History of Changes for Study: NCT02041533

An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)

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Study Record Versions

Version	Submitted Date	Changes
1	January 19, 2014	None (earliest Version on record)
2	February 28, 2014	Study Status
3	March 26, 2014	Recruitment Status, Study Status and Contacts/Locations
4	April 29, 2014	Contacts/Locations, Study Status and References
5	May 7, 2014	Contacts/Locations and Study Status
6	May 27, 2014	Contacts/Locations and Study Status
7	May 30, 2014	Study Status
8	July 4, 2014	Contacts/Locations and Study Status
9	July 9, 2014	Contacts/Locations and Study Status
10	July 23, 2014	Contacts/Locations and Study Status
11	August 11, 2014	Contacts/Locations and Study Status
12	August 28, 2014	Contacts/Locations and Study Status
13	September 15, 2014	Contacts/Locations and Study Status
14	September 22, 2014	Contacts/Locations and Study Status
15	October 13, 2014	Contacts/Locations and Study Status
16	October 30, 2014	Contacts/Locations and Study Status
17	November 13, 2014	Contacts/Locations and Study Status
18	November 20, 2014	Contacts/Locations and Study Status
19	December 5, 2014	Contacts/Locations and Study Status
20	December 31, 2014	Contacts/Locations and Study Status
21	January 27, 2015	Contacts/Locations and Study Status
22	February 26, 2015	Contacts/Locations, Study Status and Sponsor/Collaborators
23	March 5, 2015	Contacts/Locations and Study Status
24	March 23, 2015	Contacts/Locations and Study Status
25	April 13, 2015	Contacts/Locations and Study Status
26	April 20, 2015	Contacts/Locations and Study Status
27	May 6, 2015	Contacts/Locations, Study Status and Study Design
28	May 20, 2015	Study Status
29	June 3, 2015	Study Status
30	June 22, 2015	Contacts/Locations and Study Status
31	July 3, 2015	Contacts/Locations and Study Status
32	July 17, 2015	Contacts/Locations and Study Status
33	August 4, 2015	Contacts/Locations and Study Status
34	August 18, 2015	Study Status
35	September 3, 2015	Contacts/Locations and Study Status
36	September 16, 2015	Contacts/Locations and Study Status
37	October 5, 2015	Recruitment Status, Contacts/Locations and Study Status
38	October 15, 2015	Study Status
39	November 4, 2015	Contacts/Locations and Study Status
40	November 18, 2015	Study Status
41	December 8, 2015	Study Status and Contacts/Locations
42	December 21, 2015	Study Status
43	January 6, 2016	Study Status
44	January 21, 2016	Study Status
45	January 26, 2016	Study Status
46	February 10, 2016	Study Status
47	February 25, 2016	Study Status
48	March 11, 2016	Study Status
49	March 28, 2016	Study Status
50	April 12, 2016	Study Status
51	April 21, 2016	Study Status
52	April 25, 2016	Study Status
53	May 10, 2016	Study Status
54	May 25, 2016	Study Status
55	June 9, 2016	Study Status
56	June 24, 2016	Study Status
57	July 11, 2016	Study Status
58	July 26, 2016	Study Status
59	August 8, 2016	Study Status
60	August 23, 2016	Study Status
61	September 15, 2016	Study Status
62	September 23, 2016	Study Status
63	October 7, 2016	Study Status
64	October 26, 2016	Study Status
65	November 8, 2016	Study Status
66	November 30, 2016	Study Status
67	December 6, 2016	Study Status
68	December 23, 2016	Study Status
69	January 5, 2017	Study Status
70	January 23, 2017	Contacts/Locations and Study Status
71	January 27, 2017	Study Status
72	February 16, 2017	Study Status
73	March 3, 2017	Study Status
74	March 29, 2017	Study Status
75	April 17, 2017	Contacts/Locations and Study Status
76	June 26, 2017	Study Status, Outcome Measures, Contacts/Locations, References, Study Design, Oversight and Results
77	July 25, 2017	Participant Flow and Study Status
78	January 18, 2018	Contacts/Locations and Study Status
79	August 21, 2019	Contacts/Locations, Study Status, References and Outcome Measures
80	November 15, 2019	Study Status and Contacts/Locations
81	December 10, 2019	Study Status
82	January 24, 2020	Study Status and Contacts/Locations
83	May 14, 2020	Study Status and Contacts/Locations
84	June 16, 2020	Study Status
85	July 6, 2020	Contacts/Locations and Study Status
86	June 9, 2021	Contacts/Locations and Study Status
87	March 8, 2022	Contacts/Locations, Study Status, References, Eligibility and Oversight
88	May 2, 2022	Study Status and Contacts/Locations
89	July 19, 2022	Recruitment Status, Study Status and Contacts/Locations
90	February 2, 2023	Adverse Events, Outcome Measures, Participant Flow, Baseline Characteristics, Contacts/Locations, Study Status, More Information and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	CA209-026
Brief Title:	An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)
Official Title:	An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer
Secondary IDs:	2012-004502-93 [EudraCT Number]

Study Status


Record Verification:	February 2023
Overall Status:	Completed
Study Start:	March 27, 2014
Primary Completion:	July 1, 2016 [Actual]
Study Completion:	May 27, 2022 [Actual]

First Submitted:	January 19, 2014
First Submitted that Met QC Criteria:	January 19, 2014
First Posted:	January 22, 2014 [Estimate]

Results First Submitted:	June 26, 2017
Results First Submitted that Met QC Criteria:	June 26, 2017
Results First Posted:	July 26, 2017 [Actual]

Last Update Submitted that Met QC Criteria:	February 2, 2023
Last Update Posted:	March 2, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	Bristol-Myers Squibb
Responsible Party:	Sponsor
Collaborators:	Ono Pharmaceutical Co. Ltd

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


Brief Summary:	The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy
Detailed Description:

Conditions


Conditions:	Stage IV or Recurrent Non-Small Cell Lung Cancer
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	541 [Actual]

Arms and Interventions

Arms

Assigned Interventions

Experimental: Arm A: Nivolumab subjects

Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure

Biological: Nivolumab

Other Names:

BMS-936558
MDX-1106

Active Comparator: Arm B: Investigator's Choice Chemotherapy

Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first

Squamous subjects:

Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle

Non-Squamous subjects:

Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle

Optional crossover:

Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure

Biological: Nivolumab

Other Names:

BMS-936558
MDX-1106

Drug: Gemcitabine

Other Names:

Gemzar

Drug: Cisplatin

Other Names:

Platinol

Drug: Carboplatin

Other Names:

Paraplatin

Drug: Paclitaxel

Other Names:

Taxol

Drug: Pemetrexed

Other Names:

Alimta

Outcome Measures

[See Results Section.]


