CheckMate 384: A Dose Frequency Optimization,Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received Up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02713867
• Collaborator: (none)
• Enrollment: 363
• Locations: 119
• Arms: 2
• Actual Duration (Months): 67.8
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare PFS (progression-free survival) rate at 6 months and at 1 year after randomization, of Nivolumab 480 mg every 4 weeks with nivolumab 240 mg every 2 weeks in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: Nivolumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 363 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Dose Frequency Optimization, Phase IIIB/IV Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks
• Actual Study Start Date: May 24, 2016
• Actual Primary Completion Date: Jul 15, 2019
• Actual Study Completion Date: Jan 18, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nivolumab 240 mg Nivolumab 240 mg Every 2 Weeks	Biological: Nivolumab
Experimental: Nivolumab 480 mg Nivolumab 480 mg Every 4 Weeks	Biological: Nivolumab

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival Rate(PFSR) at 6 Months [at 6 Months]

   PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.

2. Progression Free Survival Rate (PFSR) at 12 Months [at 12 Months]

   PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.is earlier. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.

Secondary Outcome Measures

1. Progression Free Survival Rate (PFSR) by Tumor Histology [12 Months after Randomization]

   PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.is earlier. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.

2. Progression Free Survival Rate (PFSR) by Response Criteria [12 Months after Randomization]

   PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.is earlier. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.

3. Overall Survival [Up to 12 Months]

   defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.

4. Overall Survival by Histology [12 Months after Randomization]

   defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.

5. Overall Survival by Response Criteria [12 Months after Randomization]

   defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.

6. Percentage of Participants With an Adverse Events (AEs) [between first dose and 100 days after last dose of study therapy]

   Percentage of Participants with an Adverse Event due to any cause

7. Percentage of Participants With an Serious Adverse Events (SAEs) [between first dose and 100 days after last dose of study therapy]

   Percentage of Participants with an Serious Adverse Event due to any cause

8. Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC) [between first dose and 100 days after last dose of study therapy]

   Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause

9. Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) [between first dose and 100 days after last dose of study therapy]

   Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication

10. Percentage of Participants With an Select Adverse Events [between first dose and 100 days after last dose of study therapy]

    Percentage of Participants with an Select Adverse Event due to any cause

11. Percentage of Participants With an Event of Special Interest (ESI) [between first dose and 100 days after last dose of study therapy]

    Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).

12. Percentage of Participants Who Experienced Death [between first dose and 100 days after last dose of study therapy]

    Percentage of Participants who experienced Death due to any cause

13. Number of Participants With Laboratory Test Abnormalities [between first dose and 100 days after last dose of study therapy]

    number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)

14. Percentage of Participants With an Adverse Event Leading to Dose Delays (AEsDD) [between first dose and 100 days after last dose of study therapy]

    Percentage of Participants with an Adverse Event leading to a Dose Delay due to any cause

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histologically or cytologically documented Squamous or non-Squamous Non-small cell lung cancer (NSCLC) (Stage IIIB/IV), or recurrent or progressive disease following multimodal therapy

• Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD)

• Measurable disease before start of pre-study nivolumab treatment

• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2

Exclusion Criteria:

