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An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) (CheckMate 498)

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ClinicalTrials.gov Identifier: NCT02617589
Recruitment Status : Active, not recruiting
First Posted : December 1, 2015
Results First Posted : February 3, 2021
Last Update Posted : February 3, 2021
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 Brain Cancer
Interventions Drug: Nivolumab
Drug: Temozolomide
Radiation: Radiotherapy
Enrollment 560
Recruitment Details  
Pre-assignment Details 560 Randomized and treated.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description nivolumab + radiation therapy(RT) temozolomide (TMZ) + radiation therapy
Period Title: All Randomized
Started [1] 280 280
Completed [2] 278 275
Not Completed 2 5
Reason Not Completed
Request to discontinue study treatment             1             3
Participant Withdrew Consent             1             2
[1]
Started = Number Randomized
[2]
Completed = Participants continuing to Treatment
Period Title: Treatment Period
Started [1] 278 275
Completed [2] 4 1
Not Completed 274 274
Reason Not Completed
Other Reasons             2             2
Not reported             1             0
Poor/Non compliance             1             1
Maximum Clinical Benefit             0             2
Participant Withdrew Consent             2             6
Participant Request to discontinue             12             20
Adverse event unrelated to study drug             15             9
Death             1             1
Study Drug Toxicity             26             20
Disease Progression             214             137
Completed Treatment             0             76
[1]
= Entering Treatment Period
[2]
= not continuing in Treatment Period
Arm/Group Title Treatment A Treatment B Total
Hide Arm/Group Description nivolumab + radiation therapy(RT) temozolomide (TMZ) + radiation therapy Total of all reporting groups
Overall Number of Baseline Participants 280 280 560
Hide Baseline Analysis Population Description
Baseline characteristics were summarized using all randomized subjects (all enrolled subjects who were randomized to any treatment arm)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 280 participants 280 participants 560 participants
58.8  (10.8) 56.5  (11.3) 57.6  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 280 participants 280 participants 560 participants
Female
90
  32.1%
105
  37.5%
195
  34.8%
Male
190
  67.9%
175
  62.5%
365
  65.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 280 participants 280 participants 560 participants
Hispanic or Latino
3
   1.1%
2
   0.7%
5
   0.9%
Not Hispanic or Latino
113
  40.4%
95
  33.9%
208
  37.1%
Unknown or Not Reported
164
  58.6%
183
  65.4%
347
  62.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 280 participants 280 participants 560 participants
White 231 240 471
Black or African American 4 3 7
Asian 33 28 61
Other 12 9 21
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died will be censored at the last known alive date.
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants: All enrolled Participants who were randomized to any treatment arm.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:
nivolumab + radiation Therapy
temozolomide (TMZ) + radiation therapy
Overall Number of Participants Analyzed 280 280
Median (95% Confidence Interval)
Unit of Measure: Months
13.40
(12.62 to 14.29)
14.88
(13.27 to 16.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Hazard Ratio is Nivolumab over Temozolomide
Statistical Test of Hypothesis P-Value 0.0037
Comments [Not Specified]
Method Log-rank test stratified
Comments Log-rank test stratified by complete or partial resection at baseline as entered into the IVRS.
Method of Estimation Estimation Parameter Stratified Cox proportional hazard model
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
1.09 to 1.58
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Participants who did not have disease progression or who did not die will be censored at the date of last tumor assessment. Participants who did not have any on study tumor assessment and did not have tumor progression or die will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. Participants who had surgical resection post start of study treatment will be censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on RANO criteria
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:
nivolumab + radiation Therapy
temozolomide (TMZ) + radiation therapy
Overall Number of Participants Analyzed 280 280
Median (95% Confidence Interval)
Unit of Measure: Months
6.01
(5.65 to 6.21)
6.21
(5.91 to 6.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Hazard Ratio is Nivolumab over Temozolomide
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Log-rank test stratified
Comments Log-rank test stratified by complete or partial resection at baseline as entered into the IVRS.
Method of Estimation Estimation Parameter Stratified Cox proportional hazard model
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
1.15 to 1.65
Estimation Comments [Not Specified]
3.Secondary Outcome
Title OS at 24 Months
Hide Description The OS rate at 24 months of nivolumab + RT and RT + TMZ was estimated as Kaplan-Meier probability of survival at 24 months.
