CheckMate 498: 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)

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT02617589

Collaborator

Ono Pharmaceutical Co. Ltd (Industry)

560

Enrollment

125

Locations

Arms

72.1

Actual Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate patients with glioblastoma that is MGMT-unmethylated (the MGMT gene is not altered by a chemical change). Patients will receive Nivolumab every two weeks in addition to radiation therapy, and then every four weeks. They will be compared to patients receiving standard therapy with temozolomide in addition to radiation therapy.

Condition or Disease	Intervention/Treatment	Phase
Brain Cancer	Drug: Nivolumab Drug: Temozolomide Radiation: Radiotherapy	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

560 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase 3 Open Label Study of Nivolumab vs Temozolomide Each in Combination With Radiation Therapy in Newly Diagnosed Adult Subjects With Unmethylated MGMT (Tumor O-6-methylguanine DNA Methyltransferase) Glioblastoma (CheckMate 498: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 498)

Actual Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Jan 17, 2019

Actual Study Completion Date :

Mar 4, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab + Radiotherapy Arm Nivolumab IV infusion + Radiotherapy dose as specified	Drug: Nivolumab Radiation: Radiotherapy
Active Comparator: Temozolomide + Radiotherapy Arm Temozolomide + Radiotherapy dose as specified	Drug: Temozolomide Radiation: Radiotherapy

Arm

Intervention/Treatment

Experimental: Nivolumab + Radiotherapy Arm

Nivolumab IV infusion + Radiotherapy dose as specified

Drug: Nivolumab

Radiation: Radiotherapy

Active Comparator: Temozolomide + Radiotherapy Arm

Temozolomide + Radiotherapy dose as specified

Drug: Temozolomide

Radiation: Radiotherapy

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [up to 3 years]
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.

Secondary Outcome Measures

Progression Free Survival (PFS) [up to 3 years]
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
OS at 24 Months [at 24 Months]
The OS rate at 24 months of nivolumab + RT and RT + TMZ was estimated as Kaplan-Meier probability of survival at 24 months.
OS in Tumor Mutational Burden (TMB) High Population [up to 3 years]
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.
PFS in Tumor Mutational Burden (TMB) High Population [up to 3 years]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and Females, age ≥ 18 years old
Newly-diagnosed brain cancer or tumor called glioblastoma or GBM
Tumor test result shows MGMT unmethylated type
Karnofsky performance status of ≥ 70 (able to care for self)

Exclusion Criteria:

Prior treatment for GBM (other than surgical resection)
Any known tumor outside of the brain
Recurrent or secondary GBM
Active known or suspected autoimmune disease
Biopsy with less than 20% of tumor removed

Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3410
2	St. Joseph Hospital And Medical Center	Phoenix	Arizona	United States	85013
3	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
4	UCLA Neuro-Oncology Program	Los Angeles	California	United States	90095-1769
5	Sutter Institute For Medical Research	Sacramento	California	United States	95816
6	Sharp Memorial Hospital	San Diego	California	United States	92123
7	The Regents of the University of California, San Francisco	San Francisco	California	United States	94143-0372
8	Yale Cancer Center	New Haven	Connecticut	United States	06520
9	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
10	University Of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
11	Moffitt Cancer Center	Tampa	Florida	United States	33612
12	Emory University - Winship Cancer Institute	Atlanta	Georgia	United States	30322
13	The University Of Chicago	Chicago	Illinois	United States	60637
14	University Of Kansas Medical Center	Westwood	Kansas	United States	66205
15	Norton Cancer Institute	Louisville	Kentucky	United States	40202
16	Johns Hopkins University School Of Medicine	Baltimore	Maryland	United States	21287
17	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02215
19	Henry Ford Health System	Detroit	Michigan	United States	48202
20	Washington University School OF Medicine-Siteman Cancer Center	Saint Louis	Missouri	United States	63110
21	JFK Medical Center	Edison	New Jersey	United States	08820
22	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
23	Columbia University Medical Center (Cumc)	New York	New York	United States	10032
24	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
25	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
26	Preston Robert Tisch Brain Tumor Center at Duke University	Durham	North Carolina	United States	27710
27	Cleveland Clinic	Cleveland	Ohio	United States	44195
28	The Ohio State University	Columbus	Ohio	United States	43210
29	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
30	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
31	Medical University Of South Carolina	Charleston	South Carolina	United States	29425
32	Erlanger Oncology & Hematology - Univ. of TN	Chattanooga	Tennessee	United States	37404
33	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
34	University Of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-8852
35	University Of Texas Md Anderson Cancer Ctr	Houston	Texas	United States	77030
36	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
37	Swedish Neuroscience Institute	Seattle	Washington	United States	98122
38	Royal North Shore Hospital	St. Leonards	New South Wales	Australia	2065
39	Local Institution	Heidelberg	Victoria	Australia	3084
40	Local Institution	Prahran	Victoria	Australia	3181
41	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
42	Local Institution	New South Wales		Australia	2170
43	Kepler Universitaetsklinikum	Linz		Austria	4020
44	Medical University Of Vienna	Vienna		Austria	1090
45	Universitair Ziekenhuis Brussel	Brussels		Belgium	1090
46	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
47	Uz Leuven	Leuven		Belgium	3000
48	BC Cancer - Vancouver	Vancouver	British Columbia	Canada	V5Z 4E6
49	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
50	Montreal Neurological Institute and Hospital	Montreal	Quebec	Canada	H3A 2B4
51	Local Institution	Copenhagen		Denmark	2100
52	Local Institution	Odense		Denmark	5000
53	Hopital Neurologique Pierre Wertheimer	Bron Cedex		France	69677
54	Local Institution	Lille Cedex		France	59037
55	Hopital La Timone	Marseille		France	13005
56	Hopital Central	Nancy		France	54035
57	Groupe Hospitalier Pitie-Salpetriere	Paris cedex 13		France	75651
58	Local Institution	Paris		France	75010
59	Centre Eugene Marquis	Rennes		France	35000
60	Institut Univ Cancer Toulouse	Toulouse		France	31100
61	Universitaetsklinikum Bonn	Bonn		Germany	53105
62	Uniklinik Erlangen	Erlangen		Germany	91054
63	Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main	Frankfurt am Main		Germany	60528
64	Medizinische Universitaetsklinik Freiburg	Freiburg		Germany	79106
65	Universitaetsklinikum Hamburg	Hamburg		Germany	20246
66	Universitaetsklinik Heidelberg	Heidelberg		Germany	69120
67	Universitaetsklinikum Koeln	Koeln		Germany	50937
68	Universitaetsklinikum Muenster	Muenster		Germany	48149
69	Klinikum rechts der Isar der Technischen Universitat Munchen	Munich		Germany	81675
70	Universitaetsklinikum Regensburg	Regensburg		Germany	93053
71	Universitasklinikum Tubingen	Tuebingen		Germany	72076
72	Local Institution	Petach Tikva		Israel	49100
73	Local Institution	Tel Aviv		Israel	64239
74	Local Institution	Bologna		Italy	40139
75	Local Institution	Milano		Italy	20133
76	Local Institution	Padova		Italy	35128
77	Local Institution	Rozzano (milano)		Italy	20089
78	Local Institution	Siena		Italy	53100
79	Azienda Ospedaliera Citta della Salute e della Scienza	Torino		Italy	10126
80	Local Institution	Nagoya-shi	Aichi	Japan	4668560
81	Local Institution	Chiba-shi	Chiba	Japan	2608677
82	Local Institution	Hiroshima-Shi	Hiroshima	Japan	7348551
83	Local Institution	Sapporo-shi	Hokkaido	Japan	0608648
84	Local Institution	Kobe	Hyogo	Japan	6500017
85	Local Institution	Tsukuba-shi	Ibaraki	Japan	3058576
86	Local Institution	Kanazawa-shi	Ishikawa	Japan	9200934
87	Local Institution	Kagoshima-shi	Kagoshima	Japan	8908520
88	Local Institution	Sagamihara-shi	Kanagawa	Japan	2520375
89	Local Institution	Kumamoto-shi	Kumamoto	Japan	8608556
90	Local Institution	Kyoto-shi	Kyoto	Japan	606-8507
91	Local Institution	Kyoto-shi	Kyoto	Japan	6128555
92	Local Institution	Okayama-shi	Okayama	Japan	7008558
93	Local Institution	Hirakata-shi	Osaka	Japan	5731191
94	Local Institution	Suita-shi	Osaka	Japan	5650871
95	Local Institution	Hidaka	Saitama	Japan	350-1298
96	Local Institution	Bunkyo-ku	Tokyo	Japan	1138655
97	Local Institution	Chuo-ku	Tokyo	Japan	1040045
98	Local Institution	Mitaka-shi	Tokyo	Japan	181-8611
99	Local Institution	Yamagata-shi	Yamagata	Japan	9909585
100	Local Institution	Tokyo		Japan	1628666
101	NKI AVL	Amsterdam		Netherlands	1066 CX
102	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 AP
103	Erasmus Mc	Rotterdam		Netherlands	3015 CE
104	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584CX
105	Local Institution	Oslo		Norway	0379
106	Uniwersyteckie Centrum Kliniczne Klinika Onkologii I Radiote	Gdansk		Poland	80952
107	Local Institution	Warszawa		Poland	02-781
108	Local Institution	Moscow		Russian Federation	105229
109	Local Institution	Moscow		Russian Federation	115478
110	Local Institution	Badalona-Barcelona		Spain	08916
111	Local Institution	Barcelona		Spain	08035
112	Local Institution	Barcelona		Spain	08036
113	Local Institution	Madrid		Spain	28007
114	Local Institution	Madrid		Spain	28041
115	Local Institution	Santiago De Compostela		Spain	15706
116	Local Institution	Valencia		Spain	46014
117	Local Institution	Lund		Sweden	221 85
118	Local Institution	Solna		Sweden	171 64
119	University Hospital Geneva	Geneve		Switzerland	1211
120	Centre hospitalier universitaire Vaudois (CHUV)	Lausanne		Switzerland	1011
121	Universitaetsspital Zuerich	Zuerich		Switzerland	8091
122	University College Hospital	London	Greater London	United Kingdom	NW1 2PG
123	Christie Hospital Nhs Found. Trust	Manchester	Greater Manchester	United Kingdom	M20 4BX
124	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
125	Beaston West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN

Sponsors and Collaborators

Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd

Investigators

Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.

Responsible Party:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT02617589

Other Study ID Numbers:

CA209-498
2015-003739-37

First Posted:

Dec 1, 2015

Last Update Posted:

Mar 29, 2022

Last Verified:

Mar 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	560 Randomized and treated.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	nivolumab + radiation therapy(RT)	temozolomide (TMZ) + radiation therapy
Period Title: All Randomized
STARTED	280	280
COMPLETED	278	275
NOT COMPLETED	2	5
Period Title: All Randomized
STARTED	278	275
COMPLETED	4	1
NOT COMPLETED	274	274

Baseline Characteristics

Arm/Group Title	Treatment A	Treatment B	Total
Arm/Group Description	nivolumab + radiation therapy(RT)	temozolomide (TMZ) + radiation therapy	Total of all reporting groups
Overall Participants	280	280	560
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.8 (10.8)	56.5 (11.3)	57.6 (11.1)
Sex: Female, Male (Count of Participants)
Female	90 32.1%	105 37.5%	195 34.8%
Male	190 67.9%	175 62.5%	365 65.2%
Ethnicity (NIH/OMB) (Count of 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%
Race/Ethnicity, Customized (Number) [Number]
White	231 82.5%	240 85.7%	471 84.1%
Black or African American	4 1.4%	3 1.1%	7 1.3%
Asian	33 11.8%	28 10%	61 10.9%
Other	12 4.3%	9 3.2%	21 3.8%