• Carcinomatous meningitis

• Untreated, symptomatic Central nervous system (CNS) metastases

• Symptomatic interstitial lung disease

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Oncology	Birmingham	Alabama	United States	35205
2	Arizona Oncology Assoc, Pc-Hal	Phoenix	Arizona	United States	85016
3	Arizona Oncology Associates PC - NAHOA	Phoenix	Arizona	United States	85016
4	CBCC Global Research, Inc.	Bakersfield	California	United States	93309
5	Southern California Permanente Medical Group	Bellflower	California	United States	90706
6	St Jude Hospital Yorba Linda	Fullerton	California	United States	92835
7	UCLA Hematology/Oncology Clinic	Los Angeles	California	United States	90095
8	Torrance Health Association	Redondo Beach	California	United States	90227
9	Sharp Memorial Hospital	San Diego	California	United States	92123
10	Sansum Clinic	Santa Barbara	California	United States	93015
11	Central Coast Med Oncology	Santa Maria	California	United States	93454
12	Kaiser Permanente Medical Center (clinic+DSL)	Vallejo	California	United States	94589
13	Rocky Mountain Cancer Centers Llp	Denver	Colorado	United States	80218-1210
14	Poudre Valley Health Care	Fort Collins	Colorado	United States	80528
15	Florida Cancer Specialists S.	Fort Myers	Florida	United States	33901
16	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
17	Ocala Oncology Center, Pl	Ocala	Florida	United States	34471
18	Sacred Heart Medical Oncology Group	Pensacola	Florida	United States	32504
19	Florida Cancer Specialists	Saint Petersburg	Florida	United States	33705
20	University Cancer Blood Ctr	Athens	Georgia	United States	30607
21	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
22	Northwest Georgia Oncology Ctr	Marietta	Georgia	United States	30060
23	Ingalls Health System	Harvey	Illinois	United States	60426
24	Illinois Cancer Specialists	Niles	Illinois	United States	60714
25	Illinois Cancercare, PC	Peoria	Illinois	United States	61615
26	Ft. Wayne Med Onco-Hema Inc	Fort Wayne	Indiana	United States	46804
27	Innova Schar Cancer Institute	Indianapolis	Indiana	United States	46237
28	Cancer Center Of Kansas	Wichita	Kansas	United States	67214
29	Oncology Associated Of Western Kentucky	Paducah	Kentucky	United States	42003
30	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
31	Cancer Care Of Maine	Brewer	Maine	United States	04412
32	Center For Cancer And Blood Disorders	Bethesda	Maryland	United States	20817
33	Providence Cancer Center	Southfield	Michigan	United States	48075
34	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
35	North Mississippi Med Center	Tupelo	Mississippi	United States	38801
36	Mercy Medical Research Institute	Springfield	Missouri	United States	65806
37	Oncology Hematology West PC	Omaha	Nebraska	United States	68130
38	New York Oncology Hematology, P.C.	Albany	New York	United States	12206
39	Broome Oncology	Johnson City	New York	United States	13790
40	First Health Of The Carolinas	Pinehurst	North Carolina	United States	28374
41	Hematology And Oncology Associates	Canton	Ohio	United States	44708
42	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45242
43	MetroHealth Cancer Care Center	Cleveland	Ohio	United States	44109
44	Tri-County Hematology & Oncology Associates, Inc	Massillon	Ohio	United States	44646
45	Hematology Oncology Consultants, Pc	Medford	Oregon	United States	97504
46	Charleston Hematology Oncology Associates, Pa	Charleston	South Carolina	United States	29414
47	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
48	Jones Clinic PC	Germantown	Tennessee	United States	38138
49	Tennessee Oncology, PLLC - SCRI - PPDS	Nashville	Tennessee	United States	37203
50	Texas Oncology, P.A.	Abilene	Texas	United States	79606-5208
