Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02395172
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 792
• Locations: 260
• Arms: 2
• Actual Duration (Months): 56.3
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this study was to demonstrate superiority with regard to overall survival of avelumab versus docetaxel in participants with programmed death ligand 1 (PD-L1) positive, non-small cell lung cancer (NSCLC) after failure of a platinum-based doublet.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Avelumab; Drug: Docetaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 792 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Open-Label, Multicenter Trial of Avelumab (MSB0010718C) Versus Docetaxel in Subjects With Non-Small Cell Lung Cancer That Has Progressed After a Platinum-Containing Doublet
• Actual Study Start Date: Mar 24, 2015
• Actual Primary Completion Date: Nov 22, 2017
• Actual Study Completion Date: Dec 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avelumab	Drug: Avelumab; Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Active Comparator: Docetaxel	Drug: Docetaxel; Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) [Time from date of randomization up to 1420 days]

   The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.

Secondary Outcome Measures

1. Overall Survival (OS) Time in Full Analysis Set Population [Time from date of randomization up to 1420 days]

   The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.

2. Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population [Time from date of randomization up to 907 days]

   PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.

3. Progression-Free Survival (PFS) Time in Full Analysis Set Population [Time from date of randomization up to 907 days]

   PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.

4. Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population [Time from date of randomization up to 907 days]

   Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.

5. Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population [Time from date of randomization up to 907 days]

   Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.

6. Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population [Time from date of randomization up to 907 days]

   Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.

7. Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population [Time from date of randomization up to 907 days]

   Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.

8. Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) [Baseline, End of treatment visit (up to Week 124)]

   The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions).

9. Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) [Baseline, End of treatment visit (up to Week 124)]

   EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.

10. Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) [Baseline, End of treatment visit (up to Week 124)]

    EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.

11. Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) [Baseline, End of treatment visit (up to Week 124)]

    EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).

12. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death [Time from date of randomization up to 1420 days]

    An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

13. Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity [Time from date of randomization up to 1420 days]

    Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event.

14. Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score [Time from date of randomization up to 1420 days]

    ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination.

15. Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab [Time from date of randomization up to 1420 days]

    Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Signed written informed consent before any trial related procedure

• Male or female participants aged greater than or equal to (>=) 18 years

• Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment

• Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory

• Participants with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression

• Participants must have progressed after an acceptable therapy defined as follows:

1. Participants must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR

2. Participants must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease

• Participants with non-squamous cell NSCLC of unknown epidermal growth factor receptor (EGFR) mutation status will require testing (local laboratory, or central laboratory if local testing is not available). Participants with a tumor that harbors an activating EGFR mutation will not be eligible

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry

• Estimated life expectancy of more than 12 weeks

• Adequate hematological function defined by White Blood Cell (WBC) count >= 2.5 × 10^{9/L with absolute neutrophil count (ANC) >= 1.5 × 10}9/L, lymphocyte count >=0.5 × 10^{9/L, platelet count >= 100 × 10}9/L, and hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)

• Adequate hepatic function defined by a total bilirubin level less than or equal to (<=) 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels <= 2.5 × ULN for all participants

• Adequate renal function defined by an estimated creatinine clearance > 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method).

Other protocol defined inclusion criteria could apply

Exclusion criteria

• In the United States only, participants with a squamous cell histology will be excluded

• Systemic anticancer therapy administered after disease progression during or following a platinum based combination

• Participants with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Participants of unknown ALK and/or EGFR mutation status will require testing at screening (local laboratory, or central laboratory if local testing is not available)

• Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4).

• Concurrent anticancer treatment

• Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the participant has not fully recovered from the surgery within 4 weeks of randomization

• Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment.

• All participants with brain metastases, except those meeting the following criteria:

1. Brain metastases have been treated locally, and

2. No ongoing neurological symptoms that are related to the brain localization of the disease

• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

1. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible

2. Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to (<=)10 milligram (mg) or equivalent prednisone per day

3. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable

• Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be <=10 mg per day of equivalent prednisone

Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Tuscaloosa	Alabama	United States	35401
2	Mayo Clinic	Scottsdale , Phoenix	Arizona	United States	85259-5499
3	Pacific Cancer Medical Center, Inc.	Anaheim	California	United States	92801
4	Healing Hands Oncology and Medical Care	Lawndale	California	United States	90260
5	Sutter Gould Medical Foundation	Modesto	California	United States	95355
6	Sharp Memorial Hospital	San Diego	California	United States	92123
7	Lynn Cancer Institute Center	Boca Raton	Florida	United States	33486
8	University Cancer Institute	Boynton Beach	Florida	United States	33426
9	Holy Cross Hospital Inc.	Fort Lauderdale	Florida	United States	33308
10	Florida Cancer Specialists-Broadway	Fort Myers	Florida	United States	33916
11	Florida Cancer Specialists	Saint Petersburg	Florida	United States	33705
12	Florida Cancer Specialists	West Palm Beach	Florida	United States	33401
13	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
14	Metairie Oncologist, LLC	Metairie	Louisiana	United States	70006
15	Henry Ford Health System	Detroit	Michigan	United States	48202
16	Hematology Oncology Associates of Rockland	Nyack	New York	United States	10960
17	Novant Health Oncology Specialists	Winston-Salem	North Carolina	United States	27103
18	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
19	Signal Point Clinical Research Center	Middletown	Ohio	United States	45042
20	Mercy Clinic Oklahoma Communities, Inc.	Oklahoma City	Oklahoma	United States	73120-9309
21	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
22	Penn State Univ. Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
23	Center for Biomedical Research, LLC	Knoxville	Tennessee	United States	37909
24	SCRI - Tennessee Oncology	Nashville	Tennessee	United States	37203
25	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States	76104
26	University of Texas Health Science Center at Tyler	Tyler	Texas	United States	75708
27	MultiCare Health System	Tacoma	Washington	United States	98405
28	Hospital Italiano Regional del Sur	Bahia Blanca		Argentina	B8001HXM
29	Clínica Universitaria Privada Reina Fabiola	Barrio General Paz		Argentina	X5004FHP
30	Centro de Oncologia e Investigacion Buenos Aires	Berazategui		Argentina	B1880BBF
31	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma Buenos Aires		Argentina	C1426ANZ
32	CEMIC	Ciudad Autonoma Buenos Aires		Argentina	C1431FWO
33	Instituto DAMIC Fundacion Rusculleda	Cordoba		Argentina	X5003DCE
34	Centro Oncologico Riojano Integral (Cori)	La Rioja		Argentina	F5300COE
35	Centro Oncologico de Parana	Parana		Argentina	3100
36	Hospital Universitario Austral	Pilar		Argentina	B1629ODT
37	Instituto Gamma	Rosario		Argentina	S2000CRF
38	Sanatorio Parque S.A.	Rosario		Argentina	S2000DSV
39	Instituto de Oncología de Rosario	Rosario		Argentina	S2000KZE
40	Centro Medico San Roque S.R.L.	San Miguel de Tucuman		Argentina	4000
41	Ballarat Base Hospital	Ballarat		Australia	3350
42	Box Hill Hospital	Box Hill		Australia	3128
43	Coffs Harbour Base Hospital	Coffs Harbour		Australia	2450
44	Lyell McEwin Hospital	Elizabeth Vale		Australia	5112
45	Greenslopes Private Hospital	Greenslopes		Australia	4120
46	Lismore Base Hospital	Lismore		Australia	2480
47	Royal Melbourne Hospital	Parkville		Australia	3050
48	St John of God Hospital	Subiaco		Australia	6008
49	Princess Alexandra Hospital	Woolloongabba		Australia	4102
50	UZ Antwerpen	Edegem		Belgium	2650
51	Grand Hôpital de Charleroi	Gilly		Belgium	6060
52	UZ Leuven	Leuven		Belgium	3000
53	Centre Hospitalier de l'Ardenne	Libramont		Belgium	6800
54	C. H. U. Sart Tilman	Liège		Belgium	4000
55	AZ Delta	Roeselare		Belgium	8800
56	Cenantron - Centro Avançado de Tratamento Oncológico S/C Ltda	Belo Horizonte		Brazil	30110-921
57	CEPON - Centro de Pesquisas Oncológicas de Santa Catarina	Florianópolis		Brazil	88034-000
58	Hospital de Caridade de Ijuí	Ijuí		Brazil	98700-000
59	Clínica de Neoplasias Litoral Ltda.	Itajaí		Brazil	88310-110
60	CMiP - Centro Mineiro de Pesquisa	Juiz de Fora		Brazil	36010-570
61	Hospital Bruno Born	Lajeado		Brazil	95900-000
62	Liga Norte-Rio-Grandense Contra o Câncer	Natal		Brazil	59075-740
63	Oncosinos - Clínica de Oncologia - Hospital Regina	Novo Hamburgo		Brazil	93510-250
64	CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo	Passo Fundo		Brazil	99010-260
65	Hospital Mãe de Deus	Porto Alegre		Brazil	90110-270
66	Hospital São Lucas da PUCRS	Porto Alegre		Brazil	90610-000
67	COI - Clínicas Oncológicas Integradas	Rio de Janeiro		Brazil	22793-080
68	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo André		Brazil	09060-650
69	IOS - Instituto de Oncologia de Sorocaba "Dr. Gilson Delgado"	Sorocaba		Brazil	18030-075
70	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto		Brazil	15090-000
71	ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira	São Paulo		Brazil	01246-000
72	UMHAT 'Dr. Georgi Stranski', EAD	Pleven		Bulgaria	5800
73	Complex Oncological Center - Plovdiv, EOOD	Plovdiv		Bulgaria	4004
74	MHAT "Serdika", EOOD	Sofia		Bulgaria	1303
75	MHAT 'Tokuda Hospital Sofia', AD	Sofia		Bulgaria	1407
76	Shato, Ead	Sofia		Bulgaria	1756
77	MHAT 'Sv. Marina', EAD	Varna		Bulgaria	9010
78	Instituto de Terapias Oncologicas Providencia	Santiago		Chile	7500000
79	FALP - Fundación Arturo López Pérez	Santiago		Chile	7500921
80	CIEC - Centro Internacional de Estudios Clínicos	Santiago		Chile	8420383
81	Instituto Clinico Oncologico del Sur (ICOS)	Temuco		Chile
82	Centro de Investigaciones Clinicas Viña del Mar	Viña del Mar		Chile	2540364
83	Hospital Clinico Viña del Mar	Viña del Mar		Chile
84	Fundacion Cardioinfantil Instituto de Cardiologia	Bogota		Colombia	110131
85	Instituto Nacional de Cancerologia E.S.E.	Bogota		Colombia	111511
86	Clinica Colsanitas S.A. sede Clinica Universitaria Colombia	Bogota		Colombia
