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)

• ClinicalTrials.gov Identifier: NCT02617589
• Recruitment Status: Completed
• First Posted: December 1, 2015
• Results First Posted: February 3, 2021
• Last Update Posted: March 28, 2023
• Sponsor: Bristol-Myers Squibb
• 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

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
Period Title: Randomization
Started	280	280
Completed	278	275
Not Completed	2	5
Reason Not Completed
Request to Discontinue Study Treatment	1	3
Participant Withdrew Consent	1	2
Period Title: Treatment
Started	278	275
Completed	0	76
Not Completed	278	199
Reason Not Completed
Other Reasons	3	3
Poor/Non Compliance	1	1
Maximum Clinical Benefit	0	2
Participant Withdrew Consent	2	6
Participant Request to Discontinue	12	21
Adverse Event Unrelated to Study Drug	16	9
Death	1	1
Study Drug Toxicity	27	20
Disease Progression	216	136

Baseline Characteristics

Arm/Group Title		Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy	Total
Arm/Group Description		Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally	Total of all reporting groups
Overall Number of Baseline Participants		280	280	560
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	112 40.0%	95 33.9%	207 37.0%
	Unknown or Not Reported	165 58.9%	183 65.4%	348 62.1%
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

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
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

Outcome Measure Data

Analysis Population Description

All Randomized Participants: All enrolled Participants who were randomized to any treatment arm.

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description:	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab + Radiation Therapy, Temozolomide + Radiation Therapy
	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	Kaplan-Meier Plot of Progression Free Survival
Description	PFS was 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 were 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 were censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression were 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 were censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on the Radiologic Assessment in Neuro-Oncology criteria.
Time Frame	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description:	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
Overall Number of Participants Analyzed	280	280
Median (95% Confidence Interval); Unit of Measure: Months
	6.01; (5.65 to 6.21)	6.21; (5.98 to 6.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab + Radiation Therapy, Temozolomide + Radiation Therapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Hazard Ratio is Nivolumab over Temozolomide
Statistical Test of Hypothesis	P-Value	[Not Specified]
	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	1.43
	Confidence Interval	(2-Sided) 95%; 1.19 to 1.71
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival Rate at 24 Months
Description	The overall survival (OS) rate of (nivolumab + radiation therapy) and (temozolomide + radiation therapy) estimated as Kaplan-Meier probability of survival at 24 months. OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date.
Time Frame	At 24 Months

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description:	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
Overall Number of Participants Analyzed	280	280
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	10.6; (7.3 to 14.6)	21.2; (16.5 to 26.3)

4. Secondary Outcome

Title	Overall Survival in Tumor Mutational Burden (TMB) High Population
Description	OS in all randomized participants that are tumor mutational burden high. OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date.
Time Frame	From randomization to the date of death due to any cause (up to approximately 6 years)

Outcome Measure Data

Analysis Population Description

Data was not and will never be collected

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description:	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

5. Secondary Outcome

Title	Progression Free Survival in Tumor Mutational Burden (TMB) High Population
Description	PFS in all randomized participants that are tumor mutational burden high. PFS was 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 were 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 were censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression were 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 were censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on the Radiologic Assessment in Neuro-Oncology criteria.
Time Frame	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)

Outcome Measure Data

Analysis Population Description

Data was not and will never be collected

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description:	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Post-Hoc Outcome

Title	Kaplan-Meier Plot of Overall Survival (OS) - Extended Collection
Description	OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date (assessments were made until March 4, 2022).
Time Frame	From randomization to the date of death due to any cause (up to approximately 6 years)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description:	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
Overall Number of Participants Analyzed	280	280
Median (95% Confidence Interval); Unit of Measure: Months
	13.34; (12.55 to 14.16)	14.92; (13.27 to 16.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab + Radiation Therapy, Temozolomide + Radiation Therapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Hazard Ratio is Nivolumab over Temozolomide
Statistical Test of Hypothesis	P-Value	0.0024
	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%; 1.10 to 1.55
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	All-cause mortality was assessed from the participant's randomization to their study completion (up to approximately 6 years). SAEs and Other AEs were assessed from first dose to 100 days after last dose of study therapy (up to approximately 67 months).
Adverse Event Reporting Description	The total number at risk for all-cause mortality represents all participants who were randomized. The total number at risk by any serious adverse event and other (not including serious) adverse events represents all participants that received at least 1 dose of study medication.
Arm/Group Title	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
Arm/Group Description	Nivolumab 240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks administered intravenously	Temozolomide 75 mg/m2 daily during radiation therapy, then 150 mg/m2 Days 1-5 for Cycle 1, then increased to 200 mg/m2 Days 1-5 for Cycles 2-6 administered orally
All-Cause Mortality
	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	269/280 (96.07%)	253/280 (90.36%)
Serious Adverse Events
	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	206/278 (74.10%)	141/275 (51.27%)
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%)
Visual field defect † 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%)
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	6/278 (2.16%)	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
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-mediated hepatitis † 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%)
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%)
Meningitis † 1	1/278 (0.36%)	0/275 (0.00%)
Meningitis aseptic † 1	2/278 (0.72%)	0/275 (0.00%)
Peritonitis † 1	0/278 (0.00%)	1/275 (0.36%)
Pneumonia † 1	6/278 (2.16%)	2/275 (0.73%)
Pneumonia aspiration † 1	2/278 (0.72%)	0/275 (0.00%)
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%)
Pelvic fracture † 1	0/278 (0.00%)	1/275 (0.36%)
Pseudomeningocele † 1	1/278 (0.36%)	0/275 (0.00%)
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%)
General physical condition abnormal † 1	1/278 (0.36%)	0/275 (0.00%)
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%)
Myalgia † 1	1/278 (0.36%)	0/275 (0.00%)
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	89/278 (32.01%)	57/275 (20.73%)
Metastases to meninges † 1	1/278 (0.36%)	1/275 (0.36%)
Neoplasm † 1	2/278 (0.72%)	0/275 (0.00%)
Neoplasm malignant † 1	1/278 (0.36%)	0/275 (0.00%)
Neoplasm progression † 1	6/278 (2.16%)	3/275 (1.09%)
Recurrent cancer † 1	0/278 (0.00%)	1/275 (0.36%)
Tumour flare † 1	15/278 (5.40%)	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	11/278 (3.96%)	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%)
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%)
Immune-mediated lung disease † 1	1/278 (0.36%)	0/275 (0.00%)
Interstitial lung disease † 1	1/278 (0.36%)	0/275 (0.00%)
Lung consolidation † 1	0/278 (0.00%)	1/275 (0.36%)
Pneumonitis † 1	1/278 (0.36%)	0/275 (0.00%)
Pulmonary embolism † 1	7/278 (2.52%)	10/275 (3.64%)
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
Euthanasia † 1	0/278 (0.00%)	1/275 (0.36%)
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, 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab + Radiation Therapy	Temozolomide + Radiation Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	262/278 (94.24%)	259/275 (94.18%)
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
Dry eye † 1	14/278 (5.04%)	3/275 (1.09%)
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	54/278 (19.42%)	80/275 (29.09%)
Diarrhoea † 1	44/278 (15.83%)	23/275 (8.36%)
Nausea † 1	66/278 (23.74%)	105/275 (38.18%)
Vomiting † 1	35/278 (12.59%)	63/275 (22.91%)
General disorders
Asthenia † 1	25/278 (8.99%)	27/275 (9.82%)
Fatigue † 1	123/278 (44.24%)	128/275 (46.55%)
Gait disturbance † 1	24/278 (8.63%)	7/275 (2.55%)
Malaise † 1	14/278 (5.04%)	13/275 (4.73%)
Oedema peripheral † 1	17/278 (6.12%)	15/275 (5.45%)
Pyrexia † 1	30/278 (10.79%)	16/275 (5.82%)
Infections and infestations
Nasopharyngitis † 1	21/278 (7.55%)	13/275 (4.73%)
Urinary tract infection † 1	23/278 (8.27%)	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	20/278 (7.19%)	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%)	50/275 (18.18%)
Hyperglycaemia † 1	15/278 (5.40%)	9/275 (3.27%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	25/278 (8.99%)	13/275 (4.73%)
Back pain † 1	17/278 (6.12%)	17/275 (6.18%)
Muscular weakness † 1	15/278 (5.40%)	12/275 (4.36%)
Nervous system disorders
Aphasia † 1	30/278 (10.79%)	20/275 (7.27%)
Cognitive disorder † 1	14/278 (5.04%)	12/275 (4.36%)
Dizziness † 1	41/278 (14.75%)	19/275 (6.91%)
Dysgeusia † 1	14/278 (5.04%)	16/275 (5.82%)
Headache † 1	115/278 (41.37%)	96/275 (34.91%)
Hemiparesis † 1	24/278 (8.63%)	12/275 (4.36%)
Memory impairment † 1	19/278 (6.83%)	14/275 (5.09%)
Seizure † 1	35/278 (12.59%)	36/275 (13.09%)
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%)	14/275 (5.09%)
Depression † 1	22/278 (7.91%)	12/275 (4.36%)
Insomnia † 1	29/278 (10.43%)	18/275 (6.55%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	21/278 (7.55%)	11/275 (4.00%)
Skin and subcutaneous tissue disorders
Alopecia † 1	73/278 (26.26%)	88/275 (32.00%)
Pruritus † 1	31/278 (11.15%)	22/275 (8.00%)
Rash † 1	40/278 (14.39%)	18/275 (6.55%)
Vascular disorders
Hypertension † 1	16/278 (5.76%)	12/275 (4.36%)
1 Term from vocabulary, 24.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please Email
• EMail: Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol. 2020 Sep 29;22(9):1233-1234. doi: 10.1093/neuonc/noaa170. No abstract available.

• 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: March 28, 2023