51	Texas Oncology - Amarillo	Amarillo	Texas	United States	79106
52	Texas Oncology, P.A.	Dallas	Texas	United States	75230
53	Texas Oncology, P.A.	Dallas	Texas	United States	75231
54	Texas Oncology, P.A.	Denton	Texas	United States	76210
55	Texas Oncology, P.A.	El Paso	Texas	United States	79902
56	Texas Oncology, P.A.	Flower Mound	Texas	United States	75028
57	Texas Oncology, P.A.	Houston	Texas	United States	77024
58	Texas Oncology, P.A.	Longview	Texas	United States	75601
59	Texas Oncology-Midland Allison Cancer Center	Midland	Texas	United States	79701
60	Texas Oncology, P.A.	Plano	Texas	United States	75093
61	Texas Oncology, P.A.	San Antonio	Texas	United States	78212
62	Texas Oncology, P.A.	Sherman	Texas	United States	75090
63	Texas Oncology, P.A.	Sugar Land	Texas	United States	77479
64	Texas Oncology	Wichita Falls	Texas	United States	76310
65	Innova Schar Cancer Institute	Falls Church	Virginia	United States	22042
66	Shenandoah Oncology	Winchester	Virginia	United States	22601
67	Cancer Care Northwest	Spokane Valley	Washington	United States	99216
68	Northwest Cancer Specialists, P.C.	Vancouver	Washington	United States	98684
69	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington	United States	98902
70	Local Institution	St. Leonards	New South Wales	Australia	2065
71	Local Institution	Waratah	New South Wales	Australia	2298
72	Local Institution	Westmead,	New South Wales	Australia	2145
73	Local Institution	Woolloongabba	Queensland	Australia	4102
74	Local Institution	Bedford Park	South Australia	Australia	5042
75	Local Institution	Elizabeth Vale	South Australia	Australia	5112
76	Local Institution	Kurralta Park	South Australia	Australia	5037
77	Local Institution	Hobart	Tasmania	Australia	7000
78	Local Institution	Heidelberg	Victoria	Australia	3084
79	Local Institution	Murdoch	Western Australia	Australia	6150
80	Local Institution	Wien		Austria	1090
81	Local Institution	Newmarket	Ontario	Canada	L3Y 2P9
82	Local Institution	Montreal	Quebec	Canada	H4J 1C5
83	Local Institution	St. Jerome	Quebec	Canada	J7Z 5T3
84	Local Institution	Quebec		Canada	GIJ 1Z4
85	Local Institution	Angers		France	49000
86	Local Institution	Bayonne		France	64109
87	Local Institution	Clermont-Ferrand Cedex 01		France	63003
88	Local Institution	Le Mans		France	72000
89	Local Institution	Mulhouse		France	68100
90	Local Institution	Nimes		France	30029
91	Local Institution	Paris		France	75005
92	Local Institution	Paris		France	75014
93	Local Institution	Pontoise		France	95300
94	Local Institution	Suresnes Cedex		France	92 151
95	Local Institution	Tours		France	37044
96	Local Institution	Vandoeuvre-les-Nancy		France	54519
97	Local Institution	Villefranche-sur-Saone Cedex		France	69655
98	Local Institution	Bad Berka		Germany	99437
99	Local Institution	Berlin		Germany	13353
100	Local Institution	Dresden		Germany	01307
101	Local Institution	Freiburg		Germany	79106
102	Local Institution	Gauting		Germany	82131
103	Local Institution	Greifenstein		Germany	35753
104	Local Institution	Hamburg		Germany	20251
105	Local Institution	Hannover		Germany	30625
106	Local Institution	Kassel		Germany	34125
107	Local Institution	Kiel		Germany	24105
108	Local Institution	Leipzig		Germany	04357
109	Local Institution	Lostau		Germany	39291
110	Local Institution	Moers		Germany	47447
111	Local Institution	Nürnberg		Germany	90419
112	Local Institution	Localita San Filippo Lucca		Italy	55100
113	Local Institution	Monza		Italy	20900
114	Local Institution	Napoli		Italy	80131
115	Local Institution	Roma		Italy	00128
116	Local Institution	Barcelona		Spain	08208
117	Local Institution	El Palmar		Spain	30120
118	Local Institution	Las Palmas de Gran Canaria		Spain	35016
119	Local Institution	Sevilla		Spain	41013