87	Administradora Country S.A.	Bogotá		Colombia
88	Fundación Valle del Lilí	Cali		Colombia	760032
89	Centro Medico Imbanaco	Cali		Colombia	760042
90	Hemato Oncologos S.A.	Cali		Colombia
91	Instituto de Cancerologia S.A.	Medellin		Colombia
92	Hospital Pablo Tobón Uribe	Medellín		Colombia	050034
93	IPS IMAT- Instituto Medico de Alta Tecnologia - Oncomedica S.A.	Monteria		Colombia
94	General Hospital Dubrovnik	Dubrovnik		Croatia	20000
95	General Hospital Zadar	Zadar		Croatia	23000
96	Clinical Hospital Centar "Sestre Milosrdnice"	Zagreb		Croatia	10000
97	University Clinic for Pulmonary Diseases	Zagreb		Croatia	10000
98	Masarykuv onkologicky ustav	Brno		Czechia	65653
99	Nemocnice Novy Jicin a.s.	Novy Jicin		Czechia	74101
100	Multiscan s.r.o.	Pardubice		Czechia	53203
101	Vseobecna fakultni nemocnice V Praze	Praha 2		Czechia	12808
102	Thomayerova nemocnice	Praha 4		Czechia	14059
103	Herlev Hospital	Herlev		Denmark	2730
104	Odense Universitetshospital	Odense C		Denmark	5000
105	ICO - Site Paul Papin	Angers Cedex 9		France	49933
106	CHU Besançon - Hôpital Jean Minjoz	Besancon Cedex		France	25030
107	Clinique Victor Hugo - Centre Jean Bernard	Le Mans Cedex 02		France	72000
108	Hôpital Nord - AP-HM Marseille#	Marseille cedex 20		France	13915
109	Centre Catherine de Sienne	Nantes		France	44202
110	Centre Antoine Lacassagne	Nice cedex 02		France	06189
111	Groupe Hospitalier Sud - Hôpital Haut-Lévêque	Pessac		France	33604
112	CHU Poitiers - Hôpital la Milétrie	Poitiers		France	86021
113	ICO - Site René Gauducheau	Saint Herblain		France	44805
114	CHU Strasbourg - Nouvel Hôpital Civil	Strasbourg		France	67091
115	CHU de Toulouse - Hôpital Larrey	Toulouse		France	31059
116	Semmelweis Egyetem AOK	Budapest		Hungary	1125
117	Uzsoki Utcai Korhaz	Budapest		Hungary	1145
118	Petz Aladar Megyei Oktato Korhaz	Györ		Hungary	9024
119	Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz	Miskolc		Hungary	3529
120	Tudogyogyintezet Torokbalint	Torokbalint		Hungary	2045
121	Soroka Medical Center	Beer Sheva		Israel	84101
122	Assaf Harofeh Medical Center	Beer Yaakov		Israel	70300
123	Rambam Health Care Campus	Haifa		Israel	3109601
124	The Lady Davis Carmel Medical Center	Haifa		Israel	34361
125	Hadassah University Hospital - Ein Kerem	Jerusalem		Israel	9112001
126	Sapir Medical Center, Meir Hospital	Kfar-Saba		Israel	4428164
127	Rabin Medical Center-Beilinson Campus	Petach Tikva		Israel	4941492
128	Chaim Sheba Medical Center	Ramat-Gan		Israel	52621
129	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
130	Azienda Ospedaliera Istituti Ospitalieri di Cremona	Cremona		Italy	26100
131	Ospedale Mater Salutis	Legnago (VR)		Italy	37045
132	Ospedale Versilia	Lido di Camaiore		Italy	55043
133	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
134	IEO Istituto Europeo di Oncologia	Milano		Italy	20141
135	Seconda Università degli Studi di Napoli	Napoli		Italy	80131
136	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56124
137	Università Campus Bio-Medico di Roma	Roma		Italy	00128
138	Istituto Nazionale Tumori Regina Elena IRCCS	Roma		Italy	00144
139	Policlinico Universitario Agostino Gemelli	Roma		Italy	00168
140	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma		Italy	00189
141	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena		Italy	53100
142	Azienda Ospedaliera Ospedale Treviglio-Caravaggio di Treviglio	Treviglio		Italy	24047
143	National Cancer Center Hospital	Chuo-ku		Japan	104-0045
144	NHO Kyushu Cancer Center	Fukuoka-shi		Japan	811-1395
145	Osaka Prefectural Medical Center for Respiratory and Allergic Diseases	Habikino-shi		Japan	583-8588
146	Hiroshima City Hiroshima Citizens Hospital	Hiroshima-shi		Japan	730-8518
147	National Cancer Center Hospital East	Kashiwa-shi		Japan	277-8577
148	Saitama Cancer Center	Kitaadachi-gun		Japan	362-0806
149	Institute of Biomedical Research and Innovation Hospital	Kobe-shi		Japan	650-0047
150	Kobe City Hospital Organization Kobe City Medical Center General Hospital	Kobe-shi		Japan	650-0047
151	Cancer Institute Hospital of JFCR	Koto-ku		Japan	135-8550
152	Kurume University Hospital	Kurume-shi		Japan	830-0011
153	Miyagi Cancer Center	Natori-shi		Japan	981-1293
154	Aichi Cancer Center Hospital	Okazaki-shi		Japan	444-0011
155	Osaka City General Hospital	Osaka-shi		Japan	534-0021
156	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka-shi		Japan	537-8511
157	Kinki University Hospital	Osakasayama-shi		Japan	589-8511
158	Kitasato University Hospital	Sagamihara-shi		Japan	252-0375
159	NHO Hokkaido Cancer Center	Sapporo-shi		Japan	003-0804
160	Hokkaido University Hospital	Sapporo-shi		Japan	060-8648
161	Tokyo Medical University Hospital	Shinjuku-ku		Japan	160-0023
162	Toyama University Hospital	Toyama-shi		Japan	930-0194
163	Wakayama Medical University Hospital	Wakayama-shi		Japan	641-8510
164	Yokohama Municipal Citizen's Hospital	Yokohama-shi		Japan	240-8555
165	Kanagawa Cancer Center	Yokohama-shi		Japan	241-8515
166	Chungbuk National University Hospital	Cheongju-si		Korea, Republic of	28644
167	Chonnam National University Hwasun Hospital	Hwasun-gun		Korea, Republic of	519-763
168	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
169	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13620
170	Asan Medical Center	Seoul		Korea, Republic of	05505
171	Samsung Medical Center	Seoul		Korea, Republic of	06351
172	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
173	Korea University Anam Hospital	Seoul		Korea, Republic of	136-705
174	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	137-701
175	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si		Korea, Republic of	16247
176	Phylasis Clinicas Research S de RL de CV	Cuautitlan Izcalli		Mexico	54769
177	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango		Mexico	34000
178	Fundacion Rodolfo Padilla Padilla, A.C.	Leon		Mexico	37000
179	Health Pharma Professional Research S.A. de C.V.	Mexico		Mexico	03810
180	Winsett Rethman S.A. de C.V.	Monterrey		Mexico	64060
181	Centro de Investigacion Clinica Chapultepec S.A. de C.V.	Morelia		Mexico	58260
182	Oaxaca Site Management Organization S.C.	Oaxaca		Mexico	68000
183	Centro Oncologico Estatal ISSEMyM	Toluca		Mexico	50180
184	Clinica Monte Carmelo	Arequipa		Peru	04000
185	Hospital Nacional Almanzor Aguinaga Asenjo	Chiclayo		Peru	14001
186	Hospital Nacional Adolfo Guevara Velasco	Cusco		Peru
187	Clinica San Borja	Lima		Peru	15000
188	Hospital Nacional Guillermo Almenara Irigoyen	Lima		Peru	Lima 13
189	Clínica Ricardo Palma	Lima		Peru	LIMA 27
190	Instituto Nacional de Enfermedades Neoplásicas	Lima		Peru	LIMA 34
191	Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza	Brzozow		Poland	36-200
192	Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej	Jelenia Gora		Poland	58-506
193	Samodzielny Publiczny Szpital Kliniczny nr 5 SUM	Katowice		Poland	40-514
194	Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna	Lodz		Poland	90-242
195	KO-MED Centra Kliniczne Lublin II	Lublin		Poland	20-362
196	SSZZOZ im. Dr Teodora Dunina w Rudce	Mrozy		Poland	05-320
197	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy	Otwock		Poland	05-400
198	Spitalul Judetean de Urgenta Alba Iulia	Alba Iulia		Romania	510077
199	Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia Mare	Baia Mare		Romania	430031
200	Policlinica de Diagnostic Rapid SRL	Brasov		Romania	500152
201	Spitalul Clinic Municipal "Dr. Gavril Curteanu" Oradea	Oradea		Romania	410469
202	Spital Lotus SRL	Ploiesti		Romania	100011
203	S.C Oncocenter Oncologie Clinica S.R.L	Timisoara		Romania	300210
204	SHI "Republican Clinical Oncological Dispensary of HM RT"	Kazan		Russian Federation	420029
205	SHBI Moscow Clinical Scientific Center of Department of Healthcare of Moscow	Moscow		Russian Federation	111123
206	FSBHI Clinical research institute of phthisiopulmonology	Saint Petersburg		Russian Federation	191036
207	Pavlov First Saint Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
208	St. Petersburg SHI "City Clinical Oncology Dispensary"	St. Petersburg		Russian Federation	197022
209	FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"	St. Petersburg		Russian Federation	197758
210	Nemocnica s poliklinikou Sv. Jakuba, n.o. Bardejov	Bardejov		Slovakia	08501
211	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Bratislava		Slovakia	82606
212	Ustredna vojenska nemocnica SNP Ruzomberok- Fakultna nemocnica	Ruzomberok		Slovakia	03426
213	Fakultna nemocnica Trnava	Trnava		Slovakia	91708
214	GVI Cape Gate Oncology Centre	Cape Town		South Africa	7570
215	GVI Rondebosch Oncology Centre	Cape town		South Africa	7700
216	GVI Langenhoven Drive Oncology Centre	Port Elizabeth		South Africa	6045
217	University of Pretoria Oncology Department	Pretoria		South Africa	0002
218	Mary Potter Oncology Centre	Pretoria		South Africa	0181
219	Hospital General Universitario de Alicante	Alicante		Spain	03010
220	ICO Badalona - Hospital Germans Trias i Pujol	Badalona		Spain	08916
221	Hospital Universitari Quiron Dexeus	Barcelona		Spain	08028
222	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
223	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
224	ICO l´Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat		Spain	08908
225	Hospital Universitario Materno-Infantil de Canarias	Las Palmas de Gran Canaria		Spain	35016
226	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
227	Centro Integral Oncologico Clara Campal	Madrid		Spain	28050
228	Hospital Clinico Universitario Virgen de la Victoria	Malaga		Spain	29010
229	Hospital de Mataro	Mataro		Spain	08304
230	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela		Spain	15706
231	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
232	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
233	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
234	Kantonsspital Graubuenden	Chur		Switzerland	7000
235	Taichung Veterans General Hospital	Taichung		Taiwan	40705
236	National Cheng Kung University Hospital	Tainan		Taiwan	704
237	National Taiwan University Hospital	Taipei		Taiwan	100
238	Taipei Veterans General Hospital	Taipei		Taiwan	112
239	Tri-Service General Hospital	Taipei		Taiwan	11490
240	Chang Gung Memorial Hospital, Linkou	Taoyuan County		Taiwan	333
241	Hacettepe University Medical Faculty	Ankara		Turkey	06100
242	Baskent University Ankara Hospital	Ankara		Turkey	06500
243	Ankara University Medical Faculty	Ankara		Turkey
244	Trakya University Medical Faculty	Edirne		Turkey	22030
245	Bezmi Alem Foundation University Medical Faculty Hospital	Istanbul		Turkey	34093
246	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
247	Fatih Universitesi Tip Fakultesi	Istanbul		Turkey	34500
248	Marmara University Pendik Research and Training Center	Istanbul		Turkey	34899
249	Ege University Medical Faculty	Izmir		Turkey	35100
250	Dokuz Eylul University Medicine Faculty	Izmir		Turkey	35340
251	Konya Necmettin Erbakan University Meram Faculty of Medicine	Konya		Turkey	42080
252	Royal Bournemouth General Hospital	Bournemouth		United Kingdom	BH7 7DW
253	Bristol Haematology & Oncology Centre	Bristol		United Kingdom	BS2 8ED
254	Royal Devon and Exeter Hospital (Wonford)	Exeter		United Kingdom	EX2 5DW
255	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 OYN
256	St James's University Hospital	Leeds		United Kingdom	LS9 7TF
257	University College London Hospital	London		United Kingdom	NW1 2BU
258	Derriford Hospital	Plymouth		United Kingdom	PL6 8BQ
259	Mount Vernon Hospital	Stevenage		United Kingdom	SG1 4AB
260	The Clatterbridge Cancer Centre	Wirral		United Kingdom	CH63 4JY

Sponsors and Collaborators

• EMD Serono Research & Development Institute, Inc.
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 11, 2017
• Study Protocol - Jan 10, 2017

More Information

Additional Information:

• Related Info
• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT02395172
• Other Study ID Numbers: 100070-004; 2014-005060-15
• First Posted: Mar 20, 2015
• Last Update Posted: Aug 3, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by EMD Serono Research & Development Institute, Inc.: Avelumab; MSB0010718C; Non-Small Cell Lung Cancer; Anti-PD-L1
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Avelumab

Study Results

Participant Flow

Pre-assignment Detail	First participant signed informed consent: 24 Mar 2015, Clinical data cut-off: 04 March 2019.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Period Title: Overall Study
STARTED	396	396
Treated	393	365
COMPLETED	393	365
NOT COMPLETED	3	31

Baseline Characteristics

Arm/Group Title	Avelumab	Docetaxel	Total
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Total of all reporting groups
Overall Participants	396	396	792
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (9.99)	62.5 (9.65)	62.7 (9.81)
Sex: Female, Male (Count of Participants)
Female	127 32.1%	123 31.1%	250 31.6%
Male	269 67.9%	273 68.9%	542 68.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	59 14.9%	42 10.6%	101 12.8%
Not Hispanic or Latino	297 75%	307 77.5%	604 76.3%
Unknown or Not Reported	40 10.1%	47 11.9%	87 11%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.3%	1 0.1%
Asian	102 25.8%	114 28.8%	216 27.3%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.1%
Black or African American	5 1.3%	1 0.3%	6 0.8%
White	273 68.9%	262 66.2%	535 67.6%
Not collected at the site	14 3.5%	14 3.5%	28 3.5%
Other	1 0.3%	4 1%	5 0.6%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS)
Description	The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Time from date of randomization up to 1420 days

Outcome Measure Data

Analysis Population Description

PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with greater than or equal to (>=) 1 percentage (%) of tumor cells with >=1+ positive membrane staining intensity for PD-L1 protein.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	264	265
Median (95% Confidence Interval) [months]	11.4	10.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Docetaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.0721
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS) Time in Full Analysis Set Population
Description	The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Time from date of randomization up to 1420 days

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who were randomized to study.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	396	396
Median (95% Confidence Interval) [months]	10.6	9.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Docetaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population
Description	PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Time from date of randomization up to 907 days

Outcome Measure Data

Analysis Population Description

PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with >= 1 percentage of tumor cells with >=1+ positive membrane staining intensity for PD-L1 protein.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	264	265
Median (95% Confidence Interval) [months]	3.4	4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Docetaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Progression-Free Survival (PFS) Time in Full Analysis Set Population
Description	PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Time from date of randomization up to 907 days

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who were randomized to study.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	396	396
Median (95% Confidence Interval) [months]	2.8	4.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Docetaxel
	Comments
	Type of Statistical Test	Superiority
	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%; 0.98 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population
Description	Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Time Frame	Time from date of randomization up to 907 days

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who were randomized to study.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	396	396
Complete Response	5 1.3%	2 0.5%
Partial Response	54 13.6%	42 10.6%
Stable Disease	129 32.6%	158 39.9%
Non-complete Response/ Non-progressive Disease	5 1.3%	13 3.3%
Progressive Disease	150 37.9%	82 20.7%
Not Evaluable	53 13.4%	99 25%

6. Secondary Outcome

Title	Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population
Description	Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Time Frame	Time from date of randomization up to 907 days

Outcome Measure Data

Analysis Population Description

PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with >= 1 percentage of tumor cells with >=1+ positive membrane staining intensity for PD-L1 protein.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	264	265
Complete Response	4 1%	1 0.3%
Partial Response	46 11.6%	30 7.6%
Stable Disease	86 21.7%	104 26.3%
Non-complete Response/ Non-progressive Disease	4 1%	12 3%
Progressive Disease	93 23.5%	57 14.4%
Not Evaluable	31 7.8%	61 15.4%

7. Secondary Outcome

Title	Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population
Description	Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time Frame	Time from date of randomization up to 907 days

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who were randomized to study.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	396	396
Number (95% Confidence Interval) [percentage of participants]	14.9 3.8%	11.1 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Docetaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 0.92 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population
Description	Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time Frame	Time from date of randomization up to 907 days

Outcome Measure Data

Analysis Population Description

PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with >= 1 percentage of tumor cells with >=1+ positive membrane staining intensity for PD-L1 protein.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	264	265
Number (95% Confidence Interval) [percentage of participants]	18.9 4.8%	11.7 3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Docetaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.08 to 2.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)
Description	The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions).
Time Frame	Baseline, End of treatment visit (up to Week 124)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signified the participants analyzed in this outcome.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	172	196
Mean (Standard Deviation) [units on a scale]	-0.1245 (0.28021)	-0.0988 (0.26615)

10. Secondary Outcome

Title	Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)
Description	EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Time Frame	Baseline, End of treatment visit (up to Week 124)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signified the participants analyzed in this outcome.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	171	196
Mean (Standard Deviation) [millimeter]	-8.1 (22.06)	-7.0 (21.12)

11. Secondary Outcome

Title	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT)
Description	EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time Frame	Baseline, End of treatment visit (up to Week 124)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Overall Number of Participants Analyzed" signified the participants analyzed in this outcome.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	172	196
Mean (Standard Deviation) [units on a scale]	-9.79 (24.506)	-9.44 (18.933)

12. Secondary Outcome

Title	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT)
Description	EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).
Time Frame	Baseline, End of treatment visit (up to Week 124)

Outcome Measure Data

Analysis Population Description

Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, "Number Analyzed" signified those participants who were evaluable for the specified category.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	348	333
Dyspnea	9.95 (22.094)	8.52 (21.285)
Coughing	-0.58 (30.263)	-2.03 (32.582)
Hemoptysis	0.19 (14.191)	-0.34 (16.832)
Sore Mouth	0.78 (17.643)	3.72 (24.920)
Dysphagia	5.62 (18.401)	4.23 (21.538)
Peripheral Neuropathy	0.19 (20.550)	9.81 (30.015)
Alopecia	-3.10 (20.789)	30.80 (42.582)
Pain in Chest	4.84 (28.993)	0.34 (26.935)
Pain in Arm or Shoulder	5.62 (28.852)	0.85 (29.439)
Pain in Other Parts	8.77 (34.410)	6.60 (30.978)

13. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death
Description	An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time Frame	Time from date of randomization up to 1420 days

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	393	365
TEAEs	375 94.7%	346 87.4%
TESAEs	167 42.2%	145 36.6%
Drug Related TEAEs	252 63.6%	313 79%
TEAEs Leading to Death	64 16.2%	51 12.9%

14. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Description	Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event.
Time Frame	Time from date of randomization up to 1420 days

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	393	365
Grade 3 or Higher	209 52.8%	247 62.4%
Grade 4 or Higher	87 22%	122 30.8%
Grade 5	63 15.9%	51 12.9%

15. Secondary Outcome

Title	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score
Description	ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination.
Time Frame	Time from date of randomization up to 1420 days

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.

Arm/Group Title	Avelumab	Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.	Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	393	365
Baseline score 0, worst post-baseline score 0	52 13.1%	55 13.9%
Baseline score 0, worst post-baseline score 1	67 16.9%	41 10.4%
Baseline score 0, worst post-baseline score 2	19 4.8%	12 3%
Baseline score 0, worst post-baseline score 3	5 1.3%	2 0.5%
Baseline score 0, worst post-baseline score 4	0 0%	1 0.3%
Baseline score 0, worst post-baseline score 5	1 0.3%	0 0%
Baseline score 0, worst post-baseline Missing	0 0%	6 1.5%
Baseline score 1, worst post-baseline score 0	6 1.5%	1 0.3%
Baseline score 1, worst post-baseline score 1	157 39.6%	172 43.4%
Baseline score 1, worst post-baseline score 2	47 11.9%	41 10.4%
Baseline score 1, worst post-baseline score 3	23 5.8%	8 2%
Baseline score 1, worst post-baseline score 4	3 0.8%	2 0.5%
Baseline score 1, worst post-baseline score 5	1 0.3%	1 0.3%
Baseline score 1, worst post-baseline Missing	12 3%	23 5.8%

16. Secondary Outcome

Title	Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab
Description	Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported.
Time Frame	Time from date of randomization up to 1420 days

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who were randomized to study. Here, "Overall Number of Participants Analyzed" signified participants with at least on valid ADA result at any time point.

Arm/Group Title	Avelumab
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Measure Participants	388
ADAs to Avelumab	58 14.6%
NAbs to Avelumab	14 3.5%

