68%)  22/397 (5.54%) 
Pneumonitis  1  17/406 (4.19%)  55/397 (13.85%) 
Cough  1  129/406 (31.77%)  140/397 (35.26%) 
Dysphonia  1  25/406 (6.16%)  18/397 (4.53%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  75/406 (18.47%)  50/397 (12.59%) 
Rash  1  64/406 (15.76%)  92/397 (23.17%) 
Rash maculo-papular  1  18/406 (4.43%)  20/397 (5.04%) 
Palmar-plantar erythrodysaesthesia syndrome  1  10/406 (2.46%)  25/397 (6.30%) 
Dry skin  1  41/406 (10.10%)  44/397 (11.08%) 
Dermatitis acneiform  1  12/406 (2.96%)  21/397 (5.29%) 
Vascular disorders     
Hypertension  1  35/406 (8.62%)  28/397 (7.05%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01668784     History of Changes
Other Study ID Numbers: CA209-025
2011‐005132‐26 ( EudraCT Number )
First Submitted: August 16, 2012
First Posted: August 20, 2012
Results First Submitted: March 28, 2016
Results First Posted: April 29, 2016
Last Update Posted: August 9, 2019