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)

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02041533
• Collaborator: Ono Pharmaceutical Co. Ltd (Industry)
• Enrollment: 1,325
• Locations: 141
• Arms: 2
• Actual Duration (Months): 98
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.1

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Stage IV or Recurrent Non-Small Cell Lung Cancer	Biological: Nivolumab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1325 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 27, 2014
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: May 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Primary Outcome Measures

1. Progression-Free Survival in Participants With PD-L1 Expression >= 5% [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 [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% [From date of randomization to date of death (assessed up to August 2016, approximately 28 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 [From date of randomization to date of death (assessed up to August 2016, approximately 28 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% [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. Duration of Response in Participants With PD-L1 Expression>= 5% [From date of first confirmed response to date of tumor progression (Assessed up to August 2016, approximately 28 months)]

   Duration of Response (DOR) was summarized for participants with objective response and was defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression as determined by IRRC assessment (per RECIST v1.1) or death due to any cause, whichever occurs first. DOR censoring rules were the same as the PFS primary definition. 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

6. Time to Response in Participants With PD-L1 Expression >= 5% [From date of randomization to date of first confirmed response (assessed up to August 2016, approximately 18 months)]

   Time to Response (TTR) was defined as the time from randomization to the date of the first response (CR or PR), as assessed by IRRC assessment. TTR was evaluated for responders only. 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.