Adverse Events

Time Frame	Time from date of randomization up to 1420 days.
Adverse Event Reporting Description	Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
Arm/Group Title	Avelumab		Docetaxel
Arm/Group Description	Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.		Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
All Cause Mortality
	Avelumab		Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	316/393 (80.4%)		297/365 (81.4%)
Serious Adverse Events
	Avelumab		Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	167/393 (42.5%)		145/365 (39.7%)
Blood and lymphatic system disorders
Anaemia	4/393 (1%)		3/365 (0.8%)
Febrile bone marrow aplasia	0/393 (0%)		1/365 (0.3%)
Febrile neutropenia	0/393 (0%)		22/365 (6%)
Leukopenia	0/393 (0%)		3/365 (0.8%)
Neutropenia	0/393 (0%)		10/365 (2.7%)
Cardiac disorders
Atrial fibrillation	3/393 (0.8%)		0/365 (0%)
Pericardial effusion	3/393 (0.8%)		0/365 (0%)
Cardiac arrest	2/393 (0.5%)		1/365 (0.3%)
Acute coronary syndrome	1/393 (0.3%)		0/365 (0%)
Angina unstable	1/393 (0.3%)		0/365 (0%)
Autoimmune myocarditis	1/393 (0.3%)		0/365 (0%)
Cardiac failure	1/393 (0.3%)		0/365 (0%)
Cardiac failure acute	1/393 (0.3%)		0/365 (0%)
Cardiac tamponade	2/393 (0.5%)		0/365 (0%)
Cardiomyopathy	1/393 (0.3%)		0/365 (0%)
Myocardial infarction	1/393 (0.3%)		1/365 (0.3%)
Acute myocardial infarction	1/393 (0.3%)		1/365 (0.3%)
Arrhythmia supraventricular	0/393 (0%)		1/365 (0.3%)
Cardiac failure congestive	0/393 (0%)		1/365 (0.3%)
Cardiovascular insufficiency	0/393 (0%)		1/365 (0.3%)
Left ventricular dysfunction	1/393 (0.3%)		0/365 (0%)
Ear and labyrinth disorders
Vertigo	1/393 (0.3%)		0/365 (0%)
Endocrine disorders
Adrenal insufficiency	1/393 (0.3%)		1/365 (0.3%)
Autoimmune thyroiditis	1/393 (0.3%)		0/365 (0%)
Eye disorders
Vision blurred	1/393 (0.3%)		0/365 (0%)
Gastrointestinal disorders
Abdominal pain	3/393 (0.8%)		1/365 (0.3%)
Colitis	3/393 (0.8%)		0/365 (0%)
Ascites	1/393 (0.3%)		1/365 (0.3%)
Diarrhoea	1/393 (0.3%)		5/365 (1.4%)
Gastric haemorrhage	1/393 (0.3%)		0/365 (0%)
Gastritis erosive	1/393 (0.3%)		0/365 (0%)
Gastrointestinal pain	1/393 (0.3%)		0/365 (0%)
Ileus	1/393 (0.3%)		0/365 (0%)
Melaena	1/393 (0.3%)		0/365 (0%)
Subileus	1/393 (0.3%)		0/365 (0%)
Constipation	0/393 (0%)		1/365 (0.3%)
Dysphagia	0/393 (0%)		2/365 (0.5%)
Ileus paralytic	0/393 (0%)		1/365 (0.3%)
Intestinal perforation	0/393 (0%)		1/365 (0.3%)
Nausea	0/393 (0%)		2/365 (0.5%)
Vomiting	0/393 (0%)		1/365 (0.3%)
Colitis ulcerative	1/393 (0.3%)		0/365 (0%)
General disorders
Disease progression	41/393 (10.4%)		26/365 (7.1%)
Asthenia	6/393 (1.5%)		3/365 (0.8%)
Death	6/393 (1.5%)		4/365 (1.1%)
Pain	2/393 (0.5%)		1/365 (0.3%)
Chest pain	1/393 (0.3%)		0/365 (0%)
Chills	1/393 (0.3%)		0/365 (0%)
General physical health deterioration	1/393 (0.3%)		1/365 (0.3%)
Non-cardiac chest pain	1/393 (0.3%)		1/365 (0.3%)
Oedema peripheral	1/393 (0.3%)		1/365 (0.3%)
Fatigue	0/393 (0%)		3/365 (0.8%)
Malaise	0/393 (0%)		1/365 (0.3%)
Mucosal inflammation	0/393 (0%)		2/365 (0.5%)
Pyrexia	0/393 (0%)		2/365 (0.5%)
Sudden cardiac death	0/393 (0%)		1/365 (0.3%)
Hepatobiliary disorders
Cholangitis	1/393 (0.3%)		0/365 (0%)
Hepatic function abnormal	1/393 (0.3%)		0/365 (0%)
Cholelithiasis	1/393 (0.3%)		0/365 (0%)
Immune system disorders
Hypersensitivity	2/393 (0.5%)		0/365 (0%)
Infections and infestations
Pneumonia	9/393 (2.3%)		19/365 (5.2%)
Respiratory tract infection	4/393 (1%)		5/365 (1.4%)
Lung infection	3/393 (0.8%)		2/365 (0.5%)
Sepsis	2/393 (0.5%)		2/365 (0.5%)
Appendicitis	1/393 (0.3%)		0/365 (0%)
Encephalitis	1/393 (0.3%)		0/365 (0%)
Gastroenteritis	1/393 (0.3%)		0/365 (0%)
Infective exacerbation of chronic obstructive airways disease	1/393 (0.3%)		0/365 (0%)
Pleural infection	1/393 (0.3%)		0/365 (0%)
Pneumonia streptococcal	1/393 (0.3%)		0/365 (0%)
Postoperative wound infection	1/393 (0.3%)		0/365 (0%)
Bronchitis	0/393 (0%)		4/365 (1.1%)
Diabetic gangrene	0/393 (0%)		1/365 (0.3%)
Infection	0/393 (0%)		2/365 (0.5%)
Klebsiella infection	0/393 (0%)		1/365 (0.3%)
Lower respiratory tract infection	0/393 (0%)		4/365 (1.1%)
Meningitis	0/393 (0%)		1/365 (0.3%)
Neutropenic infection	0/393 (0%)		1/365 (0.3%)
Neutropenic sepsis	0/393 (0%)		2/365 (0.5%)
Peritonitis	0/393 (0%)		1/365 (0.3%)
Pneumocystis jirovecii pneumonia	0/393 (0%)		1/365 (0.3%)
Septic shock	0/393 (0%)		5/365 (1.4%)
Serratia infection	0/393 (0%)		1/365 (0.3%)
Soft tissue infection	0/393 (0%)		1/365 (0.3%)
Streptococcal infection	0/393 (0%)		1/365 (0.3%)
Upper respiratory tract infection	0/393 (0%)		2/365 (0.5%)
Urinary tract infection	0/393 (0%)		1/365 (0.3%)
Urosepsis	0/393 (0%)		1/365 (0.3%)
Injury, poisoning and procedural complications
Infusion related reaction	10/393 (2.5%)		0/365 (0%)
Femoral neck fracture	2/393 (0.5%)		0/365 (0%)
Brain contusion	1/393 (0.3%)		0/365 (0%)
Femur fracture	1/393 (0.3%)		0/365 (0%)
Post procedural haemorrhage	1/393 (0.3%)		0/365 (0%)
Lumbar vertebral fracture	0/393 (0%)		1/365 (0.3%)
Spinal compression fracture	0/393 (0%)		1/365 (0.3%)
Investigations
Gamma-glutamyltransferase increased	1/393 (0.3%)		0/365 (0%)
Neutrophil count decreased	0/393 (0%)		4/365 (1.1%)
Alanine aminotransferase increased	1/393 (0.3%)		0/365 (0%)
Aspartate aminotransferase increased	1/393 (0.3%)		0/365 (0%)
Blood creatine phosphokinase increased	1/393 (0.3%)		0/365 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	3/393 (0.8%)		1/365 (0.3%)
Hyperglycaemia	3/393 (0.8%)		0/365 (0%)
Hyperkalaemia	2/393 (0.5%)		0/365 (0%)
Decreased appetite	1/393 (0.3%)		1/365 (0.3%)
Hyponatraemia	1/393 (0.3%)		0/365 (0%)
Dehydration	0/393 (0%)		2/365 (0.5%)
Electrolyte imbalance	0/393 (0%)		1/365 (0.3%)