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Nov 3, 2015
• Statistical Analysis Plan - Sep 28, 2018

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02713867
• Other Study ID Numbers: CA209-384
• First Posted: Mar 21, 2016
• Last Update Posted: Mar 22, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Nivolumab

Study Results

Participant Flow

Pre-assignment Detail	363 Enrolled (Randomized), 358 Treated; reasons not treated: 3 Other Reasons, 2 withdrew consent.

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Period Title: Randomization
STARTED	180	183
COMPLETED	178	180
NOT COMPLETED	2	3
Period Title: Randomization
STARTED	178	180
COMPLETED	31	30
NOT COMPLETED	147	150

Baseline Characteristics

Arm/Group Title	Treatment A	Treatment B	Total
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W	Total of all reporting groups
Overall Participants	180	183	363
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.4 (9.25)	66.5 (8.65)	66.5 (8.94)
Sex: Female, Male (Count of Participants)
Female	49 27.2%	54 29.5%	103 28.4%
Male	131 72.8%	129 70.5%	260 71.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 1.7%	4 2.2%	7 1.9%
Not Hispanic or Latino	118 65.6%	115 62.8%	233 64.2%
Unknown or Not Reported	59 32.8%	64 35%	123 33.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.6%	3 1.6%	4 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 4.4%	8 4.4%	16 4.4%
White	169 93.9%	167 91.3%	336 92.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.1%	5 2.7%	7 1.9%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival Rate(PFSR) at 6 Months
Description	PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.
Time Frame	at 6 Months

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
Number (95% Confidence Interval) [Probability]	0.76	0.79

2. Primary Outcome

Title	Progression Free Survival Rate (PFSR) at 12 Months
Description	PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.is earlier. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.
Time Frame	at 12 Months

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
Number (95% Confidence Interval) [Probability]	0.53	0.55

3. Secondary Outcome

Title	Progression Free Survival Rate (PFSR) by Tumor Histology
Description	PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.is earlier. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.
Time Frame	12 Months after Randomization

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
Squamous	0.50	0.42
Non Squamous	0.54	0.60

4. Secondary Outcome

Title	Progression Free Survival Rate (PFSR) by Response Criteria
Description	PFS is defined as the time from the date of randomization to the date of first documented tumor progression determined by the investigator or death, whichever is earlier. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment.is earlier. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.
Time Frame	12 Months after Randomization

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
Complete Remission (CR)/Partial Remission (PR)	0.63	0.66
Stable Disease (SD)	0.47	0.48

5. Secondary Outcome

Title	Overall Survival
Description	defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Time Frame	Up to 12 Months

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
At 12 Months	0.851	0.908
At 6 Months	0.966	0.956

6. Secondary Outcome

Title	Overall Survival by Histology
Description	defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Time Frame	12 Months after Randomization

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
Squamous	0.74	0.80
Non Squamous	0.86	0.92

7. Secondary Outcome

Title	Overall Survival by Response Criteria
Description	defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Time Frame	12 Months after Randomization

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	180	183
CR/PR	0.90	0.93
SD	0.78	0.85

8. Secondary Outcome

Title	Percentage of Participants With an Adverse Events (AEs)
Description	Percentage of Participants with an Adverse Event due to any cause
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Number [Percentage of Participants]	90.4 50.2%	97.8 53.4%

9. Secondary Outcome

Title	Percentage of Participants With an Serious Adverse Events (SAEs)
Description	Percentage of Participants with an Serious Adverse Event due to any cause
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Number [Percentage of Participants]	32.0 17.8%	38.3 20.9%

10. Secondary Outcome

Title	Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC)
Description	Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Number [Percentage of Participants]	16.9 9.4%	17.2 9.4%

11. Secondary Outcome

Title	Percentage of Participants With an Immune Mediated Adverse Events (IMAEs)
Description	Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Diarrhea/Colitis	3.4 1.9%	6.1 3.3%
Hepatitis	0.0 0%	1.1 0.6%
Pneumonitis	1.7 0.9%	3.3 1.8%
Nephritis and Renal Dysfunction	0.6 0.3%	0.0 0%
Rash	7.3 4.1%	6.7 3.7%
Hypersensitivity/Infusion Reaction	0.0 0%	0.0 0%

12. Secondary Outcome

Title	Percentage of Participants With an Select Adverse Events
Description	Percentage of Participants with an Select Adverse Event due to any cause
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Gastrointestinal	17.4 9.7%	24.4 13.3%
Hepatic	1.7 0.9%	10.0 5.5%
Pulmonary	6.2 3.4%	5.0 2.7%
Renal	10.1 5.6%	5.6 3.1%
Skin	28.7 15.9%	32.2 17.6%
Hypersensitivity/Infusion Reaction	0.0 0%	1.1 0.6%
Endocrine	16.3 9.1%	18.9 10.3%

13. Secondary Outcome

Title	Percentage of Participants With an Event of Special Interest (ESI)
Description	Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Pancreatitis	1.1 0.6%	2.8 1.5%
demyelination	0 0%	0 0%
encephalitis	0 0%	0 0%
GBS	0 0%	0 0%
myasthenic syndrome	0 0%	0 0%
uveitis	0 0%	0 0%
myositis	0 0%	0 0%
myocarditis	0 0%	0 0%
rhabdomyolysis	0 0%	0 0%
GVHD	0 0%	0 0%

14. Secondary Outcome

Title	Percentage of Participants Who Experienced Death
Description	Percentage of Participants who experienced Death due to any cause
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Number [Percentage of Participants]	36.0 20%	28.3 15.5%

15. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities
Description	number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Alanine Aminotransferase	1 0.6%	1 0.5%
Alkaline Phosphate	1 0.6%	0 0%
Aspartate Aminotransferase	1 0.6%	2 1.1%
Bilirubin, Total	1 0.6%	1 0.5%
Creatinine	1 0.6%	2 1.1%
Hemoglobin	0 0%	4 2.2%
Hypercalcemia	2 1.1%	5 2.7%
Hyperkalemia	4 2.2%	3 1.6%
Hypermagnesemia	4 2.2%	5 2.7%
Hypernatremia	0 0%	0 0%
Hypocalcemia	4 2.2%	6 3.3%
Hypokalemia	3 1.7%	6 3.3%
Hypomagnesemia	3 1.7%	2 1.1%
Hypnatremia	6 3.3%	7 3.8%
Leukocytes	1 0.6%	3 1.6%
Lymphocytes	22 12.2%	21 11.5%
Neutrophils	3 1.7%	4 2.2%
Platelet Count	3 1.7%	1 0.5%

16. Secondary Outcome

Title	Percentage of Participants With an Adverse Event Leading to Dose Delays (AEsDD)
Description	Percentage of Participants with an Adverse Event leading to a Dose Delay due to any cause
Time Frame	between first dose and 100 days after last dose of study therapy

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab 480mg Q4W	Nivolumab 240mg Q2W
Measure Participants	178	180
Number [Percentage of Participants]	NA NaN	NA NaN

Adverse Events

Time Frame	between first dose and 100 days after last dose, (up to 4 years)
Arm/Group Title	Treatment A		Treatment B
Arm/Group Description	Nivolumab 480mg Q4W		Nivolumab 240mg Q2W
All Cause Mortality
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/178 (36%)		51/180 (28.3%)
Serious Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/178 (32%)		69/180 (38.3%)
Cardiac disorders
Acute myocardial infarction	1/178 (0.6%)		0/180 (0%)
Cardiac failure	1/178 (0.6%)		0/180 (0%)
Coronary artery occlusion	1/178 (0.6%)		0/180 (0%)
Myocardial infarction	0/178 (0%)		1/180 (0.6%)
Supraventricular tachycardia	0/178 (0%)		1/180 (0.6%)
Congenital, familial and genetic disorders
Phimosis	1/178 (0.6%)		0/180 (0%)
Endocrine disorders
Adrenal insufficiency	1/178 (0.6%)		0/180 (0%)
Hypophysitis	1/178 (0.6%)		0/180 (0%)
Inappropriate antidiuretic hormone secretion	0/178 (0%)		1/180 (0.6%)
Gastrointestinal disorders
Abdominal pain upper	0/178 (0%)		1/180 (0.6%)
Autoimmune colitis	0/178 (0%)		1/180 (0.6%)
Colitis	0/178 (0%)		1/180 (0.6%)
Colitis ulcerative	0/178 (0%)		1/180 (0.6%)
Diarrhoea	4/178 (2.2%)		1/180 (0.6%)
Gastrointestinal haemorrhage	1/178 (0.6%)		0/180 (0%)
Gastrointestinal pain	1/178 (0.6%)		0/180 (0%)
Ileus	0/178 (0%)		1/180 (0.6%)
Nausea	1/178 (0.6%)		0/180 (0%)
Pancreatitis	1/178 (0.6%)		0/180 (0%)
Pancreatitis acute	0/178 (0%)		1/180 (0.6%)
Rectal haemorrhage	1/178 (0.6%)		0/180 (0%)
Small intestinal obstruction	1/178 (0.6%)		0/180 (0%)
Stomatitis	0/178 (0%)		1/180 (0.6%)
Upper gastrointestinal haemorrhage	0/178 (0%)		1/180 (0.6%)
Vomiting	2/178 (1.1%)		0/180 (0%)
General disorders
Asthenia	0/178 (0%)		1/180 (0.6%)
Drowning	1/178 (0.6%)		0/180 (0%)
Fatigue	1/178 (0.6%)		0/180 (0%)
Multiple organ dysfunction syndrome	0/178 (0%)		1/180 (0.6%)
Sudden death	1/178 (0.6%)		0/180 (0%)
Systemic inflammatory response syndrome	1/178 (0.6%)		0/180 (0%)
Hepatobiliary disorders
Cholecystitis	1/178 (0.6%)		0/180 (0%)
Hepatitis	0/178 (0%)		1/180 (0.6%)
Infections and infestations
Bronchitis	1/178 (0.6%)		0/180 (0%)
Clostridium difficile colitis	0/178 (0%)		1/180 (0.6%)
Cystitis	1/178 (0.6%)		0/180 (0%)
Erysipelas	1/178 (0.6%)		1/180 (0.6%)
Herpes zoster	0/178 (0%)		1/180 (0.6%)
Infective exacerbation of chronic obstructive airways disease	2/178 (1.1%)		0/180 (0%)
Influenza	1/178 (0.6%)		0/180 (0%)
Lower respiratory tract infection	0/178 (0%)		2/180 (1.1%)
Lung abscess	0/178 (0%)		1/180 (0.6%)
Lung infection	0/178 (0%)		1/180 (0.6%)
Medical device site cellulitis	1/178 (0.6%)		0/180 (0%)
Neutropenic sepsis	0/178 (0%)		1/180 (0.6%)
Pneumonia	5/178 (2.8%)		8/180 (4.4%)
Pneumonia bacterial	0/178 (0%)		1/180 (0.6%)
Postoperative wound infection	1/178 (0.6%)		0/180 (0%)
Pulmonary sepsis	1/178 (0.6%)		0/180 (0%)
Respiratory tract infection	0/178 (0%)		1/180 (0.6%)
Sepsis	3/178 (1.7%)		1/180 (0.6%)
Upper respiratory tract infection	1/178 (0.6%)		0/180 (0%)
Upper respiratory tract infection bacterial	1/178 (0.6%)		0/180 (0%)
Urinary tract infection	1/178 (0.6%)		1/180 (0.6%)
Urosepsis	1/178 (0.6%)		0/180 (0%)
Injury, poisoning and procedural complications
Animal bite	0/178 (0%)		1/180 (0.6%)
Fall	1/178 (0.6%)		1/180 (0.6%)
Femoral neck fracture	1/178 (0.6%)		0/180 (0%)
Femur fracture	1/178 (0.6%)		1/180 (0.6%)
Humerus fracture	0/178 (0%)		1/180 (0.6%)
Perirenal haematoma	0/178 (0%)		1/180 (0.6%)
Post procedural haematuria	0/178 (0%)		1/180 (0.6%)
Procedural pain	1/178 (0.6%)		0/180 (0%)
Road traffic accident	1/178 (0.6%)		0/180 (0%)
Spinal compression fracture	0/178 (0%)		2/180 (1.1%)
Wound evisceration	0/178 (0%)		1/180 (0.6%)
Investigations
Alanine aminotransferase increased	0/178 (0%)		1/180 (0.6%)
Aspartate aminotransferase increased	0/178 (0%)		1/180 (0.6%)
Metabolism and nutrition disorders
Dehydration	2/178 (1.1%)		0/180 (0%)
Diabetes mellitus	1/178 (0.6%)		1/180 (0.6%)
Failure to thrive	1/178 (0.6%)		0/180 (0%)
Hyperkalaemia	1/178 (0.6%)		0/180 (0%)
Hypokalaemia	1/178 (0.6%)		0/180 (0%)
Hyponatraemia	0/178 (0%)		1/180 (0.6%)
Musculoskeletal and connective tissue disorders
Arthritis	0/178 (0%)		1/180 (0.6%)
Back pain	1/178 (0.6%)		1/180 (0.6%)
Lumbar spinal stenosis	0/178 (0%)		1/180 (0.6%)
Musculoskeletal chest pain	1/178 (0.6%)		0/180 (0%)
Musculoskeletal pain	0/178 (0%)		1/180 (0.6%)
Osteoarthritis	1/178 (0.6%)		0/180 (0%)
Osteoporosis	0/178 (0%)		1/180 (0.6%)
Polymyalgia rheumatica	0/178 (0%)		1/180 (0.6%)
Soft tissue disorder	0/178 (0%)		1/180 (0.6%)
Spinal pain	0/178 (0%)		1/180 (0.6%)
Spondylolisthesis	0/178 (0%)		1/180 (0.6%)
Thoracic spinal stenosis	0/178 (0%)		1/180 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glottis carcinoma	0/178 (0%)		1/180 (0.6%)
Laryngeal cancer	0/178 (0%)		1/180 (0.6%)
Lung neoplasm malignant	1/178 (0.6%)		0/180 (0%)
Malignant melanoma	1/178 (0.6%)		0/180 (0%)
Malignant neoplasm progression	2/178 (1.1%)		9/180 (5%)
Metastases to central nervous system	0/178 (0%)		1/180 (0.6%)
Prostate cancer	0/178 (0%)		1/180 (0.6%)
Rectal adenocarcinoma	1/178 (0.6%)		0/180 (0%)
Squamous cell carcinoma of skin	0/178 (0%)		1/180 (0.6%)
Nervous system disorders
Cerebral ischaemia	0/178 (0%)		1/180 (0.6%)
Cerebrovascular accident	1/178 (0.6%)		0/180 (0%)
Encephalopathy	0/178 (0%)		1/180 (0.6%)
Nystagmus	0/178 (0%)		1/180 (0.6%)
Seizure	0/178 (0%)		2/180 (1.1%)
Syncope	1/178 (0.6%)		1/180 (0.6%)
Psychiatric disorders
Confusional state	0/178 (0%)		1/180 (0.6%)
Depression	1/178 (0.6%)		0/180 (0%)
Renal and urinary disorders
Renal failure	0/178 (0%)		1/180 (0.6%)
Urinary retention	1/178 (0.6%)		0/180 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/178 (0.6%)		0/180 (0%)
Prostatitis	1/178 (0.6%)		0/180 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/178 (0%)		2/180 (1.1%)
Chronic obstructive pulmonary disease	5/178 (2.8%)		3/180 (1.7%)
Dyspnoea	1/178 (0.6%)		1/180 (0.6%)
Haemoptysis	1/178 (0.6%)		0/180 (0%)
Pneumonitis	3/178 (1.7%)		5/180 (2.8%)
Pneumothorax	1/178 (0.6%)		1/180 (0.6%)
Pulmonary embolism	0/178 (0%)		4/180 (2.2%)
Pulmonary hypertension	1/178 (0.6%)		0/180 (0%)
Respiratory failure	1/178 (0.6%)		0/180 (0%)
Vascular disorders
Aortic aneurysm	1/178 (0.6%)		0/180 (0%)
Hypotension	0/178 (0%)		1/180 (0.6%)
Infarction	1/178 (0.6%)		0/180 (0%)
Peripheral artery occlusion	0/178 (0%)		1/180 (0.6%)
Peripheral ischaemia	1/178 (0.6%)		0/180 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	138/178 (77.5%)		167/180 (92.8%)
Blood and lymphatic system disorders
Anaemia	10/178 (5.6%)		19/180 (10.6%)
Endocrine disorders
Hypothyroidism	21/178 (11.8%)		16/180 (8.9%)
Gastrointestinal disorders
Abdominal pain	10/178 (5.6%)		7/180 (3.9%)
Abdominal pain upper	5/178 (2.8%)		10/180 (5.6%)
Constipation	19/178 (10.7%)		22/180 (12.2%)
Diarrhoea	28/178 (15.7%)		40/180 (22.2%)
Gastrooesophageal reflux disease	7/178 (3.9%)		11/180 (6.1%)
Nausea	12/178 (6.7%)		28/180 (15.6%)
Vomiting	12/178 (6.7%)		18/180 (10%)
General disorders
Asthenia	23/178 (12.9%)		22/180 (12.2%)
Fatigue	29/178 (16.3%)		40/180 (22.2%)
Non-cardiac chest pain	6/178 (3.4%)		10/180 (5.6%)
Oedema peripheral	11/178 (6.2%)		15/180 (8.3%)
Pyrexia	14/178 (7.9%)		14/180 (7.8%)
Infections and infestations
Bronchitis	16/178 (9%)		22/180 (12.2%)
Nasopharyngitis	11/178 (6.2%)		16/180 (8.9%)
Rhinitis	1/178 (0.6%)		10/180 (5.6%)
Sinusitis	7/178 (3.9%)		10/180 (5.6%)
Upper respiratory tract infection	8/178 (4.5%)		14/180 (7.8%)
Urinary tract infection	4/178 (2.2%)		10/180 (5.6%)
Injury, poisoning and procedural complications
Fall	8/178 (4.5%)		11/180 (6.1%)
Investigations
Blood creatinine increased	14/178 (7.9%)		7/180 (3.9%)
Lipase increased	8/178 (4.5%)		14/180 (7.8%)
Weight decreased	8/178 (4.5%)		18/180 (10%)
Metabolism and nutrition disorders
Decreased appetite	14/178 (7.9%)		20/180 (11.1%)
Hyperkalaemia	4/178 (2.2%)		13/180 (7.2%)
Hypomagnesaemia	3/178 (1.7%)		10/180 (5.6%)
Hypophosphataemia	3/178 (1.7%)		11/180 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/178 (9%)		27/180 (15%)
Back pain	24/178 (13.5%)		18/180 (10%)
Muscle spasms	3/178 (1.7%)		11/180 (6.1%)
Musculoskeletal pain	8/178 (4.5%)		16/180 (8.9%)
Myalgia	3/178 (1.7%)		11/180 (6.1%)
Pain in extremity	9/178 (5.1%)		15/180 (8.3%)
Nervous system disorders
Dizziness	4/178 (2.2%)		17/180 (9.4%)
Headache	13/178 (7.3%)		14/180 (7.8%)
Psychiatric disorders
Insomnia	5/178 (2.8%)		20/180 (11.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	8/178 (4.5%)		10/180 (5.6%)
Cough	24/178 (13.5%)		40/180 (22.2%)
Dyspnoea	22/178 (12.4%)		25/180 (13.9%)
Skin and subcutaneous tissue disorders
Dry skin	6/178 (3.4%)		11/180 (6.1%)
Pruritus	20/178 (11.2%)		31/180 (17.2%)
Pruritus generalised	14/178 (7.9%)		12/180 (6.7%)
Rash	8/178 (4.5%)		10/180 (5.6%)
Rash maculo-papular	9/178 (5.1%)		6/180 (3.3%)
Vascular disorders
Hypertension	10/178 (5.6%)		11/180 (6.1%)

Limitations/Caveats

No formal statistical analyses were conducted. Median OS was not reached in either arm.

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.