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	Treatment A	Treatment B
Arm/Group Description	nivolumab + radiation Therapy	temozolomide (TMZ) + radiation therapy
Measure Participants	280	280
Median (95% Confidence Interval) [Months]	13.40	14.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority
	Comments	Hazard Ratio is Nivolumab over Temozolomide

Statistical Test of Hypothesis	p-Value	0.0037
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
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

Outcome Measure Data

Analysis Population Description
All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	nivolumab + radiation Therapy	temozolomide (TMZ) + radiation therapy
Measure Participants	280	280
Median (95% Confidence Interval) [Months]	6.01	6.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority
	Comments	Hazard Ratio is Nivolumab over Temozolomide

Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	OS at 24 Months
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

Outcome Measure Data

Analysis Population Description
All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	nivolumab + radiation Therapy	temozolomide (TMZ) + radiation therapy
Measure Participants	280	280
Number (95% Confidence Interval) [Percentage of Survival]	10.3	21.2

4. Secondary Outcome

Title	OS in Tumor Mutational Burden (TMB) High Population
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
TMB-High Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	nivolumab + radiation Therapy	temozolomide (TMZ) + radiation therapy
Measure Participants	280	280
Median (95% Confidence Interval) [Months]	NA	NA

5. Secondary Outcome

Title	PFS in Tumor Mutational Burden (TMB) High Population
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

Outcome Measure Data

Analysis Population Description
TMB-High Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	nivolumab + radiation Therapy	temozolomide (TMZ) + radiation therapy
Measure Participants	280	280
Median (95% Confidence Interval) [Months]	NA	NA