Hypokalaemia	0/393 (0%)		1/365 (0.3%)
Hypophagia	0/393 (0%)		1/365 (0.3%)
Musculoskeletal and connective tissue disorders
Back pain	2/393 (0.5%)		2/365 (0.5%)
Arthralgia	1/393 (0.3%)		1/365 (0.3%)
Intervertebral disc protrusion	1/393 (0.3%)		0/365 (0%)
Osteoporotic fracture	1/393 (0.3%)		0/365 (0%)
Pain in extremity	1/393 (0.3%)		1/365 (0.3%)
Bone pain	0/393 (0%)		2/365 (0.5%)
Pathological fracture	0/393 (0%)		1/365 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	5/393 (1.3%)		1/365 (0.3%)
Malignant pleural effusion	2/393 (0.5%)		0/365 (0%)
Metastases to bone	2/393 (0.5%)		0/365 (0%)
Colorectal cancer	1/393 (0.3%)		0/365 (0%)
Malignant neoplasm progression	1/393 (0.3%)		1/365 (0.3%)
Metastases to liver	1/393 (0.3%)		0/365 (0%)
Metastases to meninges	1/393 (0.3%)		0/365 (0%)
Metastatic neoplasm	1/393 (0.3%)		0/365 (0%)
Tumour pain	1/393 (0.3%)		0/365 (0%)
Nervous system disorders
Depressed level of consciousness	2/393 (0.5%)		0/365 (0%)
Balance disorder	1/393 (0.3%)		0/365 (0%)
Cerebrovascular accident	1/393 (0.3%)		0/365 (0%)
Hemiparesis	1/393 (0.3%)		0/365 (0%)
Hemiplegia	1/393 (0.3%)		0/365 (0%)
Neurotoxicity	1/393 (0.3%)		0/365 (0%)
Post herpetic neuralgia	1/393 (0.3%)		0/365 (0%)
Seizure	1/393 (0.3%)		0/365 (0%)
Syncope	1/393 (0.3%)		0/365 (0%)
Cerebral infarction	0/393 (0%)		1/365 (0.3%)
Haemorrhage intracranial	0/393 (0%)		1/365 (0.3%)
Loss of consciousness	0/393 (0%)		1/365 (0.3%)
Paraesthesia	0/393 (0%)		1/365 (0.3%)
Spinal cord compression	0/393 (0%)		1/365 (0.3%)
Thrombotic cerebral infarction	1/393 (0.3%)		0/365 (0%)
Psychiatric disorders
Confusional state	2/393 (0.5%)		1/365 (0.3%)
Agitation	1/393 (0.3%)		0/365 (0%)
Renal and urinary disorders
Acute kidney injury	3/393 (0.8%)		2/365 (0.5%)
Nephrolithiasis	1/393 (0.3%)		0/365 (0%)
Renal impairment	1/393 (0.3%)		1/365 (0.3%)
Renal failure	1/393 (0.3%)		0/365 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	11/393 (2.8%)		7/365 (1.9%)
Pleural effusion	10/393 (2.5%)		3/365 (0.8%)
Chronic obstructive pulmonary disease	6/393 (1.5%)		3/365 (0.8%)
Pneumonitis	5/393 (1.3%)		1/365 (0.3%)
Pulmonary embolism	4/393 (1%)		3/365 (0.8%)
Haemoptysis	3/393 (0.8%)		4/365 (1.1%)
Interstitial lung disease	3/393 (0.8%)		3/365 (0.8%)
Respiratory failure	3/393 (0.8%)		3/365 (0.8%)
Acute respiratory failure	2/393 (0.5%)		2/365 (0.5%)
Hypoxia	2/393 (0.5%)		1/365 (0.3%)
Acute respiratory distress syndrome	1/393 (0.3%)		1/365 (0.3%)
Asphyxia	1/393 (0.3%)		0/365 (0%)
Atelectasis	1/393 (0.3%)		0/365 (0%)
Hydrothorax	1/393 (0.3%)		0/365 (0%)
Oesophagobronchial fistula	1/393 (0.3%)		0/365 (0%)
Pneumothorax	1/393 (0.3%)		1/365 (0.3%)
Pulmonary haemorrhage	1/393 (0.3%)		0/365 (0%)
Bronchial obstruction	0/393 (0%)		2/365 (0.5%)
Dysphonia	0/393 (0%)		1/365 (0.3%)
Dyspnoea exertional	0/393 (0%)		1/365 (0.3%)
Pneumonia aspiration	1/393 (0.3%)		1/365 (0.3%)
Cystic lung disease	1/393 (0.3%)		0/365 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/393 (0.3%)		0/365 (0%)
Henoch-Schonlein purpura	1/393 (0.3%)		0/365 (0%)
Rash maculo-papular	0/393 (0%)		1/365 (0.3%)
Vascular disorders
Superior vena cava syndrome	2/393 (0.5%)		1/365 (0.3%)
Aortic aneurysm	1/393 (0.3%)		0/365 (0%)
Intermittent claudication	1/393 (0.3%)		0/365 (0%)
Peripheral arterial occlusive disease	1/393 (0.3%)		0/365 (0%)
Deep vein thrombosis	0/393 (0%)		1/365 (0.3%)
Hypotension	0/393 (0%)		2/365 (0.5%)
Other (Not Including Serious) Adverse Events
	Avelumab		Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	320/393 (81.4%)		307/365 (84.1%)
Blood and lymphatic system disorders
Anaemia	50/393 (12.7%)		81/365 (22.2%)
Neutropenia	2/393 (0.5%)		48/365 (13.2%)
Endocrine disorders
Hypothyroidism	24/393 (6.1%)		1/365 (0.3%)
Gastrointestinal disorders
Nausea	56/393 (14.2%)		57/365 (15.6%)
Constipation	45/393 (11.5%)		43/365 (11.8%)
Diarrhoea	44/393 (11.2%)		67/365 (18.4%)
Vomiting	38/393 (9.7%)		28/365 (7.7%)
Stomatitis	9/393 (2.3%)		42/365 (11.5%)
General disorders
Fatigue	70/393 (17.8%)		66/365 (18.1%)
Asthenia	55/393 (14%)		64/365 (17.5%)
Pyrexia	50/393 (12.7%)		33/365 (9%)
Chills	29/393 (7.4%)		3/365 (0.8%)
Oedema peripheral	21/393 (5.3%)		37/365 (10.1%)
Malaise	9/393 (2.3%)		26/365 (7.1%)
Mucosal inflammation	5/393 (1.3%)		22/365 (6%)
Infections and infestations
Upper respiratory tract infection	28/393 (7.1%)		12/365 (3.3%)
Injury, poisoning and procedural complications
Infusion related reaction	56/393 (14.2%)		8/365 (2.2%)
Investigations
Weight decreased	50/393 (12.7%)		30/365 (8.2%)
Neutrophil count decreased	3/393 (0.8%)		34/365 (9.3%)
White blood cell count decreased	2/393 (0.5%)		21/365 (5.8%)
Metabolism and nutrition disorders
Decreased appetite	79/393 (20.1%)		76/365 (20.8%)
Musculoskeletal and connective tissue disorders
Back pain	47/393 (12%)		17/365 (4.7%)
Arthralgia	27/393 (6.9%)		30/365 (8.2%)
Musculoskeletal pain	25/393 (6.4%)		15/365 (4.1%)
Pain in extremity	23/393 (5.9%)		12/365 (3.3%)
Myalgia	17/393 (4.3%)		43/365 (11.8%)
Nervous system disorders
Headache	30/393 (7.6%)		19/365 (5.2%)
Neuropathy peripheral	6/393 (1.5%)		33/365 (9%)
Peripheral sensory neuropathy	3/393 (0.8%)		27/365 (7.4%)
Dysgeusia	1/393 (0.3%)		23/365 (6.3%)
Psychiatric disorders
Insomnia	19/393 (4.8%)		22/365 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	77/393 (19.6%)		46/365 (12.6%)
Dyspnoea	75/393 (19.1%)		54/365 (14.8%)
Productive cough	25/393 (6.4%)		8/365 (2.2%)
Haemoptysis	25/393 (6.4%)		15/365 (4.1%)
Skin and subcutaneous tissue disorders
Rash	33/393 (8.4%)		17/365 (4.7%)
Pruritus	26/393 (6.6%)		13/365 (3.6%)
Alopecia	3/393 (0.8%)		97/365 (26.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.