Time Frame at 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Participants
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:
nivolumab + radiation Therapy
temozolomide (TMZ) + radiation therapy
Overall Number of Participants Analyzed 280 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Survival
10.3
(6.8 to 14.6)
21.2
(16.4 to 26.5)
4.Secondary Outcome
Title OS in Tumor Mutational Burden (TMB) High Population
Hide Description OS is defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died will be censored at the last known alive date.
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
TMB-High Population
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:
nivolumab + radiation Therapy
temozolomide (TMZ) + radiation therapy
Overall Number of Participants Analyzed 280 280
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The analysis of OS in the TMB-high population was not performed due to TMB status not being assessed because of limited tissue availability
5.Secondary Outcome
Title PFS in Tumor Mutational Burden (TMB) High Population
Hide Description PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Participants who did not have disease progression or who did not die will be censored at the date of last tumor assessment. Participants who did not have any on study tumor assessment and did not have tumor progression or die will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. Participants who had surgical resection post start of study treatment will be censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on RANO criteria
Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
TMB-High Population
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:
nivolumab + radiation Therapy
temozolomide (TMZ) + radiation therapy
Overall Number of Participants Analyzed 280 280
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The analysis of PFS in the TMB-high population was not performed due to TMB status not being assessed because of limited tissue availability
Time Frame 3 years, SAE and AE summaries includes adverse events from first dose date and 100 days after last dose of study therapy
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description nivolumab + radiation Therapy temozolomide (TMZ) + radiation therapy
All-Cause Mortality
Treatment A Treatment B
Affected / at Risk (%) Affected / at Risk (%)
Total   242/278 (87.05%)   216/275 (78.55%) 
Hide Serious Adverse Events
Treatment A Treatment B
Affected / at Risk (%) Affected / at Risk (%)
Total   205/278 (73.74%)   140/275 (50.91%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  2/278 (0.72%)  0/275 (0.00%) 
Febrile neutropenia  1  0/278 (0.00%)  1/275 (0.36%) 
Leukopenia  1  0/278 (0.00%)  1/275 (0.36%) 
Lymphopenia  1  0/278 (0.00%)  1/275 (0.36%) 
Neutropenia  1  1/278 (0.36%)  2/275 (0.73%) 
Thrombocytopenia  1  1/278 (0.36%)  8/275 (2.91%) 
Cardiac disorders     
Arrhythmia  1  0/278 (0.00%)  1/275 (0.36%) 
Atrial fibrillation  1  0/278 (0.00%)  2/275 (0.73%) 
Cardiac arrest  1  1/278 (0.36%)  0/275 (0.00%) 
Stress cardiomyopathy  1  0/278 (0.00%)  1/275 (0.36%) 
Endocrine disorders     
Hypophysitis  1  1/278 (0.36%)  0/275 (0.00%) 