Adverse Events

	Treatment A		Treatment B
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

Arm/Group Title	Treatment A		Treatment B
Arm/Group Description	nivolumab + radiation Therapy		temozolomide (TMZ) + radiation therapy
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	242/278 (87.1%)		216/275 (78.5%)
Serious Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	205/278 (73.7%)		140/275 (50.9%)
Blood and lymphatic system disorders
Agranulocytosis	2/278 (0.7%)		0/275 (0%)
Febrile neutropenia	0/278 (0%)		1/275 (0.4%)
Leukopenia	0/278 (0%)		1/275 (0.4%)
Lymphopenia	0/278 (0%)		1/275 (0.4%)
Neutropenia	1/278 (0.4%)		2/275 (0.7%)
Thrombocytopenia	1/278 (0.4%)		8/275 (2.9%)
Cardiac disorders
Arrhythmia	0/278 (0%)		1/275 (0.4%)
Atrial fibrillation	0/278 (0%)		2/275 (0.7%)
Cardiac arrest	1/278 (0.4%)		0/275 (0%)
Stress cardiomyopathy	0/278 (0%)		1/275 (0.4%)
Endocrine disorders
Hypophysitis	1/278 (0.4%)		0/275 (0%)
Hypothyroidism	1/278 (0.4%)		0/275 (0%)
Eye disorders
Retinal detachment	1/278 (0.4%)		0/275 (0%)
Gastrointestinal disorders
Abdominal pain	1/278 (0.4%)		0/275 (0%)
Constipation	0/278 (0%)		2/275 (0.7%)
Diarrhoea	5/278 (1.8%)		1/275 (0.4%)
Gastrointestinal inflammation	0/278 (0%)		1/275 (0.4%)
Gastrointestinal perforation	1/278 (0.4%)		0/275 (0%)
Ileus	1/278 (0.4%)		0/275 (0%)
Inguinal hernia	1/278 (0.4%)		0/275 (0%)
Intestinal obstruction	0/278 (0%)		1/275 (0.4%)
Nausea	1/278 (0.4%)		4/275 (1.5%)
Oesophagitis	1/278 (0.4%)		0/275 (0%)
Pancreatitis	1/278 (0.4%)		0/275 (0%)
Pancreatitis acute	0/278 (0%)		1/275 (0.4%)
Vomiting	5/278 (1.8%)		2/275 (0.7%)
General disorders
Adverse event	1/278 (0.4%)		1/275 (0.4%)
Asthenia	1/278 (0.4%)		1/275 (0.4%)
Condition aggravated	0/278 (0%)		2/275 (0.7%)
Disease progression	3/278 (1.1%)		0/275 (0%)
Euthanasia	0/278 (0%)		1/275 (0.4%)
Fatigue	2/278 (0.7%)		1/275 (0.4%)
Gait disturbance	2/278 (0.7%)		0/275 (0%)
General physical health deterioration	7/278 (2.5%)		3/275 (1.1%)
Impaired healing	1/278 (0.4%)		0/275 (0%)
Malaise	3/278 (1.1%)		0/275 (0%)
Multiple organ dysfunction syndrome	2/278 (0.7%)		0/275 (0%)
Polyserositis	1/278 (0.4%)		0/275 (0%)
Pyrexia	7/278 (2.5%)		2/275 (0.7%)
Sudden death	2/278 (0.7%)		1/275 (0.4%)
Hepatobiliary disorders
Autoimmune hepatitis	1/278 (0.4%)		0/275 (0%)
Cholecystitis acute	0/278 (0%)		1/275 (0.4%)
Drug-induced liver injury	3/278 (1.1%)		0/275 (0%)
Hepatic function abnormal	2/278 (0.7%)		0/275 (0%)
Hepatitis	1/278 (0.4%)		0/275 (0%)
Hepatotoxicity	1/278 (0.4%)		0/275 (0%)
Immune system disorders
Autoimmune disorder	1/278 (0.4%)		0/275 (0%)
Infections and infestations
Anal abscess	0/278 (0%)		1/275 (0.4%)
Appendicitis	0/278 (0%)		1/275 (0.4%)
Brain abscess	1/278 (0.4%)		0/275 (0%)
Bronchitis	1/278 (0.4%)		1/275 (0.4%)
Encephalitis	0/278 (0%)		1/275 (0.4%)
Gastroenteritis viral	0/278 (0%)		1/275 (0.4%)
Hepatitis viral	1/278 (0.4%)		0/275 (0%)
Herpes zoster	0/278 (0%)		1/275 (0.4%)
Lung infection	1/278 (0.4%)		0/275 (0%)