Primary Outcome Measures:
1.	Progression-Free Survival in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months) ] Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
Secondary Outcome Measures:
1.	Progression-Free Survival in All Randomized Participants [ Time Frame: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months) ] Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
2.	Overall Survival in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization to date of death (up to approximately 89 months) ] Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.
3.	Overall Survival in All Randomized Participants [ Time Frame: From date of randomization to date of death (up to approximately 89 months) ] Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.
4.	Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5% [ Time Frame: From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months) ] ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treatment beyond progression, BOR was determined from response designations recorded up to the time of initial progression. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.
5.	Disease-related Symptom Improvement Rate by Week 12 [ Time Frame: From date of randomization to week 12 ] The Lung Cancer Symptom Score (LCSS) is a validated instrument designed to assess the impact of treatment on disease-related symptoms. It consists of 6 symptom-specific questions related to dyspnea, cough, fatigue, pain, hemoptysis and anorexia plus 3 summary items: symptom distress, interference with activity, and global HRQoL. The degree of impairment was recorded on a 100 mm visual analogue scale with scores from 0 to 100 with zero representing the best score. Disease-related symptom improvement rate by Week 12 is defined as the proportion of all randomized (all PD-L1+) participants who had 10 points or more decrease from baseline in average symptom burden index score at any time between randomization and Week 12.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1 Histologically confirmed Stage IV, or Recurrent NSCLC with no prior systemic anticancer therapy Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria PD-L1+ on immunohistochemistry testing performed by central lab Men and women, ages ≥ 18 years of age Exclusion Criteria: Known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy Known anaplastic lymphoma kinase (ALK) translocations Untreated central nervous system (CNS) metastases Previous malignancies Active, known or suspected autoimmune disease

Contacts/Locations


Study Officials:	Bristol-Myers Squibb Study Director Bristol-Myers Squibb
Locations:	United States, Alabama
	Southern Cancer Center, Inc. Mobile, Alabama, United States, 36608
	United States, Arizona
	Banner MD Anderson Cancer Center Gilbert, Arizona, United States, 85234
	Local Institution - 0034 Tucson, Arizona, United States, 85704
	United States, California
	Local Institution - 0016 Stanford, California, United States, 94305-5826
	United States, Colorado
	University Of Colorado Hosp Aurora, Colorado, United States, 80045
	United States, Connecticut
	Local Institution - 0020 New Haven, Connecticut, United States, 06520
	United States, Florida
	Local Institution - 0030 Miami, Florida, United States, 33176
	Local Institution - 0033 Ocala, Florida, United States, 34471
	H. Lee Moffitt Cancer Center Tampa, Florida, United States, 33612
	United States, Georgia
	Local Institution - 0010 Atlanta, Georgia, United States, 30322
	Northwest Georgia Oncology Center, P.C. Marietta, Georgia, United States, 30060
	United States, Illinois
	Local Institution - 0037 Chicago, Illinois, United States, 60612-3841
	United States, Kentucky
	Local Institution - 0014 Lexington, Kentucky, United States, 40503
	United States, Louisiana
	Crescent City Research Consortium, LLC Marrero, Louisiana, United States, 70072
	United States, Maryland
	Local Institution - 0024 Baltimore, Maryland, United States, 21287
	United States, Massachusetts
	Local Institution - 0036 Boston, Massachusetts, United States, 02114
	Local Institution - 0070 Boston, Massachusetts, United States, 02215
	United States, New York
	Roswell Park Cancer Institute Buffalo, New York, United States, 14263
	Local Institution - 0009 New York, New York, United States, 10016
	Local Institution - 0005 New York, New York, United States, 10065
	United States, North Carolina
	University Of North Carolina At Chapel Hill Chapel Hill, North Carolina, United States, 27599-7305
	Local Institution - 0003 Durham, North Carolina, United States, 27710
	United States, Ohio
	Local Institution - 0012 Cleveland, Ohio, United States, 44106
	Local Institution - 0027 Columbus, Ohio, United States, 43210
	United States, Oregon
	Oregon Health & Science University Portland, Oregon, United States, 97239-3098
	United States, Pennsylvania
	Local Institution - 0007 Allentown, Pennsylvania, United States, 18103
	Local Institution - 0054 Philadelphia, Pennsylvania, United States, 19104
	Local Institution - 0002 Philadelphia, Pennsylvania, United States, 19111
	Local Institution - 0018 Pittsburgh, Pennsylvania, United States, 15232
	United States, South Carolina
	Local Institution - 0011 Charleston, South Carolina, United States, 29425
	Local Institution - 0038 Greenville, South Carolina, United States, 29601
	United States, Tennessee
	Local Institution - 0008 Nashville, Tennessee, United States, 37232-6307
	United States, Texas
	Local Institution - 0006 Dallas, Texas, United States, 75390
	Local Institution - 0023 Houston, Texas, United States, 77030
	Cancer Centers of South Texas San Antonio, Texas, United States, 78212
	United States, Washington
	Local Institution - 0029 Yakima, Washington, United States, 98902
	Argentina
	Local Institution - 0048 Cordoba, Argentina, 5000
	Local Institution - 0050 Cordoba, Argentina, 5000
	Argentina, Buenos Aires
	Local Institution - 0051 Berazategui, Buenos Aires, Argentina, 1880
	Local Institution - 0049 Capital Federal, Buenos Aires, Argentina, 1426
	Local Institution - 0052 Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1181
	Australia, New South Wales
	Local Institution - 0090 Camperdown, New South Wales, Australia, 2050
	Australia, Queensland
	Local Institution - 0091 Brisbane, Queensland, Australia, 4102
	Australia, South Australia
	Local Institution - 0071 Elizabeth Vale, South Australia, Australia, 5112
	Australia, Victoria
	Local Institution - 0072 Fitzroy, Victoria, Australia, 3065
	Local Institution - 0104 Heidelberg, Victoria, Australia, 3084
	Austria
	Local Institution - 0088 Wels, Austria, 4600
	Local Institution - 0087 Wien, Austria, 1090
	Belgium
	Local Institution - 0044 Brussels, Belgium, 1090
	Local Institution - 0055 Edegem, Belgium, 2650
	Local Institution - 0056 Gent, Belgium, 9000
	Local Institution - 0062 Leuven, Belgium, 3000
	Brazil, Rio Grande Do Sul
	Local Institution - 0134 Ijui, Rio Grande Do Sul, Brazil, 98700-000
	Local Institution - 0133 Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
	Brazil, Sao Paulo
	Local Institution - 0135 Barretos, Sao Paulo, Brazil, 14780-070
	Canada, Alberta
	Local Institution - 0086 Calgary, Alberta, Canada, T2N 4N2
	Canada, Ontario
	Local Institution - 0115 Hamilton, Ontario, Canada, L8V 5C2
	Local Institution - 0113 Toronto, Ontario, Canada, M5G 2M9
	Canada, Quebec
	Local Institution - 0110 Montreal, Quebec, Canada, H2X 3E4
	Local Institution - 0109 Rimouski, Quebec, Canada, G5L 5T1
	Czechia
	Local Institution - 0059 Olomouc, Czechia, 779 00
	Local Institution - 0061 Ostrava - Poruba, Czechia, 708 52
	Local Institution - 0058 Praha 8, Czechia, 180 81
	Local Institution - 0060 Usti nad Labem, Czechia, 401 13
	Finland
	Local Institution - 0120 Helsinki, Finland, 00029
	Local Institution - 0119 Tampere, Finland, 33521
	Local Institution - 0118 Vaasa, Finland, 65130
	France
	Local Institution - 0123 Caen, France, 14000
	Local Institution - 0105 Lille, France, 59000
	Local Institution - 0102 Marseille Cedex 20, France, 13915
	Local Institution - 0167 Pontoise Cedex, France, 95303
	Local Institution - 0100 Rennes Cedex 9, France, 35033
	Local Institution - 0140 Strasbourg, France, 67090
	Germany
	Local Institution - 0074 Bamberg, Germany, 96049
	Local Institution - 0065 Grosshansdorf, Germany, 22927
	Local Institution - 0064 Heidelberg, Germany, 69126
	Local Institution - 0063 Koeln, Germany, 50937
	Local Institution - 0066 Stuttgart, Germany, 70376
	Local Institution - 0092 Wiesbaden, Germany, 65199
	Greece
	Local Institution - 0075 Athens, Greece, 11527
	Greece, Creta
	Local Institution - 0073 Heraklion, Creta, Greece, 71110
	Hungary
	Local Institution - 0126 Budapest, Hungary, 1121
	Local Institution - 0116 Debrecen, Hungary, 4032
	Local Institution - 0094 Matrahaza, Hungary, 3233
	Italy
	Local Institution - 0084 Avellino, Italy, 83100
	Local Institution - 0079 Livorno, Italy, 57100
	Local Institution - 0143 Milano, Italy, 20141
	Local Institution - 0142 Napoli, Italy, 80131
	Local Institution - 0083 Perugia, Italy, 06132
	Local Institution - 0082 Terni, Italy, 05100
	Japan
	Local Institution - 0159 Akashi, Hyogo, Japan, 673-8558
	Local Institution - 0162 Ota, Gunma, Japan, 3738550
	Local Institution - 0165 Sapporo, Hokkaido, Japan, 062-0931
	Local Institution - 0160 Tokyo, Japan, 1358550
	Local Institution - 0158 Wakayama, Japan, 641-8510
	Japan, Aichi
	Local Institution - 0146 Nagoya, Aichi, Japan, 4600001
	Local Institution - 0161 Nagoya-shi, Aichi, Japan, 4640021
	Japan, Ehime
	Local Institution - 0148 Matsuyama-shi, Ehime, Japan, 7910280
	Japan, Hyogo
	Local Institution - 0153 Kobe City, Hyogo, Japan, 6500047
	Japan, Miyagi
	Local Institution - 0144 Natori-shi, Miyagi, Japan, 9811293
	Japan, Niigata
	Local Institution - 0151 Niigata-shi, Niigata, Japan, 951-8566
	Japan, Osaka
	Local Institution - 0166 Habikino-shi, Osaka, Japan, 5638588
	Local Institution - 0147 Miyakojima-ku, Osaka, Japan, 534-0021
	Local Institution - 0145 Osaka-sayama, Osaka, Japan, 589-8511
	Local Institution - 0152 Sakai, Osaka, Japan, 591-8555
	Japan, Saitama
	Local Institution - 0150 Kitaadachi-gun, Saitama, Japan, 3620806
	Japan, Shizuoka
	Local Institution - 0149 Sunto-gun, Shizuoka, Japan, 4118777
	Japan, Tokyo
	Local Institution - 0154 Chuo-ku, Tokyo, Japan, 1040045
	Korea, Republic of
	Local Institution - 0155 Gangnam-gu, Korea, Republic of, 06351
	Local Institution - 0164 Seoul, Korea, Republic of, 03722
	Local Institution - 0163 Seoul, Korea, Republic of, 0
	Mexico, Distrito Federal
	Local Institution - 0117 Mexico, Distrito Federal, Mexico, 14080
	Mexico, Jalisco
	Local Institution - 0122 Guadalajara, Jalisco, Mexico, 44280
	Mexico, Yucatan
	Local Institution - 0124 Merida, Yucatan, Mexico, 97133
	Netherlands
	Local Institution - 0045 Amsterdam, Netherlands, 1066 CX
	Local Institution - 0057 Groningen, Netherlands, 9700RB
	Local Institution - 0046 Rotterdam, Netherlands, 3014 GD
	Poland
	Local Institution - 0114 Bydgoszcz, Poland, 85-796
	Local Institution - 0131 Krakow, Poland, 31-202
	Local Institution - 0139 Lodz, Poland, 93-513
	Local Institution - 0089 Warszawa, Poland, 02-781
	Local Institution - 0093 Wodzislaw Slaski, Poland, 44-300
	Romania
	Local Institution - 0068 Cluj Napoca, Romania, 400015
	Local Institution - 0067 Cluj-napoca, Romania, 400352
	Local Institution - 0069 Ploiesti, Romania, 100337
	Spain
	Local Institution - 0040 Barcelona, Spain, 08035
	Local Institution - 0041 Las Palmas De Gran Canaria, Spain, 35016
	Local Institution - 0047 Madrid, Spain, 28050
	Local Institution - 0042 Malaga, Spain, 29010
	Local Institution - 0039 Sevilla, Spain, 41013
	Local Institution - 0043 Valencia, Spain, 46014
	Sweden
	Local Institution - 0127 Stockholm, Sweden, 171 76
	Local Institution - 0125 Uppsala, Sweden, 751 85
	Switzerland
	Local Institution - 0076 Chur, Switzerland, 7000
	Local Institution - 0077 Lausanne, Switzerland, 1011
	Local Institution - 0078 Zuerich, Switzerland, 8091
	Taiwan
	Local Institution - 0157 Taipei, Taiwan, 11217
	Turkey
	Local Institution - 0130 Kayseri, Turkey, 38039
	United Kingdom, Greater London
	Local Institution - 0098 London, Greater London, United Kingdom, N18 1QX
	United Kingdom, Greater Manchester
	Local Institution - 0097 Manchester, Greater Manchester, United Kingdom, M20 4XB
	United Kingdom, Yorkshire
	Local Institution - 0053 Leeds, Yorkshire, United Kingdom, LS9 7TF

IPDSharing


Plan to Share IPD:

References


Links:	URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html Description: BMS Clinical Trial Information
	URL: https://www.bmsstudyconnect.com/s/US/English/USenHome Description: BMS Clinical Trial Patient Recruiting
	URL: https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm Description: FDA Safety Alerts and Recalls
	URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html Description: Investigator Inquiry Form
Available IPD/Information:

Participant Flow

Recruitment Details

Pre-assignment Details

Arm/Group Title

Nivolumab

Investigator Choice of Chemotherapy

Arm/Group Description

Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Administered in 3-week cycles for up to 6 cycles:

Squamous:

gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.

Period Title: Pre-Treatment Period

Started^[1]

271

270

Completed^[2]

267

263

Not Completed

Reason Not Completed

Disease Progression

Participant Withdrew Consent

Participant no Longer Meets Study Criteria

[1]	Started = Participants Randomized
[2]	Completed = Participants Treated

Period Title: Treatment Period

Started

267

263

Received Optional Nivolumab^[1]

159

Completed

Not Completed

267

235

Reason Not Completed

Disease progression

189

146

Study drug toxicity

Death

Adverse event unrelated to study drug

Participant request to discontinue study treatment

Participant withdrew consent

Maximum clinical benefit

Poor/Non-compliance

Administrative reason by sponsor

Other reasons

Not Reported

[1]	Participants in the Investigator Choice Arm who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab.

Baseline Characteristics

Arm/Group Title

Nivolumab

Investigator Choice of Chemotherapy

Total

Arm/Group Description

Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity

Administered in 3-week cycles for up to 6 cycles:

Squamous:

gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or
gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or
paclitaxel (200 mg/m2) with carboplatin (AUC 6)

Non-Squamous:

pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or
pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.

Total of all reporting groups

Overall Number of Baseline Participants

271

270

541

Baseline Analysis Population Description

Age, Continuous

Mean (Standard Deviation)
Unit of measure: years

Number Analyzed

271 Participants

270 Participants

541 Participants

62.8(10.25)

63.4(9.63)

63.1(9.94)

Sex: Female, Male

Measure Type: Count of Participants
Unit of measure: Participants

Number Analyzed

271 Participants

270 Participants

541 Participants

Female

32.1%

122

45.19%

209

38.63%

Male

184

67.9%

148

54.81%

332

61.37%

Ethnicity (NIH/OMB)

Measure Type: Count of Participants
Unit of measure: Participants

Number Analyzed

271 Participants

270 Participants

541 Participants

Hispanic or Latino

1.48%

1.11%

1.29%

Not Hispanic or Latino

141

52.03%

139

51.48%

280

51.76%

Unknown or Not Reported

126

46.49%

128

47.41%

254

46.95%

Race/Ethnicity, Customized^[1]

Measure Type: Number
Unit of measure: Participants

Number Analyzed

271 Participants

270 Participants

541 Participants

White

228

242

470

Black or African American

Asian

American Indian or Alaska Native

Native Hawaiian or Other Pacific Islander

Other

[1]	Measure Description: Race

Outcome Measures

1. Primary Outcome:

Title

Progression-Free Survival in Participants With PD-L1 Expression >= 5%

Description

Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.

Time Frame

From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 expression levels >= 5%


Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
Overall Number of Participants Analyzed	211	212
Median (95% Confidence Interval) Unit of Measure: Months	4.21(2.96 to 5.55)	5.88(5.42 to 6.93)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments	[Not specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not specified]


Statistical Test of Hypothesis	P-Value	0.2511
	Comments	[Not specified]
	Method	Log Rank
	Comments	Log-rank test stratified by histology (squamous vs. non-squamous) as entered into the IVRS.


Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.15
	Confidence Interval	(2-sided) 95% 0.91 to 1.45
	Estimation Comments	Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.

2. Secondary Outcome:

Title

Progression-Free Survival in All Randomized Participants

Description

Time Frame

From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
Overall Number of Participants Analyzed	271	270
Median (95% Confidence Interval) Unit of Measure: Months	4.21(3.06 to 5.52)	5.82(5.42 to 6.90)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments	[Not specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not specified]


Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-sided) 95% 0.95 to 1.43
	Estimation Comments	Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.

3. Secondary Outcome:

Title

Overall Survival in Participants With PD-L1 Expression >= 5%

Description

Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.

Time Frame

From date of randomization to date of death (up to approximately 89 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 expression >= 5%


Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
Overall Number of Participants Analyzed	211	212
Median (95% Confidence Interval) Unit of Measure: Months	14.36(11.66 to 17.08)	13.21(10.81 to 17.28)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments	[Not specified]
	Type of Statistical Test	Superiority
	Comments	[Not specified]


Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-sided) 95% 0.79 to 1.20
	Estimation Comments	Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.

4. Secondary Outcome:

Title

Overall Survival in All Randomized Participants

Description

Time Frame

From date of randomization to date of death (up to approximately 89 months)

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
Overall Number of Participants Analyzed	271	270
Median (95% Confidence Interval) Unit of Measure: Months	13.73(11.76 to 15.41)	13.80(11.01 to 16.99)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments	[Not specified]
	Type of Statistical Test	Superiority
	Comments	[Not specified]


Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-sided) 95% 0.86 to 1.24
	Estimation Comments	Stratified Cox proportional hazard model. Hazard ratio of nivolumab to investigator's choice chemotherapy.

5. Secondary Outcome:

Title

Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5%

Description

ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treatment beyond progression, BOR was determined from response designations recorded up to the time of initial progression. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.

Time Frame

From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 expression >= 5%


Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
Overall Number of Participants Analyzed	211	212
Number (95% Confidence Interval) Unit of Measure: Percentage of participants	26.1(20.3 to 32.5)	33.5(27.2 to 40.3)

Statistical Analysis 1


Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments	[Not specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not specified]


Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.70
	Confidence Interval	(2-sided) 95% 0.46 to 1.06
	Estimation Comments	Stratified by histology (squamous vs.non-squamous) at randomization. Strata adjusted odds ratio (Nivolumab over investigator choice of chemotherapy) using Mantel-Haenszel method.

6. Secondary Outcome:

Title

Disease-related Symptom Improvement Rate by Week 12

Description

The Lung Cancer Symptom Score (LCSS) is a validated instrument designed to assess the impact of treatment on disease-related symptoms. It consists of 6 symptom-specific questions related to dyspnea, cough, fatigue, pain, hemoptysis and anorexia plus 3 summary items: symptom distress, interference with activity, and global HRQoL. The degree of impairment was recorded on a 100 mm visual analogue scale with scores from 0 to 100 with zero representing the best score. Disease-related symptom improvement rate by Week 12 is defined as the proportion of all randomized (all PD-L1+) participants who had 10 points or more decrease from baseline in average symptom burden index score at any time between randomization and Week 12.

Time Frame

From date of randomization to week 12

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
Overall Number of Participants Analyzed	271	270
Number (95% Confidence Interval) Unit of Measure: Percentage of participants	35.4(29.7 to 41.4)	33.7(28.1 to 39.7)

Adverse Events


Time Frame	Participants were assessed for All-Cause Mortality from the date of their randomization until study completion (up to approximately 89 months). SAEs and Other AEs were assessed from their first dose to 100 days following their last dose (up to approximately 89 months).
Adverse Event Reporting Description	The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Arm/Group Title	Nivolumab	Investigator Choice of Chemotherapy	Post Chemotherapy Optional Nivolumab
Arm/Group Description	Nivolumab 3mg/kg IV infusion, every 2 weeks until disease progression or unacceptable toxicity	Administered in 3-week cycles for up to 6 cycles: Squamous: gemcitabine (1250 mg/mg2) with cisplatin (75 mg/m2); or gemcitabine (1000 mg/m2) with carboplatin (AUC 5); or paclitaxel (200 mg/m2) with carboplatin (AUC 6) Non-Squamous: pemetrexed (500 mg/m2) with cisplatin (75 mg/m2); or pemetrexed (500 mg/m2) with carboplatin (AUC 6) Subjects who discontinued cisplatin could be switched to gemcitabine/carboplatin for the remainder of the platinum doublet cycles (up to 6 cycles in total). Participants who progressed on or after chemotherapy could be eligible to receive optional crossover nivolumab 3 mg/kg administered every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.	Participants from the Investigator Choice Arm who progressed during Post-Chemotherapy Phase could receive crossover nivolumab treatment after disease progression. These participants received Nivolumab 3 mg/kg IV infusion every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure.
All-Cause Mortality
	Nivolumab	Investigator Choice of Chemotherapy	Post Chemotherapy Optional Nivolumab
	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)
Total	233 / 271 (85.98%)	92 / 270 (34.07%)	136 / 159 (85.53%)
Serious Adverse Events
	Nivolumab	Investigator Choice of Chemotherapy	Post Chemotherapy Optional Nivolumab
	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)
Total	195 / 267 (73.03%)	203 / 263 (77.19%)	110 / 159 (69.18%)
Blood and lymphatic system disorders
Anaemia ^{† A}	1 / 267 (0.37%)	16 / 263 (6.08%)	2 / 159 (1.26%)
Anaemia of malignant disease ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Febrile neutropenia ^{† A}	3 / 267 (1.12%)	7 / 263 (2.66%)	1 / 159 (0.63%)
Haemolytic anaemia ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Leukopenia ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Neutropenia ^{† A}	0 / 267 (0%)	4 / 263 (1.52%)	1 / 159 (0.63%)
Pancytopenia ^{† A}	1 / 267 (0.37%)	3 / 263 (1.14%)	0 / 159 (0%)
Thrombocytopenia ^{† A}	1 / 267 (0.37%)	6 / 263 (2.28%)	0 / 159 (0%)
Cardiac disorders
Acute coronary syndrome ^{† A}	3 / 267 (1.12%)	1 / 263 (0.38%)	0 / 159 (0%)
Acute left ventricular failure ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Atrial fibrillation ^{† A}	1 / 267 (0.37%)	6 / 263 (2.28%)	3 / 159 (1.89%)
Atrial flutter ^{† A}	0 / 267 (0%)	3 / 263 (1.14%)	2 / 159 (1.26%)
Atrial tachycardia ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Bradycardia ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Cardiac arrest ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Cardiac failure ^{† A}	2 / 267 (0.75%)	4 / 263 (1.52%)	3 / 159 (1.89%)
Cardiac failure acute ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Cardiac failure congestive ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	0 / 159 (0%)
Cardiac tamponade ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Cardiovascular disorder ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Myocardial infarction ^{† A}	0 / 267 (0%)	7 / 263 (2.66%)	4 / 159 (2.52%)
Myocardial ischaemia ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Pericardial effusion ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Pericarditis constrictive ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Sinus bradycardia ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Sinus tachycardia ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Congenital, familial and genetic disorders
Tornwaldt cyst ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Endocrine disorders
Adrenal insufficiency ^{† A}	4 / 267 (1.5%)	4 / 263 (1.52%)	2 / 159 (1.26%)
Hypothyroidism ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Eye disorders
Angle closure glaucoma ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Cataract ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Exophthalmos ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Glaucoma ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Ophthalmic vein thrombosis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Optic nerve disorder ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Gastrointestinal disorders
Abdominal pain ^{† A}	1 / 267 (0.37%)	4 / 263 (1.52%)	1 / 159 (0.63%)
Ascites ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Colitis ^{† A}	4 / 267 (1.5%)	3 / 263 (1.14%)	3 / 159 (1.89%)
Constipation ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	0 / 159 (0%)
Diarrhoea ^{† A}	7 / 267 (2.62%)	6 / 263 (2.28%)	4 / 159 (2.52%)
Dysphagia ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Enteritis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Gastritis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Gastrointestinal haemorrhage ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Ileus ^{† A}	0 / 267 (0%)	3 / 263 (1.14%)	0 / 159 (0%)
Large intestinal obstruction ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Large intestine perforation ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Nausea ^{† A}	4 / 267 (1.5%)	5 / 263 (1.9%)	1 / 159 (0.63%)
Oesophagitis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Small intestinal haemorrhage ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Small intestinal obstruction ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Upper gastrointestinal haemorrhage ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Vomiting ^{† A}	4 / 267 (1.5%)	5 / 263 (1.9%)	1 / 159 (0.63%)
General disorders
Asthenia ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Catheter site pain ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Chest pain ^{† A}	2 / 267 (0.75%)	2 / 263 (0.76%)	0 / 159 (0%)
Death ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Fatigue ^{† A}	2 / 267 (0.75%)	8 / 263 (3.04%)	3 / 159 (1.89%)
General physical health deterioration ^{† A}	4 / 267 (1.5%)	6 / 263 (2.28%)	4 / 159 (2.52%)
Illness ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Localised oedema ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Multiple organ dysfunction syndrome ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Oedema peripheral ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pain ^{† A}	1 / 267 (0.37%)	3 / 263 (1.14%)	1 / 159 (0.63%)
Performance status decreased ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	0 / 159 (0%)
Pyrexia ^{† A}	7 / 267 (2.62%)	9 / 263 (3.42%)	6 / 159 (3.77%)
Sudden death ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Hepatobiliary disorders
Bile duct stenosis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Cholecystitis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Cholecystitis acute ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Cholelithiasis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Cholestasis ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Drug-induced liver injury ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Gallbladder obstruction ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Hepatic failure ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Hepatitis ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Hepatitis acute ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Hypertransaminasaemia ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Jaundice ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Immune system disorders
Hypersensitivity ^{† A}	3 / 267 (1.12%)	0 / 263 (0%)	0 / 159 (0%)
Infections and infestations
Appendicitis ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Appendicitis perforated ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Bronchitis ^{† A}	2 / 267 (0.75%)	3 / 263 (1.14%)	1 / 159 (0.63%)
Cellulitis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Diverticulitis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Erysipelas ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Gastroenteritis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Herpes virus infection ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Infection ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Influenza ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Localised infection ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Lower respiratory tract infection ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Nasopharyngitis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Norovirus infection ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Oral candidiasis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Peritonitis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Pleural infection ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pneumonia ^{† A}	21 / 267 (7.87%)	26 / 263 (9.89%)	8 / 159 (5.03%)
Pneumonia aspiration ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pneumonia bacterial ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Post procedural infection ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Pulmonary sepsis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Respiratory tract infection ^{† A}	1 / 267 (0.37%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Sepsis ^{† A}	5 / 267 (1.87%)	5 / 263 (1.9%)	3 / 159 (1.89%)
Septic shock ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Skin infection ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	0 / 159 (0%)
Subcutaneous abscess ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Upper respiratory tract infection ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Urinary tract infection ^{† A}	3 / 267 (1.12%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Vascular device infection ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Wound infection ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Injury, poisoning and procedural complications
Compression fracture ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Fall ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Femoral neck fracture ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Femur fracture ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	0 / 159 (0%)
Hip fracture ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Infusion related reaction ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Joint dislocation ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Kyphosis postoperative ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Lumbar vertebral fracture ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Procedural pneumothorax ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Radiation necrosis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Radiation pneumonitis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Road traffic accident ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Spinal compression fracture ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Upper limb fracture ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Vascular procedure complication ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Investigations
Alanine aminotransferase increased ^{† A}	5 / 267 (1.87%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Aspartate aminotransferase increased ^{† A}	6 / 267 (2.25%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Blood alkaline phosphatase increased ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Blood bilirubin increased ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Blood creatine phosphokinase increased ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Blood creatinine increased ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	0 / 159 (0%)
C-reactive protein increased ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Gamma-glutamyltransferase increased ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
General physical condition abnormal ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Haemoglobin decreased ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Transaminases increased ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Metabolism and nutrition disorders
Dehydration ^{† A}	4 / 267 (1.5%)	5 / 263 (1.9%)	3 / 159 (1.89%)
Diabetes mellitus ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Hypercalcaemia ^{† A}	3 / 267 (1.12%)	3 / 263 (1.14%)	3 / 159 (1.89%)
Hyperglycaemia ^{† A}	2 / 267 (0.75%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Hypoglycaemia ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Hypokalaemia ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Hyponatraemia ^{† A}	5 / 267 (1.87%)	4 / 263 (1.52%)	2 / 159 (1.26%)
Metabolic acidosis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Musculoskeletal and connective tissue disorders
Arthralgia ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Back pain ^{† A}	2 / 267 (0.75%)	3 / 263 (1.14%)	1 / 159 (0.63%)
Bone pain ^{† A}	1 / 267 (0.37%)	2 / 263 (0.76%)	0 / 159 (0%)
Muscular weakness ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Musculoskeletal chest pain ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Osteolysis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Osteonecrosis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pain in extremity ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Pathological fracture ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Polyarthritis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Spinal stenosis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Cancer pain ^{† A}	8 / 267 (3%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Chronic myeloid leukaemia ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Follicular lymphoma ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Haemangioblastoma ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Intestinal metastasis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Lung cancer metastatic ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Lung neoplasm malignant ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Malignant melanoma ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Malignant neoplasm progression ^{† A}	69 / 267 (25.84%)	95 / 263 (36.12%)	55 / 159 (34.59%)
Malignant pleural effusion ^{† A}	4 / 267 (1.5%)	5 / 263 (1.9%)	3 / 159 (1.89%)
Mesothelioma malignant ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Metastases to bone ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Metastases to central nervous system ^{† A}	2 / 267 (0.75%)	8 / 263 (3.04%)	6 / 159 (3.77%)
Metastases to liver ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Metastases to meninges ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Metastases to spine ^{† A}	3 / 267 (1.12%)	0 / 263 (0%)	0 / 159 (0%)
Neoplasm progression ^{† A}	1 / 267 (0.37%)	2 / 263 (0.76%)	0 / 159 (0%)
Non-small cell lung cancer ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Non-small cell lung cancer metastatic ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Pericardial effusion malignant ^{† A}	5 / 267 (1.87%)	2 / 263 (0.76%)	0 / 159 (0%)
Tumour associated fever ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Tumour pain ^{† A}	4 / 267 (1.5%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Nervous system disorders
Aphasia ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Ataxia ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Cerebral infarction ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Cerebrovascular accident ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	0 / 159 (0%)
Cubital tunnel syndrome ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Depressed level of consciousness ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Epilepsy ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Headache ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
IIIrd nerve paresis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Ischaemic stroke ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Loss of consciousness ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Malignant spinal cord compression ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Muscle spasticity ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Nervous system disorder ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Peripheral motor neuropathy ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Presyncope ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Seizure ^{† A}	4 / 267 (1.5%)	3 / 263 (1.14%)	1 / 159 (0.63%)
Spinal cord compression ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Syncope ^{† A}	4 / 267 (1.5%)	3 / 263 (1.14%)	0 / 159 (0%)
VIth nerve paresis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Vocal cord paralysis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Product Issues
Device occlusion ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Psychiatric disorders
Alcohol withdrawal syndrome ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Confusional state ^{† A}	3 / 267 (1.12%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Disorientation ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Mental status changes ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Organic brain syndrome ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Psychotic disorder ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Suicide attempt ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Renal and urinary disorders
Acute kidney injury ^{† A}	2 / 267 (0.75%)	0 / 263 (0%)	0 / 159 (0%)
Haematuria ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Hydronephrosis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Oliguria ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Renal failure ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Renal infarct ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Tubulointerstitial nephritis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Aspiration ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Asthma ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Atelectasis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Bronchial obstruction ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Chronic obstructive pulmonary disease ^{† A}	3 / 267 (1.12%)	7 / 263 (2.66%)	1 / 159 (0.63%)
Cough ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Dyspnoea ^{† A}	6 / 267 (2.25%)	9 / 263 (3.42%)	5 / 159 (3.14%)
Dyspnoea exertional ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Eosinophilic pneumonia ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Haemoptysis ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Haemothorax ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Hypoxia ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Interstitial lung disease ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Laryngeal haemorrhage ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Lung infiltration ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Mediastinal disorder ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Obstructive airways disorder ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pleural effusion ^{† A}	8 / 267 (3%)	5 / 263 (1.9%)	3 / 159 (1.89%)
Pleuritic pain ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Pneumonitis ^{† A}	9 / 267 (3.37%)	2 / 263 (0.76%)	1 / 159 (0.63%)
Pneumothorax ^{† A}	4 / 267 (1.5%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Pulmonary embolism ^{† A}	8 / 267 (3%)	11 / 263 (4.18%)	5 / 159 (3.14%)
Pulmonary haemorrhage ^{† A}	2 / 267 (0.75%)	1 / 263 (0.38%)	0 / 159 (0%)
Pulmonary mass ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pulmonary microemboli ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Pulmonary oedema ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Respiratory failure ^{† A}	4 / 267 (1.5%)	2 / 263 (0.76%)	2 / 159 (1.26%)
Skin and subcutaneous tissue disorders
Rash ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Rash maculo-papular ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Rash papular ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Stevens-Johnson syndrome ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Vascular disorders
Air embolism ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Aortic aneurysm rupture ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Circulatory collapse ^{† A}	0 / 267 (0%)	3 / 263 (1.14%)	1 / 159 (0.63%)
Deep vein thrombosis ^{† A}	3 / 267 (1.12%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Embolism ^{† A}	0 / 267 (0%)	4 / 263 (1.52%)	1 / 159 (0.63%)
Extremity necrosis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Hypotension ^{† A}	1 / 267 (0.37%)	1 / 263 (0.38%)	0 / 159 (0%)
Iliac artery occlusion ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Jugular vein thrombosis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Leriche syndrome ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Lymphoedema ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	1 / 159 (0.63%)
Peripheral artery thrombosis ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Peripheral ischaemia ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Superior vena cava syndrome ^{† A}	0 / 267 (0%)	2 / 263 (0.76%)	0 / 159 (0%)
Vascular occlusion ^{† A}	0 / 267 (0%)	1 / 263 (0.38%)	0 / 159 (0%)
Vein disorder ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
Venous thrombosis ^{† A}	1 / 267 (0.37%)	0 / 263 (0%)	0 / 159 (0%)
†Indicates events were collected by systematic assessment. ATerm from vocabulary, 25.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab	Investigator Choice of Chemotherapy	Post Chemotherapy Optional Nivolumab
	Affected / At Risk (%)	Affected / At Risk (%)	Affected / At Risk (%)
Total	245 / 267 (91.76%)	252 / 263 (95.82%)	137 / 159 (86.16%)
Blood and lymphatic system disorders
Anaemia ^{† A}	54 / 267 (20.22%)	142 / 263 (53.99%)	38 / 159 (23.9%)
Leukopenia ^{† A}	1 / 267 (0.37%)	17 / 263 (6.46%)	1 / 159 (0.63%)
Neutropenia ^{† A}	5 / 267 (1.87%)	54 / 263 (20.53%)	4 / 159 (2.52%)
Thrombocytopenia ^{† A}	5 / 267 (1.87%)	40 / 263 (15.21%)	4 / 159 (2.52%)
Endocrine disorders
Hypothyroidism ^{† A}	23 / 267 (8.61%)	23 / 263 (8.75%)	14 / 159 (8.81%)
Eye disorders
Lacrimation increased ^{† A}	3 / 267 (1.12%)	21 / 263 (7.98%)	1 / 159 (0.63%)
Gastrointestinal disorders
Abdominal pain ^{† A}	35 / 267 (13.11%)	32 / 263 (12.17%)	12 / 159 (7.55%)
Abdominal pain upper ^{† A}	11 / 267 (4.12%)	23 / 263 (8.75%)	9 / 159 (5.66%)
Constipation ^{† A}	65 / 267 (24.34%)	84 / 263 (31.94%)	24 / 159 (15.09%)
Diarrhoea ^{† A}	84 / 267 (31.46%)	82 / 263 (31.18%)	29 / 159 (18.24%)
Dry mouth ^{† A}	13 / 267 (4.87%)	12 / 263 (4.56%)	8 / 159 (5.03%)
Dyspepsia ^{† A}	19 / 267 (7.12%)	13 / 263 (4.94%)	2 / 159 (1.26%)
Nausea ^{† A}	86 / 267 (32.21%)	149 / 263 (56.65%)	36 / 159 (22.64%)
Stomatitis ^{† A}	13 / 267 (4.87%)	20 / 263 (7.6%)	5 / 159 (3.14%)
Vomiting ^{† A}	59 / 267 (22.1%)	77 / 263 (29.28%)	16 / 159 (10.06%)
General disorders
Asthenia ^{† A}	26 / 267 (9.74%)	41 / 263 (15.59%)	13 / 159 (8.18%)
Chest pain ^{† A}	9 / 267 (3.37%)	25 / 263 (9.51%)	9 / 159 (5.66%)
Chills ^{† A}	18 / 267 (6.74%)	18 / 263 (6.84%)	6 / 159 (3.77%)
Fatigue ^{† A}	108 / 267 (40.45%)	134 / 263 (50.95%)	47 / 159 (29.56%)
Malaise ^{† A}	15 / 267 (5.62%)	14 / 263 (5.32%)	5 / 159 (3.14%)
Mucosal inflammation ^{† A}	7 / 267 (2.62%)	23 / 263 (8.75%)	3 / 159 (1.89%)
Non-cardiac chest pain ^{† A}	25 / 267 (9.36%)	21 / 263 (7.98%)	11 / 159 (6.92%)
Oedema peripheral ^{† A}	35 / 267 (13.11%)	67 / 263 (25.48%)	21 / 159 (13.21%)
Pain ^{† A}	14 / 267 (5.24%)	12 / 263 (4.56%)	9 / 159 (5.66%)
Pyrexia ^{† A}	37 / 267 (13.86%)	55 / 263 (20.91%)	22 / 159 (13.84%)
Infections and infestations
Bronchitis ^{† A}	13 / 267 (4.87%)	19 / 263 (7.22%)	10 / 159 (6.29%)
Nasopharyngitis ^{† A}	19 / 267 (7.12%)	20 / 263 (7.6%)	10 / 159 (6.29%)
Pneumonia ^{† A}	25 / 267 (9.36%)	23 / 263 (8.75%)	9 / 159 (5.66%)
Upper respiratory tract infection ^{† A}	24 / 267 (8.99%)	24 / 263 (9.13%)	9 / 159 (5.66%)
Urinary tract infection ^{† A}	14 / 267 (5.24%)	13 / 263 (4.94%)	4 / 159 (2.52%)
Injury, poisoning and procedural complications
Fall ^{† A}	15 / 267 (5.62%)	11 / 263 (4.18%)	5 / 159 (3.14%)
Investigations
Alanine aminotransferase increased ^{† A}	31 / 267 (11.61%)	30 / 263 (11.41%)	13 / 159 (8.18%)
Aspartate aminotransferase increased ^{† A}	39 / 267 (14.61%)	28 / 263 (10.65%)	10 / 159 (6.29%)
Blood alkaline phosphatase increased ^{† A}	22 / 267 (8.24%)	18 / 263 (6.84%)	7 / 159 (4.4%)
Blood creatinine increased ^{† A}	13 / 267 (4.87%)	34 / 263 (12.93%)	17 / 159 (10.69%)
Gamma-glutamyltransferase increased ^{† A}	10 / 267 (3.75%)	14 / 263 (5.32%)	4 / 159 (2.52%)
Lymphocyte count decreased ^{† A}	18 / 267 (6.74%)	18 / 263 (6.84%)	5 / 159 (3.14%)
Neutrophil count decreased ^{† A}	9 / 267 (3.37%)	43 / 263 (16.35%)	4 / 159 (2.52%)
Platelet count decreased ^{† A}	12 / 267 (4.49%)	38 / 263 (14.45%)	1 / 159 (0.63%)
Weight decreased ^{† A}	42 / 267 (15.73%)	37 / 263 (14.07%)	12 / 159 (7.55%)
White blood cell count decreased ^{† A}	7 / 267 (2.62%)	33 / 263 (12.55%)	6 / 159 (3.77%)
Metabolism and nutrition disorders
Decreased appetite ^{† A}	91 / 267 (34.08%)	102 / 263 (38.78%)	37 / 159 (23.27%)
Dehydration ^{† A}	10 / 267 (3.75%)	19 / 263 (7.22%)	7 / 159 (4.4%)
Hyperglycaemia ^{† A}	19 / 267 (7.12%)	18 / 263 (6.84%)	10 / 159 (6.29%)
Hyperkalaemia ^{† A}	15 / 267 (5.62%)	19 / 263 (7.22%)	11 / 159 (6.92%)
Hypoalbuminaemia ^{† A}	28 / 267 (10.49%)	27 / 263 (10.27%)	11 / 159 (6.92%)
Hypokalaemia ^{† A}	24 / 267 (8.99%)	31 / 263 (11.79%)	13 / 159 (8.18%)
Hypomagnesaemia ^{† A}	16 / 267 (5.99%)	49 / 263 (18.63%)	19 / 159 (11.95%)
Hyponatraemia ^{† A}	28 / 267 (10.49%)	37 / 263 (14.07%)	13 / 159 (8.18%)
Hypophosphataemia ^{† A}	6 / 267 (2.25%)	17 / 263 (6.46%)	6 / 159 (3.77%)
Musculoskeletal and connective tissue disorders
Arthralgia ^{† A}	53 / 267 (19.85%)	47 / 263 (17.87%)	29 / 159 (18.24%)
Back pain ^{† A}	42 / 267 (15.73%)	62 / 263 (23.57%)	23 / 159 (14.47%)
Muscle spasms ^{† A}	9 / 267 (3.37%)	14 / 263 (5.32%)	10 / 159 (6.29%)
Muscular weakness ^{† A}	17 / 267 (6.37%)	26 / 263 (9.89%)	9 / 159 (5.66%)
Musculoskeletal chest pain ^{† A}	18 / 267 (6.74%)	13 / 263 (4.94%)	5 / 159 (3.14%)
Myalgia ^{† A}	28 / 267 (10.49%)	28 / 263 (10.65%)	10 / 159 (6.29%)
Pain in extremity ^{† A}	23 / 267 (8.61%)	31 / 263 (11.79%)	11 / 159 (6.92%)
Nervous system disorders
Dizziness ^{† A}	30 / 267 (11.24%)	41 / 263 (15.59%)	21 / 159 (13.21%)
Dysgeusia ^{† A}	14 / 267 (5.24%)	25 / 263 (9.51%)	7 / 159 (4.4%)
Headache ^{† A}	30 / 267 (11.24%)	50 / 263 (19.01%)	19 / 159 (11.95%)
Neuropathy peripheral ^{† A}	5 / 267 (1.87%)	15 / 263 (5.7%)	8 / 159 (5.03%)
Peripheral sensory neuropathy ^{† A}	7 / 267 (2.62%)	24 / 263 (9.13%)	7 / 159 (4.4%)
Psychiatric disorders
Anxiety ^{† A}	17 / 267 (6.37%)	18 / 263 (6.84%)	12 / 159 (7.55%)
Depression ^{† A}	14 / 267 (5.24%)	13 / 263 (4.94%)	4 / 159 (2.52%)
Insomnia ^{† A}	24 / 267 (8.99%)	40 / 263 (15.21%)	18 / 159 (11.32%)
Respiratory, thoracic and mediastinal disorders
Cough ^{† A}	77 / 267 (28.84%)	79 / 263 (30.04%)	37 / 159 (23.27%)
Dysphonia ^{† A}	12 / 267 (4.49%)	21 / 263 (7.98%)	3 / 159 (1.89%)
Dyspnoea ^{† A}	69 / 267 (25.84%)	75 / 263 (28.52%)	38 / 159 (23.9%)
Epistaxis ^{† A}	8 / 267 (3%)	22 / 263 (8.37%)	4 / 159 (2.52%)
Haemoptysis ^{† A}	17 / 267 (6.37%)	20 / 263 (7.6%)	8 / 159 (5.03%)
Oropharyngeal pain ^{† A}	8 / 267 (3%)	15 / 263 (5.7%)	5 / 159 (3.14%)
Pleural effusion ^{† A}	8 / 267 (3%)	16 / 263 (6.08%)	9 / 159 (5.66%)
Pneumonitis ^{† A}	12 / 267 (4.49%)	17 / 263 (6.46%)	15 / 159 (9.43%)
Productive cough ^{† A}	30 / 267 (11.24%)	25 / 263 (9.51%)	8 / 159 (5.03%)
Skin and subcutaneous tissue disorders
Alopecia ^{† A}	9 / 267 (3.37%)	26 / 263 (9.89%)	3 / 159 (1.89%)
Dry skin ^{† A}	22 / 267 (8.24%)	26 / 263 (9.89%)	14 / 159 (8.81%)
Pruritus ^{† A}	39 / 267 (14.61%)	31 / 263 (11.79%)	17 / 159 (10.69%)
Rash ^{† A}	39 / 267 (14.61%)	37 / 263 (14.07%)	20 / 159 (12.58%)
Rash maculo-papular ^{† A}	18 / 267 (6.74%)	12 / 263 (4.56%)	6 / 159 (3.77%)
Vascular disorders
Hypertension ^{† A}	18 / 267 (6.74%)	19 / 263 (7.22%)	8 / 159 (5.03%)
Hypotension ^{† A}	9 / 267 (3.37%)	14 / 263 (5.32%)	8 / 159 (5.03%)
†Indicates events were collected by systematic assessment. ATerm from vocabulary, 25.0

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 the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact:
Name/Official Title:	Bristol-Myers Squibb Study Director
Organization:	Bristol-Myers Squibb
Phone:	Please Email
Email:	Clinical.Trials@bms.com