Hypothyroidism  1  1/278 (0.36%)  0/275 (0.00%) 
Eye disorders     
Retinal detachment  1  1/278 (0.36%)  0/275 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/278 (0.36%)  0/275 (0.00%) 
Constipation  1  0/278 (0.00%)  2/275 (0.73%) 
Diarrhoea  1  5/278 (1.80%)  1/275 (0.36%) 
Gastrointestinal inflammation  1  0/278 (0.00%)  1/275 (0.36%) 
Gastrointestinal perforation  1  1/278 (0.36%)  0/275 (0.00%) 
Ileus  1  1/278 (0.36%)  0/275 (0.00%) 
Inguinal hernia  1  1/278 (0.36%)  0/275 (0.00%) 
Intestinal obstruction  1  0/278 (0.00%)  1/275 (0.36%) 
Nausea  1  1/278 (0.36%)  4/275 (1.45%) 
Oesophagitis  1  1/278 (0.36%)  0/275 (0.00%) 
Pancreatitis  1  1/278 (0.36%)  0/275 (0.00%) 
Pancreatitis acute  1  0/278 (0.00%)  1/275 (0.36%) 
Vomiting  1  5/278 (1.80%)  2/275 (0.73%) 
General disorders     
Adverse event  1  1/278 (0.36%)  1/275 (0.36%) 
Asthenia  1  1/278 (0.36%)  1/275 (0.36%) 
Condition aggravated  1  0/278 (0.00%)  2/275 (0.73%) 
Disease progression  1  3/278 (1.08%)  0/275 (0.00%) 
Euthanasia  1  0/278 (0.00%)  1/275 (0.36%) 
Fatigue  1  2/278 (0.72%)  1/275 (0.36%) 
Gait disturbance  1  2/278 (0.72%)  0/275 (0.00%) 
General physical health deterioration  1  7/278 (2.52%)  3/275 (1.09%) 
Impaired healing  1  1/278 (0.36%)  0/275 (0.00%) 
Malaise  1  3/278 (1.08%)  0/275 (0.00%) 
Multiple organ dysfunction syndrome  1  2/278 (0.72%)  0/275 (0.00%) 
Polyserositis  1  1/278 (0.36%)  0/275 (0.00%) 
Pyrexia  1  7/278 (2.52%)  2/275 (0.73%) 
Sudden death  1  2/278 (0.72%)  1/275 (0.36%) 
Hepatobiliary disorders     
Autoimmune hepatitis  1  1/278 (0.36%)  0/275 (0.00%) 
Cholecystitis acute  1  0/278 (0.00%)  1/275 (0.36%) 
Drug-induced liver injury  1  3/278 (1.08%)  0/275 (0.00%) 
Hepatic function abnormal  1  2/278 (0.72%)  0/275 (0.00%) 
Hepatitis  1  1/278 (0.36%)  0/275 (0.00%) 
Hepatotoxicity  1  1/278 (0.36%)  0/275 (0.00%) 
Immune system disorders     
Autoimmune disorder  1  1/278 (0.36%)  0/275 (0.00%) 
Infections and infestations     
Anal abscess  1  0/278 (0.00%)  1/275 (0.36%) 
Appendicitis  1  0/278 (0.00%)  1/275 (0.36%) 
Brain abscess  1  1/278 (0.36%)  0/275 (0.00%) 
Bronchitis  1  1/278 (0.36%)  1/275 (0.36%) 
Encephalitis  1  0/278 (0.00%)  1/275 (0.36%) 
Gastroenteritis viral  1  0/278 (0.00%)  1/275 (0.36%) 
Hepatitis viral  1  1/278 (0.36%)  0/275 (0.00%) 
Herpes zoster  1  0/278 (0.00%)  1/275 (0.36%) 
Lung infection  1  1/278 (0.36%)  0/275 (0.00%) 
Meningitis  1  1/278 (0.36%)  1/275 (0.36%) 
Meningitis aseptic  1  2/278 (0.72%)  0/275 (0.00%) 
Pneumonia  1  6/278 (2.16%)  2/275 (0.73%) 
Postoperative wound infection  1  0/278 (0.00%)  1/275 (0.36%) 
Respiratory tract infection  1  1/278 (0.36%)  0/275 (0.00%) 
Sepsis  1  1/278 (0.36%)  0/275 (0.00%) 
Skin infection  1  2/278 (0.72%)  0/275 (0.00%) 
Staphylococcal infection  1  0/278 (0.00%)  1/275 (0.36%) 
Upper respiratory tract infection  1  0/278 (0.00%)  1/275 (0.36%) 
Urinary tract infection  1  1/278 (0.36%)  2/275 (0.73%) 
Urosepsis  1  0/278 (0.00%)  1/275 (0.36%) 
Wound infection  1  2/278 (0.72%)  1/275 (0.36%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/278 (0.00%)  1/275 (0.36%) 
Compression fracture  1  0/278 (0.00%)  1/275 (0.36%) 
Fall  1  3/278 (1.08%)  1/275 (0.36%) 
Femur fracture  1  0/278 (0.00%)  1/275 (0.36%) 
Head injury  1  1/278 (0.36%)  0/275 (0.00%) 
Humerus fracture  1  1/278 (0.36%)  0/275 (0.00%) 
Infusion related reaction  1  1/278 (0.36%)  0/275 (0.00%) 
Pseudomeningocele  1  1/278 (0.36%)  0/275 (0.00%) 
Pubis fracture  1  0/278 (0.00%)  1/275 (0.36%) 
Spinal compression fracture  1  1/278 (0.36%)  1/275 (0.36%) 
Spinal fracture  1  0/278 (0.00%)  1/275 (0.36%) 
Subdural haematoma  1  2/278 (0.72%)  1/275 (0.36%) 
Wound  1  0/278 (0.00%)  1/275 (0.36%) 
Wound dehiscence  1  1/278 (0.36%)  0/275 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  0/278 (0.00%)  1/275 (0.36%) 
Aspartate aminotransferase increased  1  0/278 (0.00%)  1/275 (0.36%) 
Blood creatinine increased  1  1/278 (0.36%)  0/275 (0.00%) 
Blood glucose increased  1  0/278 (0.00%)  1/275 (0.36%) 
Fibrin D dimer increased  1  0/278 (0.00%)  1/275 (0.36%) 
Hepatic enzyme increased  1  1/278 (0.36%)  0/275 (0.00%) 
Platelet count decreased  1  0/278 (0.00%)  4/275 (1.45%) 
Transaminases increased  1  0/278 (0.00%)  1/275 (0.36%) 
Troponin increased  1  1/278 (0.36%)  0/275 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/278 (1.08%)  0/275 (0.00%) 
Hyperglycaemia  1  5/278 (1.80%)  2/275 (0.73%) 
Hypernatraemia  1  0/278 (0.00%)  1/275 (0.36%) 
Hyponatraemia  1  4/278 (1.44%)  1/275 (0.36%) 
Metabolic acidosis  1  1/278 (0.36%)  0/275 (0.00%) 
Steroid diabetes  1  0/278 (0.00%)  1/275 (0.36%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/278 (0.36%)  1/275 (0.36%) 
Fistula  1  1/278 (0.36%)  0/275 (0.00%) 
Muscular weakness  1  1/278 (0.36%)  4/275 (1.45%) 
Myopathy  1  1/278 (0.36%)  0/275 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Glioblastoma  1  6/278 (2.16%)  0/275 (0.00%) 
Glioblastoma multiforme  1  1/278 (0.36%)  0/275 (0.00%) 
Malignant neoplasm progression  1  86/278 (30.94%)  54/275 (19.64%) 
Metastases to meninges  1  1/278 (0.36%)  0/275 (0.00%) 
Neoplasm  1  2/278 (0.72%)  0/275 (0.00%) 
Neoplasm malignant  1  1/278 (0.36%)  0/275 (0.00%) 
Neoplasm progression  1  4/278 (1.44%)  3/275 (1.09%) 
Recurrent cancer  1  0/278 (0.00%)  1/275 (0.36%) 
Tumour flare  1  14/278 (5.04%)  0/275 (0.00%) 
Tumour pseudoprogression  1  2/278 (0.72%)  1/275 (0.36%) 
Nervous system disorders     
Aphasia  1  4/278 (1.44%)  3/275 (1.09%) 
Ataxia  1  2/278 (0.72%)  0/275 (0.00%) 
Brain oedema  1  6/278 (2.16%)  8/275 (2.91%) 
Cerebellar stroke  1  1/278 (0.36%)  0/275 (0.00%) 
Cerebral haemorrhage  1  1/278 (0.36%)  1/275 (0.36%) 
Cerebral ischaemia  1  1/278 (0.36%)  1/275 (0.36%) 
Cerebrospinal fluid leakage  1  0/278 (0.00%)  1/275 (0.36%) 
Depressed level of consciousness  1  1/278 (0.36%)  1/275 (0.36%) 
Dizziness  1  2/278 (0.72%)  0/275 (0.00%) 
Encephalopathy  1  4/278 (1.44%)  1/275 (0.36%) 
Epilepsy  1  9/278 (3.24%)  11/275 (4.00%) 
Generalised tonic-clonic seizure  1  0/278 (0.00%)  2/275 (0.73%) 
Haemorrhage intracranial  1  2/278 (0.72%)  1/275 (0.36%) 
Headache  1  12/278 (4.32%)  5/275 (1.82%) 
Hemianopia  1  0/278 (0.00%)  1/275 (0.36%) 
Hemiparesis  1  9/278 (3.24%)  6/275 (2.18%) 
Hydrocephalus  1  2/278 (0.72%)  1/275 (0.36%) 
IIIrd nerve disorder  1  0/278 (0.00%)  1/275 (0.36%) 
Intracranial pressure increased  1  2/278 (0.72%)  3/275 (1.09%) 
Ischaemic stroke  1  1/278 (0.36%)  0/275 (0.00%) 
Lethargy  1  1/278 (0.36%)  1/275 (0.36%) 
Loss of consciousness  1  0/278 (0.00%)  1/275 (0.36%) 
Migraine  1  1/278 (0.36%)  0/275 (0.00%) 
Nervous system disorder  1  1/278 (0.36%)  2/275 (0.73%) 
Neurological decompensation  1  1/278 (0.36%)  1/275 (0.36%) 
Neurological symptom  1  1/278 (0.36%)  0/275 (0.00%) 
Paraesthesia  1  1/278 (0.36%)  0/275 (0.00%) 
Partial seizures  1  4/278 (1.44%)  1/275 (0.36%) 
Seizure  1  37/278 (13.31%)  30/275 (10.91%) 
Subdural hygroma  1  0/278 (0.00%)  1/275 (0.36%) 
Syncope  1  1/278 (0.36%)  0/275 (0.00%) 
Transient ischaemic attack  1  1/278 (0.36%)  0/275 (0.00%) 
Vasogenic cerebral oedema  1  2/278 (0.72%)  0/275 (0.00%) 
Visual field defect  1  1/278 (0.36%)  0/275 (0.00%) 
Psychiatric disorders     
Agitation  1  2/278 (0.72%)  0/275 (0.00%) 
Anxiety  1  0/278 (0.00%)  1/275 (0.36%) 
Apathy  1  1/278 (0.36%)  0/275 (0.00%) 
Confusional state  1  3/278 (1.08%)  4/275 (1.45%) 
Drug dependence  1  0/278 (0.00%)  1/275 (0.36%) 
Major depression  1  1/278 (0.36%)  0/275 (0.00%) 
Mental status changes  1  3/278 (1.08%)  0/275 (0.00%) 
Mood altered  1  1/278 (0.36%)  0/275 (0.00%) 
Personality change  1  1/278 (0.36%)  0/275 (0.00%) 
Suicidal ideation  1  0/278 (0.00%)  1/275 (0.36%) 
Renal and urinary disorders     
Acute kidney injury  1  2/278 (0.72%)  0/275 (0.00%) 
Haematuria  1  1/278 (0.36%)  0/275 (0.00%) 
Nephrolithiasis  1  0/278 (0.00%)  1/275 (0.36%) 
Urinary incontinence  1  1/278 (0.36%)  0/275 (0.00%) 
Urinary retention  1  1/278 (0.36%)  0/275 (0.00%) 
Reproductive system and breast disorders     
Testicular disorder  1  1/278 (0.36%)  0/275 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/278 (0.36%)  0/275 (0.00%) 
Chronic obstructive pulmonary disease  1  1/278 (0.36%)  0/275 (0.00%) 
Dyspnoea  1  0/278 (0.00%)  1/275 (0.36%) 
Hiccups  1  0/278 (0.00%)  1/275 (0.36%) 
Interstitial lung disease  1  1/278 (0.36%)  0/275 (0.00%) 
Lung consolidation  1  0/278 (0.00%)  1/275 (0.36%) 
Pneumonia aspiration  1  2/278 (0.72%)  0/275 (0.00%) 
Pneumonitis  1  1/278 (0.36%)  0/275 (0.00%) 
Pulmonary embolism  1  7/278 (2.52%)  9/275 (3.27%) 
Respiratory failure  1  2/278 (0.72%)  1/275 (0.36%) 
Skin and subcutaneous tissue disorders     
Dermatitis exfoliative generalised  1  1/278 (0.36%)  0/275 (0.00%) 
Rash  1  3/278 (1.08%)  1/275 (0.36%) 
Rash macular  1  1/278 (0.36%)  0/275 (0.00%) 
Rash maculo-papular  1  2/278 (0.72%)  2/275 (0.73%) 
Skin toxicity  1  1/278 (0.36%)  0/275 (0.00%) 
Surgical and medical procedures     
Cranioplasty  1  0/278 (0.00%)  1/275 (0.36%) 
Surgery  1  1/278 (0.36%)  0/275 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/278 (0.36%)  5/275 (1.82%) 
Embolism  1  6/278 (2.16%)  2/275 (0.73%) 
Haematoma  1  1/278 (0.36%)  2/275 (0.73%) 
Venous thrombosis  1  0/278 (0.00%)  1/275 (0.36%) 
1
Term from vocabulary, 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment A Treatment B
Affected / at Risk (%) Affected / at Risk (%)
Total   261/278 (93.88%)   258/275 (93.82%) 
Blood and lymphatic system disorders     
Anaemia  1  16/278 (5.76%)  11/275 (4.00%) 
Lymphopenia  1  7/278 (2.52%)  24/275 (8.73%) 
Neutropenia  1  1/278 (0.36%)  16/275 (5.82%) 
Thrombocytopenia  1  4/278 (1.44%)  26/275 (9.45%) 
Endocrine disorders     
Hypothyroidism  1  18/278 (6.47%)  2/275 (0.73%) 
Eye disorders     
Vision blurred  1  16/278 (5.76%)  4/275 (1.45%) 
Gastrointestinal disorders     
Abdominal pain  1  16/278 (5.76%)  7/275 (2.55%) 
Constipation  1  53/278 (19.06%)  79/275 (28.73%) 
Diarrhoea  1  45/278 (16.19%)  23/275 (8.36%) 
Nausea  1  66/278 (23.74%)  105/275 (38.18%) 
Vomiting  1  35/278 (12.59%)  62/275 (22.55%) 
General disorders     
Asthenia  1  24/278 (8.63%)  25/275 (9.09%) 
Fatigue  1  121/278 (43.53%)  126/275 (45.82%) 
Gait disturbance  1  23/278 (8.27%)  6/275 (2.18%) 
Malaise  1  14/278 (5.04%)  13/275 (4.73%) 
Oedema peripheral  1  16/278 (5.76%)  15/275 (5.45%) 
Pyrexia  1  30/278 (10.79%)  16/275 (5.82%) 
Infections and infestations     
Nasopharyngitis  1  20/278 (7.19%)  13/275 (4.73%) 
Urinary tract infection  1  24/278 (8.63%)  14/275 (5.09%) 
Injury, poisoning and procedural complications     
Fall  1  14/278 (5.04%)  13/275 (4.73%) 
Radiation skin injury  1  30/278 (10.79%)  23/275 (8.36%) 
Investigations     
Alanine aminotransferase increased  1  23/278 (8.27%)  20/275 (7.27%) 
Lymphocyte count decreased  1  15/278 (5.40%)  32/275 (11.64%) 
Neutrophil count decreased  1  3/278 (1.08%)  18/275 (6.55%) 
Platelet count decreased  1  8/278 (2.88%)  41/275 (14.91%) 
Weight decreased  1  19/278 (6.83%)  20/275 (7.27%) 
White blood cell count decreased  1  6/278 (2.16%)  15/275 (5.45%) 
Metabolism and nutrition disorders     
Decreased appetite  1  33/278 (11.87%)  49/275 (17.82%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  20/278 (7.19%)  11/275 (4.00%) 
Back pain  1  18/278 (6.47%)  17/275 (6.18%) 
Nervous system disorders     
Aphasia  1  29/278 (10.43%)  18/275 (6.55%) 
Cognitive disorder  1  14/278 (5.04%)  11/275 (4.00%) 
Dizziness  1  40/278 (14.39%)  19/275 (6.91%) 
Dysgeusia  1  18/278 (6.47%)  17/275 (6.18%) 
Headache  1  113/278 (40.65%)  95/275 (34.55%) 
Hemiparesis  1  24/278 (8.63%)  11/275 (4.00%) 
Memory impairment  1  19/278 (6.83%)  13/275 (4.73%) 
Seizure  1  35/278 (12.59%)  34/275 (12.36%) 
Somnolence  1  19/278 (6.83%)  8/275 (2.91%) 
Psychiatric disorders     
Anxiety  1  18/278 (6.47%)  9/275 (3.27%) 
Confusional state  1  23/278 (8.27%)  13/275 (4.73%) 
Depression  1  23/278 (8.27%)  12/275 (4.36%) 
Insomnia  1  29/278 (10.43%)  18/275 (6.55%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  20/278 (7.19%)  11/275 (4.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  73/278 (26.26%)  88/275 (32.00%) 
Pruritus  1  30/278 (10.79%)  22/275 (8.00%) 
Rash  1  40/278 (14.39%)  17/275 (6.18%) 
Vascular disorders     
Hypertension  1  17/278 (6.12%)  12/275 (4.36%) 
1
Term from vocabulary, 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please Email
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02617589    
Other Study ID Numbers: CA209-498
2015-003739-37 ( EudraCT Number )
First Submitted: November 26, 2015
First Posted: December 1, 2015
Results First Submitted: November 30, 2020
Results First Posted: February 3, 2021
Last Update Posted: February 3, 2021