Meningitis	1/278 (0.4%)		1/275 (0.4%)
Meningitis aseptic	2/278 (0.7%)		0/275 (0%)
Pneumonia	6/278 (2.2%)		2/275 (0.7%)
Postoperative wound infection	0/278 (0%)		1/275 (0.4%)
Respiratory tract infection	1/278 (0.4%)		0/275 (0%)
Sepsis	1/278 (0.4%)		0/275 (0%)
Skin infection	2/278 (0.7%)		0/275 (0%)
Staphylococcal infection	0/278 (0%)		1/275 (0.4%)
Upper respiratory tract infection	0/278 (0%)		1/275 (0.4%)
Urinary tract infection	1/278 (0.4%)		2/275 (0.7%)
Urosepsis	0/278 (0%)		1/275 (0.4%)
Wound infection	2/278 (0.7%)		1/275 (0.4%)
Injury, poisoning and procedural complications
Accidental overdose	0/278 (0%)		1/275 (0.4%)
Compression fracture	0/278 (0%)		1/275 (0.4%)
Fall	3/278 (1.1%)		1/275 (0.4%)
Femur fracture	0/278 (0%)		1/275 (0.4%)
Head injury	1/278 (0.4%)		0/275 (0%)
Humerus fracture	1/278 (0.4%)		0/275 (0%)
Infusion related reaction	1/278 (0.4%)		0/275 (0%)
Pseudomeningocele	1/278 (0.4%)		0/275 (0%)
Pubis fracture	0/278 (0%)		1/275 (0.4%)
Spinal compression fracture	1/278 (0.4%)		1/275 (0.4%)
Spinal fracture	0/278 (0%)		1/275 (0.4%)
Subdural haematoma	2/278 (0.7%)		1/275 (0.4%)
Wound	0/278 (0%)		1/275 (0.4%)
Wound dehiscence	1/278 (0.4%)		0/275 (0%)
Investigations
Alanine aminotransferase increased	0/278 (0%)		1/275 (0.4%)
Aspartate aminotransferase increased	0/278 (0%)		1/275 (0.4%)
Blood creatinine increased	1/278 (0.4%)		0/275 (0%)
Blood glucose increased	0/278 (0%)		1/275 (0.4%)
Fibrin D dimer increased	0/278 (0%)		1/275 (0.4%)
Hepatic enzyme increased	1/278 (0.4%)		0/275 (0%)
Platelet count decreased	0/278 (0%)		4/275 (1.5%)
Transaminases increased	0/278 (0%)		1/275 (0.4%)
Troponin increased	1/278 (0.4%)		0/275 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/278 (1.1%)		0/275 (0%)
Hyperglycaemia	5/278 (1.8%)		2/275 (0.7%)
Hypernatraemia	0/278 (0%)		1/275 (0.4%)
Hyponatraemia	4/278 (1.4%)		1/275 (0.4%)
Metabolic acidosis	1/278 (0.4%)		0/275 (0%)
Steroid diabetes	0/278 (0%)		1/275 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/278 (0.4%)		1/275 (0.4%)
Fistula	1/278 (0.4%)		0/275 (0%)
Muscular weakness	1/278 (0.4%)		4/275 (1.5%)
Myopathy	1/278 (0.4%)		0/275 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma	6/278 (2.2%)		0/275 (0%)
Glioblastoma multiforme	1/278 (0.4%)		0/275 (0%)
Malignant neoplasm progression	86/278 (30.9%)		54/275 (19.6%)
Metastases to meninges	1/278 (0.4%)		0/275 (0%)
Neoplasm	2/278 (0.7%)		0/275 (0%)
Neoplasm malignant	1/278 (0.4%)		0/275 (0%)
Neoplasm progression	4/278 (1.4%)		3/275 (1.1%)
Recurrent cancer	0/278 (0%)		1/275 (0.4%)
Tumour flare	14/278 (5%)		0/275 (0%)
Tumour pseudoprogression	2/278 (0.7%)		1/275 (0.4%)
Nervous system disorders
Aphasia	4/278 (1.4%)		3/275 (1.1%)
Ataxia	2/278 (0.7%)		0/275 (0%)
Brain oedema	6/278 (2.2%)		8/275 (2.9%)
Cerebellar stroke	1/278 (0.4%)		0/275 (0%)
Cerebral haemorrhage	1/278 (0.4%)		1/275 (0.4%)
Cerebral ischaemia	1/278 (0.4%)		1/275 (0.4%)
Cerebrospinal fluid leakage	0/278 (0%)		1/275 (0.4%)
Depressed level of consciousness	1/278 (0.4%)		1/275 (0.4%)