7. Disease-related Symptom Improvement Rate by Week 12 [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 Criteria

Criteria

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

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 and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Cancer Center, Inc.	Mobile	Alabama	United States	36608
2	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
3	Arizona Oncol Assoc Dba (Hem Onc Physicians&Extenders) Hope	Tucson	Arizona	United States	85704
4	Stanford Cancer Institute	Stanford	California	United States	94305-5826
5	University Of Colorado Hosp	Aurora	Colorado	United States	80045
6	Yale University	New Haven	Connecticut	United States	06520
7	Baptist Health Medical Group Oncology	Miami	Florida	United States	33176
8	Ocala Oncology Center	Ocala	Florida	United States	34471
9	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
10	Local Institution - 0010	Atlanta	Georgia	United States	30322
11	Northwest Georgia Oncology Center, P.C.	Marietta	Georgia	United States	30060
12	Rush University Med Ctr	Chicago	Illinois	United States	60612-3841
13	Baptist Health Lexington	Lexington	Kentucky	United States	40503
14	Crescent City Research Consortium, LLC	Marrero	Louisiana	United States	70072
15	Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins	Baltimore	Maryland	United States	21287
16	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
17	Beth Israel Deaconess Medical Center.	Boston	Massachusetts	United States	02215
18	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
19	New York University Clinical Cancer Center	New York	New York	United States	10016
20	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
21	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina	United States	27599-7305
22	Duke University	Durham	North Carolina	United States	27710
23	University Hospitals	Cleveland	Ohio	United States	44106
24	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
25	Oregon Health & Science University	Portland	Oregon	United States	97239-3098
26	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
27	University Of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
28	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
29	UPMC Cancer Center	Pittsburgh	Pennsylvania	United States	15232
30	Local Institution - 0011	Charleston	South Carolina	United States	29425
31	Local Institution - 0038	Greenville	South Carolina	United States	29601
32	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-6307
33	University Of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
34	Univ Of Tx. Md Anderson	Houston	Texas	United States	77030
35	Cancer Centers of South Texas	San Antonio	Texas	United States	78212
36	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington	United States	98902
37	COIBA	Berazategui	Buenos Aires	Argentina	1880
38	Instituto Medico Especializado Alexander Fleming	Capital Federal	Buenos Aires	Argentina	1426
39	Local Institution - 0052	Ciudad Autonoma De Buenos Aire	Buenos Aires	Argentina	1181
40	Clinica Colombo	Cordoba		Argentina	5000
41	Instituto Oncologico De Cordoba	Cordoba		Argentina	5000
42	Local Institution	Camperdown	New South Wales	Australia	2050
43	Local Institution	Brisbane	Queensland	Australia	4102
44	Local Institution	Elizabeth Vale	South Australia	Australia	5112
45	Local Institution	Fitzroy	Victoria	Australia	3065
46	Local Institution	Heidelberg	Victoria	Australia	3084
47	Local Institution	Wels		Austria	4600
48	Local Institution	Wien		Austria	1090
49	Local Institution	Brussels		Belgium	1090
50	Local Institution	Edegem		Belgium	2650
51	Local Institution	Gent		Belgium	9000
52	Local Institution	Leuven		Belgium	3000
53	Local Institution - 0134	Ijui	Rio Grande Do Sul	Brazil	98700-000
54	Local Institution	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
55	Local Institution	Barretos	Sao Paulo	Brazil	14780-070
56	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
57	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
58	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
59	Centre Hospitalier De L'Universite De Montreal	Montreal	Quebec	Canada	H2X 3E4
60	CISSS du Bas-Saint-Laurent Hopital Regional de Rimouski	Rimouski	Quebec	Canada	G5L 5T1
61	Local Institution	Olomouc		Czechia	779 00
62	Local Institution	Ostrava - Poruba		Czechia	708 52
63	Local Institution	Praha 8		Czechia	180 81
64	Local Institution	Usti nad Labem		Czechia	401 13
65	Local Institution - 0120	Helsinki		Finland	00029
66	Local Institution - 0119	Tampere		Finland	33521
67	Local Institution - 0118	Vaasa		Finland	65130
68	Hopital Cote De Nacre C H U Caen	Caen		France	14000
69	Local Institution	Lille		France	59000
70	Local Institution	Marseille Cedex 20		France	13915
71	Local Institution	Pontoise Cedex		France	95303
72	Local Institution	Rennes Cedex 9		France	35033
73	Local Institution	Strasbourg		France	67090
74	Sozialstiftung Bamberg	Bamberg		Germany	96049
75	LungenClinic Grosshansdorf GmbH	Grosshansdorf		Germany	22927
76	Thoraxklinik-Heidelberg gGmbH	Heidelberg		Germany	69126
77	Local Institution	Koeln		Germany	50937
78	Klinik Schillerhoehe GmbH	Stuttgart		Germany	70376
79	Local Institution	Wiesbaden		Germany	65199
80	Local Institution - 0073	Heraklion	Creta	Greece	71110
81	Sotiria General Hospital	Athens		Greece	11527
82	Local Institution	Budapest		Hungary	1121
83	Local Institution	Debrecen		Hungary	4032
84	Local Institution	Matrahaza		Hungary	3233
85	Azienda Ospedaliera Moscati	Avellino		Italy	83100
86	Local Institution	Livorno		Italy	57100
87	Local Institution - 0143	Milano		Italy	20141
88	Local Institution - 0142	Napoli		Italy	80131
89	Local Institution	Perugia		Italy	06132
90	Local Institution	Terni		Italy	05100
91	Local Institution	Nagoya	Aichi	Japan	4600001
92	Local Institution	Nagoya	Aichi	Japan	4648681
93	Local Institution	Matsuyama-shi	Ehime	Japan	7910280
94	Local Institution	Kobe City	Hyogo	Japan	6500047
95	Local Institution	Natori-shi	Miyagi	Japan	9811293
96	Local Institution - 0151	Niigata-shi	Niigata	Japan	951-8566
97	Local Institution	Habikino-city	Osaka	Japan	5838588
98	Local Institution	Miyakojima-ku	Osaka	Japan	534-0021
99	Local Institution	Osaka-sayama	Osaka	Japan	589-8511
100	Local Institution	Sakai-shi	Osaka	Japan	591-8555
101	Local Institution	Kitaadachi-gun	Saitama	Japan	3620806
102	Local Institution	Sunto-gun	Shizuoka	Japan	4118777
103	Local Institution	Chuo-ku	Tokyo	Japan	1040045
104	Local Institution	Akashi, Hyogo		Japan	673-8558
105	Local Institution	Ota, Gunma		Japan	3738550
106	Local Institution	Sapporo, Hokkaido		Japan	062-0931
107	Local Institution	Tokyo		Japan	1358550
108	Local Institution	Wakayama		Japan	641-8510
109	Local Institution	Seoul		Korea, Republic of	03722
110	Local Institution	Seoul		Korea, Republic of	135-710
111	Local Institution	Seoul		Korea, Republic of
112	Local Institution - 0117	Mexico	Distrito Federal	Mexico	14080
113	Local Institution	Guadalajara	Jalisco	Mexico	44280
114	Local Institution	Merida	Yucatan	Mexico	97133
115	Local Institution	Amsterdam		Netherlands	1066 CX
116	Local Institution	Groningen		Netherlands	9713 GZ
117	Local Institution	Rotterdam		Netherlands	3014 GD
118	Local Institution	Bydgoszcz		Poland	85-796
119	Local Institution	Krakow		Poland	31-202
120	Local Institution	Lodz		Poland	93-513
121	Local Institution	Warszawa		Poland	02-781
122	Local Institution	Wodzislaw Slaski		Poland	44-300
123	Local Institution - 0068	Cluj Napoca		Romania	400015
124	Local Institution	Cluj-napoca		Romania	400352
125	Local Institution	Ploiesti		Romania	100337
126	Local Institution	Barcelona		Spain	08035
127	Local Institution - 0041	Las Palmas De Gran Canaria		Spain	35016
128	Local Institution	Madrid		Spain	28050
129	Local Institution	Malaga		Spain	29010
130	Local Institution	Sevilla		Spain	41013
131	Local Institution	Valencia		Spain	46014
132	Local Institution	Stockholm		Sweden	171 76
133	Local Institution - 0125	Uppsala		Sweden	751 85
134	Local Institution	Chur		Switzerland	7000
135	Local Institution	Lausanne		Switzerland	1011
136	Local Institution	Zuerich		Switzerland	8091
137	Local Institution	Taipei		Taiwan	11217
138	Local Institution	Kayseri		Turkey	38039
139	Local Institution - 0098	London	Greater London	United Kingdom	N18 1QX
140	Local Institution	Manchester	Greater Manchester	United Kingdom	M20 4XB
141	Local Institution	Leeds	Yorkshire	United Kingdom	LS9 7TF

Sponsors and Collaborators

• Bristol-Myers Squibb
• Ono Pharmaceutical Co. Ltd

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02041533
• Other Study ID Numbers: CA209-026; 2012-004502-93
• First Posted: Jan 22, 2014
• Last Update Posted: Jul 26, 2022
• Last Verified: Jul 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; Carcinoma, Non-Small-Cell Lung; Recurrence; Gemcitabine; Paclitaxel; Carboplatin; Nivolumab; Pemetrexed

Study Results

Participant Flow

Pre-assignment Detail	1325 participants were enrolled; 541 were randomized to a treatment group; 530 were treated. Participants were randomized but not treated due to disease progression (n=2), withdrawal of consent (n=5), or they no longer met study criteria (n=4)

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	Investigators' choice of chemotherapy was 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).
Period Title: Overall Study
STARTED	271	270
Began Treatment	267	263
COMPLETED	43	12
NOT COMPLETED	228	258

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	Investigators' choice of chemotherapy was 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).	Total of all reporting groups
Overall Participants	271	270	541
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (10.25)	63.4 (9.63)	63.1 (9.94)
Sex: Female, Male (Count of Participants)
Female	87 32.1%	122 45.2%	209 38.6%
Male	184 67.9%	148 54.8%	332 61.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 1.5%	3 1.1%	7 1.3%
Not Hispanic or Latino	141 52%	139 51.5%	280 51.8%
Unknown or Not Reported	126 46.5%	128 47.4%	254 47%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Asian	30 11.1%	17 6.3%	47 8.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 2.2%	10 3.7%	16 3%
White	228 84.1%	242 89.6%	470 86.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 2.2%	1 0.4%	7 1.3%

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	Investigators' choice of chemotherapy was 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).
Measure Participants	211	212
Median (95% Confidence Interval) [months]	4.21	5.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2511
	Comments
	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
	Parameter Dispersion	Type: Value:
	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	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

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	Investigators' choice of chemotherapy was 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).
Measure Participants	271	270
Median (95% Confidence Interval) [months]	4.21	5.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.43
	Parameter Dispersion	Type: Value:
	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 (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	Investigators' choice of chemotherapy was 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).
Measure Participants	211	212
Median (95% Confidence Interval) [months]	14.36	13.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.30
	Parameter Dispersion	Type: Value:
	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	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 (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	Investigators' choice of chemotherapy was 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).
Measure Participants	271	270
Median (95% Confidence Interval) [months]	13.73	13.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.33
	Parameter Dispersion	Type: Value:
	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	Investigators' choice of chemotherapy was 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).
Measure Participants	211	212
Number (95% Confidence Interval) [Percentage of participants]	26.1 9.6%	33.5 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Investigator Choice of Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.06
	Parameter Dispersion	Type: Value:
	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	Duration of Response in Participants With PD-L1 Expression>= 5%
Description	Duration of Response (DOR) was summarized for participants with objective response and was defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression as determined by IRRC assessment (per RECIST v1.1) or death due to any cause, whichever occurs first. DOR censoring rules were the same as the PFS primary definition. 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 first confirmed response to date of tumor progression (Assessed up to August 2016, approximately 28 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with a confirmed response and 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	Investigators' choice of chemotherapy was 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).
Measure Participants	55	71
Median (Full Range) [months]	12.12	5.65

7. Secondary Outcome

Title	Time to Response in Participants With PD-L1 Expression >= 5%
Description	Time to Response (TTR) was defined as the time from randomization to the date of the first response (CR or PR), as assessed by IRRC assessment. TTR was evaluated for responders only. 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 to date of first confirmed response (assessed up to August 2016, approximately 18 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with a confirmed response and 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	Investigators' choice of chemotherapy was 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).
Measure Participants	55	71
Median (Full Range) [months]	2.76	2.56

8. 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	Investigators' choice of chemotherapy was 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).
Measure Participants	271	270
Number (95% Confidence Interval) [Percentage of participants]	35.4 13.1%	33.7 12.5%

Adverse Events

Time Frame	From first dose to date of last dose plus 30 days (assessed up to August 2016, approximately 18 months)
Arm/Group Title	NIVOLUMAB 3 mg/kg		INVESTIGATOR CHOICE
Arm/Group Description
All Cause Mortality
	NIVOLUMAB 3 mg/kg		INVESTIGATOR CHOICE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	NIVOLUMAB 3 mg/kg		INVESTIGATOR CHOICE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	155/267 (58.1%)		115/263 (43.7%)
Blood and lymphatic system disorders
Anaemia	0/267 (0%)		15/263 (5.7%)
Febrile neutropenia	1/267 (0.4%)		6/263 (2.3%)
Leukopenia	0/267 (0%)		1/263 (0.4%)
Neutropenia	0/267 (0%)		3/263 (1.1%)
Pancytopenia	1/267 (0.4%)		3/263 (1.1%)
Thrombocytopenia	0/267 (0%)		6/263 (2.3%)
Cardiac disorders
Acute coronary syndrome	2/267 (0.7%)		1/263 (0.4%)
Acute left ventricular failure	1/267 (0.4%)		0/263 (0%)
Atrial fibrillation	0/267 (0%)		3/263 (1.1%)
Atrial flutter	0/267 (0%)		1/263 (0.4%)
Cardiac arrest	1/267 (0.4%)		0/263 (0%)
Cardiac failure	0/267 (0%)		1/263 (0.4%)
Cardiac failure acute	1/267 (0.4%)		0/263 (0%)
Cardiac failure congestive	1/267 (0.4%)		1/263 (0.4%)
Cardiac tamponade	1/267 (0.4%)		0/263 (0%)
Myocardial infarction	0/267 (0%)		2/263 (0.8%)
Myocardial ischaemia	1/267 (0.4%)		1/263 (0.4%)
Pericardial effusion	0/267 (0%)		1/263 (0.4%)
Sinus bradycardia	1/267 (0.4%)		0/263 (0%)
Endocrine disorders
Adrenal insufficiency	4/267 (1.5%)		2/263 (0.8%)
Eye disorders
Cataract	1/267 (0.4%)		0/263 (0%)
Gastrointestinal disorders
Abdominal pain	0/267 (0%)		2/263 (0.8%)
Colitis	3/267 (1.1%)		0/263 (0%)
Constipation	2/267 (0.7%)		0/263 (0%)
Diarrhoea	7/267 (2.6%)		2/263 (0.8%)
Dysphagia	1/267 (0.4%)		0/263 (0%)
Gastrointestinal haemorrhage	0/267 (0%)		1/263 (0.4%)
Ileus	0/267 (0%)		1/263 (0.4%)
Large intestinal obstruction	0/267 (0%)		1/263 (0.4%)
Nausea	2/267 (0.7%)		3/263 (1.1%)
Oesophagitis	1/267 (0.4%)		0/263 (0%)
Small intestinal obstruction	0/267 (0%)		1/263 (0.4%)
Upper gastrointestinal haemorrhage	1/267 (0.4%)		0/263 (0%)
Vomiting	2/267 (0.7%)		4/263 (1.5%)
General disorders
Asthenia	2/267 (0.7%)		0/263 (0%)
Catheter site pain	0/267 (0%)		1/263 (0.4%)
Chest pain	2/267 (0.7%)		2/263 (0.8%)
Death	1/267 (0.4%)		0/263 (0%)
Fatigue	2/267 (0.7%)		5/263 (1.9%)
General physical health deterioration	3/267 (1.1%)		3/263 (1.1%)
Multiple organ dysfunction syndrome	1/267 (0.4%)		0/263 (0%)
Pain	1/267 (0.4%)		1/263 (0.4%)
Performance status decreased	0/267 (0%)		1/263 (0.4%)
Pyrexia	4/267 (1.5%)		3/263 (1.1%)
Hepatobiliary disorders
Cholecystitis acute	2/267 (0.7%)		0/263 (0%)
Cholestasis	1/267 (0.4%)		1/263 (0.4%)
Hepatic failure	1/267 (0.4%)		0/263 (0%)
Hepatitis	1/267 (0.4%)		0/263 (0%)
Immune system disorders
Hypersensitivity	3/267 (1.1%)		0/263 (0%)
Infections and infestations
Appendicitis	0/267 (0%)		1/263 (0.4%)
Appendicitis perforated	0/267 (0%)		1/263 (0.4%)
Bronchitis	1/267 (0.4%)		2/263 (0.8%)
Cellulitis	0/267 (0%)		1/263 (0.4%)
Diverticulitis	1/267 (0.4%)		0/263 (0%)
Erysipelas	0/267 (0%)		1/263 (0.4%)
Influenza	0/267 (0%)		1/263 (0.4%)
Localised infection	0/267 (0%)		1/263 (0.4%)
Lower respiratory tract infection	2/267 (0.7%)		0/263 (0%)
Lung infection	6/267 (2.2%)		0/263 (0%)
Peritonitis	0/267 (0%)		1/263 (0.4%)
Pneumonia	10/267 (3.7%)		17/263 (6.5%)
Pneumonia bacterial	0/267 (0%)		1/263 (0.4%)
Respiratory tract infection	1/267 (0.4%)		1/263 (0.4%)
Sepsis	4/267 (1.5%)		1/263 (0.4%)
Septic shock	1/267 (0.4%)		1/263 (0.4%)
Skin infection	0/267 (0%)		1/263 (0.4%)
Subcutaneous abscess	1/267 (0.4%)		0/263 (0%)
Upper respiratory tract infection	1/267 (0.4%)		0/263 (0%)
Urinary tract infection	3/267 (1.1%)		0/263 (0%)
Injury, poisoning and procedural complications
Fall	1/267 (0.4%)		1/263 (0.4%)
Femur fracture	0/267 (0%)		2/263 (0.8%)
Hip fracture	2/267 (0.7%)		0/263 (0%)
Infusion related reaction	2/267 (0.7%)		0/263 (0%)
Kyphosis postoperative	0/267 (0%)		1/263 (0.4%)
Lumbar vertebral fracture	0/267 (0%)		1/263 (0.4%)
Procedural complication	0/267 (0%)		1/263 (0.4%)
Radiation necrosis	1/267 (0.4%)		0/263 (0%)
Radiation pneumonitis	1/267 (0.4%)		0/263 (0%)
Upper limb fracture	0/267 (0%)		1/263 (0.4%)
Investigations
Alanine aminotransferase increased	5/267 (1.9%)		0/263 (0%)
Aspartate aminotransferase increased	6/267 (2.2%)		0/263 (0%)
Blood alkaline phosphatase increased	1/267 (0.4%)		0/263 (0%)
Blood bilirubin increased	1/267 (0.4%)		0/263 (0%)
Blood creatinine increased	1/267 (0.4%)		1/263 (0.4%)
C-reactive protein increased	0/267 (0%)		1/263 (0.4%)
Gamma-glutamyltransferase increased	2/267 (0.7%)		0/263 (0%)
Haemoglobin decreased	0/267 (0%)		1/263 (0.4%)
Transaminases increased	1/267 (0.4%)		1/263 (0.4%)
Metabolism and nutrition disorders
Dehydration	4/267 (1.5%)		2/263 (0.8%)
Hypercalcaemia	3/267 (1.1%)		0/263 (0%)
Hyperglycaemia	2/267 (0.7%)		0/263 (0%)
Hypoglycaemia	1/267 (0.4%)		0/263 (0%)
Hypokalaemia	1/267 (0.4%)		0/263 (0%)
Hyponatraemia	4/267 (1.5%)		1/263 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	2/267 (0.7%)		0/263 (0%)
Bone pain	1/267 (0.4%)		2/263 (0.8%)
Osteolysis	0/267 (0%)		1/263 (0.4%)
Pathological fracture	2/267 (0.7%)		0/263 (0%)
Polyarthritis	1/267 (0.4%)		0/263 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	4/267 (1.5%)		1/263 (0.4%)
Haemangioblastoma	1/267 (0.4%)		0/263 (0%)
Lung neoplasm malignant	2/267 (0.7%)		0/263 (0%)
Malignant melanoma	0/267 (0%)		1/263 (0.4%)
Malignant neoplasm of spinal cord	1/267 (0.4%)		0/263 (0%)
Malignant neoplasm progression	35/267 (13.1%)		12/263 (4.6%)
Malignant pleural effusion	4/267 (1.5%)		2/263 (0.8%)
Metastases to central nervous system	2/267 (0.7%)		2/263 (0.8%)
Metastases to meninges	1/267 (0.4%)		0/263 (0%)
Metastases to spine	3/267 (1.1%)		0/263 (0%)
Non-small cell lung cancer	1/267 (0.4%)		0/263 (0%)
Pericardial effusion malignant	5/267 (1.9%)		1/263 (0.4%)
Tumour pain	4/267 (1.5%)		0/263 (0%)
Nervous system disorders
Aphasia	1/267 (0.4%)		0/263 (0%)
Ataxia	0/267 (0%)		1/263 (0.4%)
Cerebrovascular accident	2/267 (0.7%)		1/263 (0.4%)
Depressed level of consciousness	1/267 (0.4%)		0/263 (0%)
Epilepsy	1/267 (0.4%)		0/263 (0%)
Headache	1/267 (0.4%)		0/263 (0%)
Loss of consciousness	0/267 (0%)		1/263 (0.4%)
Muscle spasticity	1/267 (0.4%)		0/263 (0%)
Presyncope	0/267 (0%)		1/263 (0.4%)
Seizure	2/267 (0.7%)		1/263 (0.4%)
Spinal cord compression	0/267 (0%)		1/263 (0.4%)
Syncope	2/267 (0.7%)		3/263 (1.1%)
Vocal cord paralysis	0/267 (0%)		1/263 (0.4%)
Psychiatric disorders
Confusional state	2/267 (0.7%)		1/263 (0.4%)
Mental status changes	1/267 (0.4%)		0/263 (0%)
Psychotic disorder	1/267 (0.4%)		0/263 (0%)
Suicide attempt	1/267 (0.4%)		0/263 (0%)
Renal and urinary disorders
Acute kidney injury	1/267 (0.4%)		0/263 (0%)
Haematuria	1/267 (0.4%)		0/263 (0%)
Renal failure	2/267 (0.7%)		0/263 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/267 (0%)		1/263 (0.4%)
Atelectasis	1/267 (0.4%)		0/263 (0%)
Bronchial obstruction	0/267 (0%)		1/263 (0.4%)
Chronic obstructive pulmonary disease	3/267 (1.1%)		6/263 (2.3%)
Dyspnoea	3/267 (1.1%)		3/263 (1.1%)
Eosinophilic pneumonia	1/267 (0.4%)		0/263 (0%)
Haemoptysis	0/267 (0%)		1/263 (0.4%)
Haemothorax	0/267 (0%)		1/263 (0.4%)
Interstitial lung disease	1/267 (0.4%)		0/263 (0%)
Mediastinal disorder	1/267 (0.4%)		0/263 (0%)
Pleural effusion	6/267 (2.2%)		2/263 (0.8%)
Pleuritic pain	0/267 (0%)		1/263 (0.4%)
Pneumonia aspiration	1/267 (0.4%)		0/263 (0%)
Pneumonitis	7/267 (2.6%)		0/263 (0%)
Pneumothorax	3/267 (1.1%)		0/263 (0%)
Pulmonary embolism	5/267 (1.9%)		5/263 (1.9%)
Pulmonary haemorrhage	2/267 (0.7%)		1/263 (0.4%)
Pulmonary microemboli	1/267 (0.4%)		0/263 (0%)
Pulmonary oedema	0/267 (0%)		1/263 (0.4%)
Respiratory failure	4/267 (1.5%)		0/263 (0%)
Skin and subcutaneous tissue disorders
Rash	1/267 (0.4%)		0/263 (0%)
Rash maculo-papular	1/267 (0.4%)		0/263 (0%)
Rash papular	1/267 (0.4%)		0/263 (0%)
Stevens-johnson syndrome	1/267 (0.4%)		0/263 (0%)
Vascular disorders
Air embolism	1/267 (0.4%)		0/263 (0%)
Aortic aneurysm rupture	1/267 (0.4%)		0/263 (0%)
Circulatory collapse	0/267 (0%)		2/263 (0.8%)
Deep vein thrombosis	3/267 (1.1%)		0/263 (0%)
Embolism	0/267 (0%)		3/263 (1.1%)
Hypotension	1/267 (0.4%)		0/263 (0%)
Iliac artery occlusion	0/267 (0%)		1/263 (0.4%)
Jugular vein thrombosis	1/267 (0.4%)		0/263 (0%)
Peripheral artery thrombosis	0/267 (0%)		1/263 (0.4%)
Superior vena cava syndrome	0/267 (0%)		2/263 (0.8%)
Vascular occlusion	0/267 (0%)		1/263 (0.4%)
Vein disorder	1/267 (0.4%)		0/263 (0%)
Other (Not Including Serious) Adverse Events
	NIVOLUMAB 3 mg/kg		INVESTIGATOR CHOICE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	238/267 (89.1%)		248/263 (94.3%)
Blood and lymphatic system disorders
Anaemia	38/267 (14.2%)		127/263 (48.3%)
Leukopenia	1/267 (0.4%)		16/263 (6.1%)
Neutropenia	2/267 (0.7%)		51/263 (19.4%)
Thrombocytopenia	4/267 (1.5%)		38/263 (14.4%)
Endocrine disorders
Hypothyroidism	20/267 (7.5%)		7/263 (2.7%)
Eye disorders
Lacrimation increased	3/267 (1.1%)		21/263 (8%)
Gastrointestinal disorders
Abdominal pain	26/267 (9.7%)		21/263 (8%)
Constipation	52/267 (19.5%)		68/263 (25.9%)
Diarrhoea	67/267 (25.1%)		60/263 (22.8%)
Dyspepsia	17/267 (6.4%)		11/263 (4.2%)
Nausea	78/267 (29.2%)		134/263 (51%)
Stomatitis	8/267 (3%)		16/263 (6.1%)
Vomiting	54/267 (20.2%)		65/263 (24.7%)
General disorders
Asthenia	21/267 (7.9%)		37/263 (14.1%)
Chest pain	9/267 (3.4%)		14/263 (5.3%)
Chills	16/267 (6%)		12/263 (4.6%)
Fatigue	102/267 (38.2%)		115/263 (43.7%)
Mucosal inflammation	6/267 (2.2%)		21/263 (8%)
Non-cardiac chest pain	24/267 (9%)		10/263 (3.8%)
Oedema peripheral	30/267 (11.2%)		44/263 (16.7%)
Pyrexia	33/267 (12.4%)		39/263 (14.8%)
Infections and infestations
Nasopharyngitis	17/267 (6.4%)		12/263 (4.6%)
Upper respiratory tract infection	18/267 (6.7%)		12/263 (4.6%)
Investigations
Alanine aminotransferase increased	25/267 (9.4%)		18/263 (6.8%)
Aspartate aminotransferase increased	34/267 (12.7%)		18/263 (6.8%)
Blood alkaline phosphatase increased	17/267 (6.4%)		12/263 (4.6%)
Blood creatinine increased	10/267 (3.7%)		18/263 (6.8%)
Lymphocyte count decreased	17/267 (6.4%)		16/263 (6.1%)
Neutrophil count decreased	2/267 (0.7%)		41/263 (15.6%)
Platelet count decreased	4/267 (1.5%)		36/263 (13.7%)
Weight decreased	37/267 (13.9%)		24/263 (9.1%)
White blood cell count decreased	4/267 (1.5%)		29/263 (11%)
Metabolism and nutrition disorders
Decreased appetite	76/267 (28.5%)		81/263 (30.8%)
Hyperglycaemia	15/267 (5.6%)		13/263 (4.9%)
Hypoalbuminaemia	25/267 (9.4%)		19/263 (7.2%)
Hypokalaemia	18/267 (6.7%)		15/263 (5.7%)
Hypomagnesaemia	13/267 (4.9%)		38/263 (14.4%)
Hyponatraemia	24/267 (9%)		25/263 (9.5%)
Hypophosphataemia	7/267 (2.6%)		14/263 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	35/267 (13.1%)		17/263 (6.5%)
Back pain	34/267 (12.7%)		33/263 (12.5%)
Muscular weakness	12/267 (4.5%)		19/263 (7.2%)
Musculoskeletal chest pain	16/267 (6%)		6/263 (2.3%)
Musculoskeletal pain	19/267 (7.1%)		9/263 (3.4%)
Myalgia	26/267 (9.7%)		15/263 (5.7%)
Pain in extremity	17/267 (6.4%)		17/263 (6.5%)
Nervous system disorders
Dizziness	26/267 (9.7%)		25/263 (9.5%)
Dysgeusia	14/267 (5.2%)		24/263 (9.1%)
Headache	24/267 (9%)		31/263 (11.8%)
Peripheral sensory neuropathy	6/267 (2.2%)		18/263 (6.8%)
Psychiatric disorders
Insomnia	17/267 (6.4%)		19/263 (7.2%)
Respiratory, thoracic and mediastinal disorders
Cough	67/267 (25.1%)		49/263 (18.6%)
Dysphonia	9/267 (3.4%)		16/263 (6.1%)
Dyspnoea	64/267 (24%)		40/263 (15.2%)
Epistaxis	5/267 (1.9%)		17/263 (6.5%)
Haemoptysis	15/267 (5.6%)		12/263 (4.6%)
Productive cough	27/267 (10.1%)		14/263 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	5/267 (1.9%)		24/263 (9.1%)
Dry skin	17/267 (6.4%)		11/263 (4.2%)
Pruritus	34/267 (12.7%)		13/263 (4.9%)
Rash	32/267 (12%)		20/263 (7.6%)
Rash maculo-papular	14/267 (5.2%)		7/263 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.