Dizziness	2/278 (0.7%)		0/275 (0%)
Encephalopathy	4/278 (1.4%)		1/275 (0.4%)
Epilepsy	9/278 (3.2%)		11/275 (4%)
Generalised tonic-clonic seizure	0/278 (0%)		2/275 (0.7%)
Haemorrhage intracranial	2/278 (0.7%)		1/275 (0.4%)
Headache	12/278 (4.3%)		5/275 (1.8%)
Hemianopia	0/278 (0%)		1/275 (0.4%)
Hemiparesis	9/278 (3.2%)		6/275 (2.2%)
Hydrocephalus	2/278 (0.7%)		1/275 (0.4%)
IIIrd nerve disorder	0/278 (0%)		1/275 (0.4%)
Intracranial pressure increased	2/278 (0.7%)		3/275 (1.1%)
Ischaemic stroke	1/278 (0.4%)		0/275 (0%)
Lethargy	1/278 (0.4%)		1/275 (0.4%)
Loss of consciousness	0/278 (0%)		1/275 (0.4%)
Migraine	1/278 (0.4%)		0/275 (0%)
Nervous system disorder	1/278 (0.4%)		2/275 (0.7%)
Neurological decompensation	1/278 (0.4%)		1/275 (0.4%)
Neurological symptom	1/278 (0.4%)		0/275 (0%)
Paraesthesia	1/278 (0.4%)		0/275 (0%)
Partial seizures	4/278 (1.4%)		1/275 (0.4%)
Seizure	37/278 (13.3%)		30/275 (10.9%)
Subdural hygroma	0/278 (0%)		1/275 (0.4%)
Syncope	1/278 (0.4%)		0/275 (0%)
Transient ischaemic attack	1/278 (0.4%)		0/275 (0%)
Vasogenic cerebral oedema	2/278 (0.7%)		0/275 (0%)
Visual field defect	1/278 (0.4%)		0/275 (0%)
Psychiatric disorders
Agitation	2/278 (0.7%)		0/275 (0%)
Anxiety	0/278 (0%)		1/275 (0.4%)
Apathy	1/278 (0.4%)		0/275 (0%)
Confusional state	3/278 (1.1%)		4/275 (1.5%)
Drug dependence	0/278 (0%)		1/275 (0.4%)
Major depression	1/278 (0.4%)		0/275 (0%)
Mental status changes	3/278 (1.1%)		0/275 (0%)
Mood altered	1/278 (0.4%)		0/275 (0%)
Personality change	1/278 (0.4%)		0/275 (0%)
Suicidal ideation	0/278 (0%)		1/275 (0.4%)
Renal and urinary disorders
Acute kidney injury	2/278 (0.7%)		0/275 (0%)
Haematuria	1/278 (0.4%)		0/275 (0%)
Nephrolithiasis	0/278 (0%)		1/275 (0.4%)
Urinary incontinence	1/278 (0.4%)		0/275 (0%)
Urinary retention	1/278 (0.4%)		0/275 (0%)
Reproductive system and breast disorders
Testicular disorder	1/278 (0.4%)		0/275 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/278 (0.4%)		0/275 (0%)
Chronic obstructive pulmonary disease	1/278 (0.4%)		0/275 (0%)
Dyspnoea	0/278 (0%)		1/275 (0.4%)
Hiccups	0/278 (0%)		1/275 (0.4%)
Interstitial lung disease	1/278 (0.4%)		0/275 (0%)
Lung consolidation	0/278 (0%)		1/275 (0.4%)
Pneumonia aspiration	2/278 (0.7%)		0/275 (0%)
Pneumonitis	1/278 (0.4%)		0/275 (0%)
Pulmonary embolism	7/278 (2.5%)		9/275 (3.3%)
Respiratory failure	2/278 (0.7%)		1/275 (0.4%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised	1/278 (0.4%)		0/275 (0%)
Rash	3/278 (1.1%)		1/275 (0.4%)
Rash macular	1/278 (0.4%)		0/275 (0%)
Rash maculo-papular	2/278 (0.7%)		2/275 (0.7%)
Skin toxicity	1/278 (0.4%)		0/275 (0%)
Surgical and medical procedures
Cranioplasty	0/278 (0%)		1/275 (0.4%)
Surgery	1/278 (0.4%)		0/275 (0%)
Vascular disorders
Deep vein thrombosis	1/278 (0.4%)		5/275 (1.8%)
Embolism	6/278 (2.2%)		2/275 (0.7%)
Haematoma	1/278 (0.4%)		2/275 (0.7%)
Venous thrombosis	0/278 (0%)		1/275 (0.4%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	261/278 (93.9%)		258/275 (93.8%)
Blood and lymphatic system disorders
Anaemia	16/278 (5.8%)		11/275 (4%)
Lymphopenia	7/278 (2.5%)		24/275 (8.7%)
Neutropenia	1/278 (0.4%)		16/275 (5.8%)
Thrombocytopenia	4/278 (1.4%)		26/275 (9.5%)
Endocrine disorders
Hypothyroidism	18/278 (6.5%)		2/275 (0.7%)
Eye disorders
Vision blurred	16/278 (5.8%)		4/275 (1.5%)
Gastrointestinal disorders
Abdominal pain	16/278 (5.8%)		7/275 (2.5%)
Constipation	53/278 (19.1%)		79/275 (28.7%)
Diarrhoea	45/278 (16.2%)		23/275 (8.4%)
Nausea	66/278 (23.7%)		105/275 (38.2%)
Vomiting	35/278 (12.6%)		62/275 (22.5%)
General disorders
Asthenia	24/278 (8.6%)		25/275 (9.1%)
Fatigue	121/278 (43.5%)		126/275 (45.8%)
Gait disturbance	23/278 (8.3%)		6/275 (2.2%)
Malaise	14/278 (5%)		13/275 (4.7%)
Oedema peripheral	16/278 (5.8%)		15/275 (5.5%)
Pyrexia	30/278 (10.8%)		16/275 (5.8%)
Infections and infestations
Nasopharyngitis	20/278 (7.2%)		13/275 (4.7%)
Urinary tract infection	24/278 (8.6%)		14/275 (5.1%)
Injury, poisoning and procedural complications
Fall	14/278 (5%)		13/275 (4.7%)
Radiation skin injury	30/278 (10.8%)		23/275 (8.4%)
Investigations
Alanine aminotransferase increased	23/278 (8.3%)		20/275 (7.3%)
Lymphocyte count decreased	15/278 (5.4%)		32/275 (11.6%)
Neutrophil count decreased	3/278 (1.1%)		18/275 (6.5%)
Platelet count decreased	8/278 (2.9%)		41/275 (14.9%)
Weight decreased	19/278 (6.8%)		20/275 (7.3%)
White blood cell count decreased	6/278 (2.2%)		15/275 (5.5%)
Metabolism and nutrition disorders
Decreased appetite	33/278 (11.9%)		49/275 (17.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/278 (7.2%)		11/275 (4%)
Back pain	18/278 (6.5%)		17/275 (6.2%)
Nervous system disorders
Aphasia	29/278 (10.4%)		18/275 (6.5%)
Cognitive disorder	14/278 (5%)		11/275 (4%)
Dizziness	40/278 (14.4%)		19/275 (6.9%)
Dysgeusia	18/278 (6.5%)		17/275 (6.2%)
Headache	113/278 (40.6%)		95/275 (34.5%)
Hemiparesis	24/278 (8.6%)		11/275 (4%)
Memory impairment	19/278 (6.8%)		13/275 (4.7%)
Seizure	35/278 (12.6%)		34/275 (12.4%)
Somnolence	19/278 (6.8%)		8/275 (2.9%)
Psychiatric disorders
Anxiety	18/278 (6.5%)		9/275 (3.3%)
Confusional state	23/278 (8.3%)		13/275 (4.7%)
Depression	23/278 (8.3%)		12/275 (4.4%)
Insomnia	29/278 (10.4%)		18/275 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	20/278 (7.2%)		11/275 (4%)
Skin and subcutaneous tissue disorders
Alopecia	73/278 (26.3%)		88/275 (32%)
Pruritus	30/278 (10.8%)		22/275 (8%)
Rash	40/278 (14.4%)		17/275 (6.2%)
Vascular disorders
Hypertension	17/278 (6.1%)		12/275 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

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

Responsible Party:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT02617589

Other Study ID Numbers:

CA209-498
2015-003739-37

First Posted:

Dec 1, 2015

Last Update Posted:

Mar 29, 2022

Last Verified:

Mar 1, 2022

CheckMate 498: 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)

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact