Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02952586
• Collaborator: (none)
• Enrollment: 697
• Locations: 316
• Arms: 2
• Actual Duration (Months): 44.9
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Avelumab; Other: Chemoradiation	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 697 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A RANDOMIZED DOUBLE-BLIND PHASE 3 STUDY OF AVELUMAB IN COMBINATION WITH STANDARD OF CARE CHEMORADIOTHERAPY (CISPLATIN PLUS DEFINITIVE RADIATION THERAPY) VERSUS STANDARD OF CARE CHEMORADIOTHERAPY IN THE FRONT-LINE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
• Actual Study Start Date: Nov 28, 2016
• Actual Primary Completion Date: Dec 23, 2019
• Actual Study Completion Date: Aug 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avelumab + SOC Chemoradiation Therapy Avelumab 10 mg/kg IV: Day 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; and Q2W for 12 months during the Maintenance Phase Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase Intensity Modulated Radiation Therapy (IMRT) 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase	Drug: Avelumab; Avelumab + SOC Chemoradiation
Placebo Comparator: Placebo + SOC CRT Placebo IV matching avelumab: Days 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; Q2W for 12 months during the Maintenance Phase Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase IMRT 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase	Other: Chemoradiation; Cisplatin + Radiation Therapy

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator [From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months)]

   PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event.

Secondary Outcome Measures

1. Overall Survival (OS) [From randomization to the date of death or censored date, whichever occurred first (up to 37 months)]

   Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method.

2. Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site [From randomization until PD or death (up to 37 months)]

   pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site.

3. Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator [From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months)]

   Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method.

4. Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator [From randomization until disease progression or death, whichever occurred first (up to 37 months)]

   Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than [<] 10 millimeter [mm]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (<10 mm short axis) . PR: Greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized.

5. Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator [From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months)]

   Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method.

6. Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator [From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months)]

   DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:>=30% decrease under baseline of sum of diameters of all target measurable lesions. CR for target disease:complete disappearance of all target lesions with exception of nodal disease.CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. PD is any of following:1)Locoregional PD confirmed by pathology to verify radiographic changes denote true tumor progression and not radiation effects or non-malignant contrast enhancement.2)Locoregional clinically detectable progression confirmed by pathology.3)Surgical removal of primary tumor with tumor present on final pathology.4)Salvage neck dissection >20 weeks after completion of CRT with tumor present on final pathology.5)Metastatic PD. DOR data was censored on date of last adequate tumor assessment for participants with no overall response.

7. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [Baseline up to 44 months]

   Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period.

8. Number of Participants With Shift From Baseline in Clinical Laboratory Parameters [Baseline up to 15 months]

   Grade 1 and 3 ranges are: Anemia:Hb:<LLN-10.0,<8.0 g/dL;LC decreased (dec):<LLN-800/mm^3,500-200/mm^3;LC increased (inc):grade 3:>20,000/mm^3:NC dec:<LLN-1500/mm^3;<1000-500/mm^3;PC dec:<LLN-75,000/mm^3;<50,000-25,000/mm^3;WBC dec:<LLN-3000/mm^3;<2000-1000/mm^3;ALT inc:>ULN-3.0*ULN;>5.0-20.0*ULN;ALP & GGT inc:>ULN-2.5*ULN;>5.0-20.0*ULN;AST inc:>ULN-3.0*ULN;>5.0-20.0*ULN;BB inc:>ULN-1.5*ULN;>3.0-10.0*ULN;CH high:>ULN-300 mg/dL;>400-500 mg/dL;CPK inc:>ULN-2.5*ULN;>5*ULN-10*ULN;Hypercalcemia:>ULN-11.5;>12.5-13.5mg/dL;Hyperglycemia:>ULN-160; >250-500mg/dL;Hyperkalemia:>ULN-5.5;>6.0-7.0mmol/L;Hypermagnesemia:>ULN-3.0;>3.0-8.0 mg/dL;Hypernatremia:>ULN-150; >155-160 mmol/L;Hypertriglyceridemia;150-300;>500-1000 mg/dL;Hypoalbuminemia:<LLN-3;<2g/dL;Hypocalcemia:<LLN-8.0;<8.0-7.0mg/dL;Hypokalemia:<LLN-3.0;<3.0-2.5mmol/L;Hypomagnesemia;<LLN-1.2;<0.9-0.7 mg/dL;Hyponatremia:<LLN-130;<130-120mmol/L; Hypophosphatemia:<LLN-2.5;<2.0-1.0mg/dL;lipase & serum amylase inc:>ULN-1.5*ULN;>2.0-5.0*ULN.

9. Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure [Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)]

   Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported.

10. Change From Baseline in Vital Sign - Pulse Rate [Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)]

    Change from baseline in pulse rate in sitting position in beats per minute was reported.

11. Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase [Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)]

    EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.

12. Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase [Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)]

    EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status.

13. Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase [Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)]

    The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning.

14. Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) [Baseline (prior to first dose)]

    PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells.

15. Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells [Baseline (prior to first dose)]

    Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm^2).

16. Percentage of Participants With Positive and Negative Pathology of Neck Dissection [From randomization until PD as per investigator assessment (up to 37 months)]

    Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study.

17. Maximum Plasma Concentration (Cmax) of Avelumab [Pre-dose and end of infusion on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1 and 2 (each cycle 28 days)]

    Maximum observed plasma concentration (Cmax) of Avelumab is reported.

18. Predose Plasma Concentration (Ctrough) of Avelumab [Pre-dose on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1, 2, 5, 8, 11 (each cycle 28 days)]

    Ctrough refers to plasma concentration of Avelumab observed just before treatment administration.

19. Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin [Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase]

    Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of total and free Cisplastin (in mg) administered to a participant.

20. Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin [Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase]

    Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). AUClast (dn) was calculated by dividing AUClast by the exact dose of cisplastin (in mg) administered to a participant.

21. Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin [Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase]

    Maximum observed plasma concentration (Cmax) of total and free Cisplatin is reported.

22. Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin [Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase]

    Time to reach maximum observed plasma concentration (Tmax) of total and free Cisplatin.

23. Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status [pre-dose on Day 1 up to 30 Days after the end of treatment]

    ADA never-positive was defined as no positive ADA results at any time point; ADA-negative participants (titer less than< cut point) and ADA ever-positive was defined as at least one positive ADA result at any time point; ADA-positive participants (titer greater than or equal to cut point)

24. Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status [Day 1 of lead-in phase and on Days 8 and 25 of CRT phase]

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA

• Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

• HPV negative disease, Stage III, IVa, IVb; non-oropharyngeal HPV positive disease Stage III, IVa, IVb, HPV positive oropharyngeal disease T4 or N2c or N3

• No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative intent.

• Available tumor samples for submission or willing to undergo further tumor biopsies:

• Age ≥18 years (≥19 in Korea;20 years in Japan and Taiwan).

• ECOG Performance Status 0 or 1

• Adequate bone marrow function

• Adequate renal function

• Adequate liver function

• Pregnancy test (for patients of childbearing potential) negative at screening

EXCLUSION CRITERIA

• Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways.

• Major surgery 4 weeks prior to randomization.

• Prior malignancy requiring tumor-directed therapy within the last 2 years prior to enrollment, or concurrent malignancy associated with clinical instability. Exceptions for disease within the 2 years are superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score 6) either curatively treated or deemed to not require treatment, ductal IS carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer.

• Active autoimmune disease

• Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.

• Active infection requiring systemic therapy.

• Use of immunosuppressive medication at time of randomization

• Prior organ transplantation including allogenic stem-cell transplantation.

• Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.

• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

• Vaccination within 4 weeks prior to randomization.

• Current use of or anticipated need for treatment with other anti-cancer drugs.

• Pregnant female patients, breastfeeding female patients, and male patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	Highlands Oncology Group	Rogers	Arkansas	United States	72758
3	Highlands Oncology Group	Springdale	Arkansas	United States	72762
4	The Oncology Institute of Hope and Innovation	Anaheim	California	United States	92801
5	CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
6	Beverly Hills Cancer Center	Beverly Hills	California	United States	90211
7	Tower Hematology Oncology Medical Group	Beverly Hills	California	United States	90211
8	UCSD Radiation Oncology South Bay, Cancer Treatment Centers	Chula Vista	California	United States	91914
9	City of Hope Corona	Corona	California	United States	92879
10	Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.	Corona	California	United States	92879
11	The Oncology Institute of Hope and Innovation	Downey	California	United States	90241
12	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California	United States	91010
13	The Oncology Institute of Hope and Innovation	Glendale	California	United States	91204
14	UC San Diego Medical Center- La Jolla (Thornton Hospital)	La Jolla	California	United States	92037
15	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
16	City of Hope Antelope Valley	Lancaster	California	United States	93534
17	The Oncology Institute of Hope and Innovation	Long Beach	California	United States	90805
18	The Oncology Institute of Hope and Innovation	Los Angeles	California	United States	90033
19	Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California	United States	90048
20	The Oncology Institute of Hope and Innovation	Lynwood	California	United States	90262
21	The Oncology Institute of Hope and Innovation	Montebello	California	United States	90640
22	UC Irvine Medical Center	Orange	California	United States	92868-3201
23	Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.	Riverside	California	United States	92501
24	UC San Diego Medical Center- Hillcrest	San Diego	California	United States	92103
25	The Oncology Institute of Hope and Innovation	Santa Ana	California	United States	92705
26	City of Hope South Pasadena	South Pasadena	California	United States	91030
27	The Oncology Institute of Hope and Innovation	Torrance	California	United States	90503
28	The Oncology Institute of Hope and Innovation	West Covina	California	United States	91790
29	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90602
30	Rocky Mountain Lions Eye Institute	Aurora	Colorado	United States	80045
31	University of Colorado Denver CTO/CTRC	Aurora	Colorado	United States	80045
32	University of Colorado Hospital - Anschutz Inpatient Pavilion	Aurora	Colorado	United States	80045
33	University of Colorado Hospital - Anschutz Outpatient Pavilion	Aurora	Colorado	United States	80045
34	University Of Colorado Hospital Cancer Center	Aurora	Colorado	United States	80045
35	Cypress Hematology & Oncology	Denver	Colorado	United States	80210
36	Cypress Hematology and Oncology	Parker	Colorado	United States	80138
37	Sylvester at Coral Gables	Coral Gables	Florida	United States	33146
38	Sylvester at Deerfield Beach	Deerfield Beach	Florida	United States	33442
39	Specialist Global LLC	Hialeah	Florida	United States	33012
40	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
41	Hollis Cancer Center	Lakeland	Florida	United States	33805
42	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
43	Memorial Cancer Institute at Memorial Hospital West	Pembroke Pines	Florida	United States	33028
44	Sylvester at Plantation	Plantation	Florida	United States	33324
45	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
46	Primary Healthcare Associates	Flossmoor	Illinois	United States	60422
47	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
48	Primary Healthcare Associates	Harvey	Illinois	United States	60426
49	Primary Healthcare Associates	Tinley Park	Illinois	United States	60477
50	IU Health Arnett Cancer Center	Lafayette	Indiana	United States	47904
51	Kansas City VA Radiation Oncology Clinic	Overland Park	Kansas	United States	66212
52	Ashland-Bellefonte Cancer Center	Ashland	Kentucky	United States	41101
53	Norton Cancer Institute	Louisville	Kentucky	United States	40202
54	Norton Hospital	Louisville	Kentucky	United States	40202
55	University Medical Center, Inc.	Louisville	Kentucky	United States	40202
56	Norton Brownsboro Hospital	Louisville	Kentucky	United States	40241
57	Norton Cancer Institute	Louisville	Kentucky	United States	40241
58	Highlands Cancer Center	Prestonsburg	Kentucky	United States	41653
59	Maryland Proton Treatment Center	Baltimore	Maryland	United States	21201
60	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
61	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
62	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
63	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
64	Henry Ford Hospital	Detroit	Michigan	United States	48202
65	Karmanos Cancer Institute	Farmington Hills	Michigan	United States	48334
66	Herbert-Herman Cancer Center, Sparrow Hospital	Lansing	Michigan	United States	48912
67	University of Missouri- Ellis Fischel Cancer Center	Columbia	Missouri	United States	65212
68	Siteman Cancer Center - West County	Creve Coeur	Missouri	United States	63141
69	Kansas City VA Medical Center	Kansas City	Missouri	United States	64128
70	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
71	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri	United States	63110
72	Siteman Cancer Center - South County	Saint Louis	Missouri	United States	63129
73	Siteman Cancer Center- St. Peters	Saint Peters	Missouri	United States	63376
74	Department of Radiation Oncology Methodist Hospital	Omaha	Nebraska	United States	68114
75	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68114
76	Memorial Sloan Kettering Cancer Center-Basking Ridge	Basking Ridge	New Jersey	United States	07920
77	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
78	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
79	Memorial Sloan Kettering Cancer Center- Monmouth	Middletown	New Jersey	United States	07748
80	Memorial Sloan Kettering Cancer Center- Bergen	Montvale	New Jersey	United States	07645
81	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico	United States	87131
82	Montefiore-Einstein Center for Cancer Care	Bronx	New York	United States	10461
83	Montefiore Medical Center	Bronx	New York	United States	10467
84	Memorial Sloan Kettering Cancer Center Commack	Commack	New York	United States	11725
85	Memorial Sloan Kettering Cancer Center Westchester	Harrison	New York	United States	10604
86	Bellevue Hospital Center	New York	New York	United States	10016
87	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
88	NYU Langone Medical Center	New York	New York	United States	10016
89	NYU Langone Radiology	New York	New York	United States	10016
90	NYU Langone Radiology - Ambulatory Care Center East 41st Street	New York	New York	United States	10017
91	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10022
92	Memorial Sloan Kettering Cancer Center: Breast and Imaging Center	New York	New York	United States	10065
93	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
94	Stony Brook University	Stony Brook	New York	United States	11794-7007
95	Stony Brook Cancer Center	Stony Brook	New York	United States	11794
96	Memorial Sloan Kettering Cancer Center- Nassau	Uniondale	New York	United States	11553
97	Oncology Specialists of Charlotte, PA	Charlotte	North Carolina	United States	28204
98	DJL Clinical Research, PLLC	Charlotte	North Carolina	United States	28210
99	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
100	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
101	OU Medical Center	Oklahoma City	Oklahoma	United States	73104
102	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
103	University of Oklahoma Health Sciences Center- Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
104	Lehigh Valley Health Network Cancer Center Pharmacy	Allentown	Pennsylvania	United States	18103
105	Lehigh Valley Health Network-Cedar Crest	Allentown	Pennsylvania	United States	18103
106	Radiation Oncology Cancer Services	Allentown	Pennsylvania	United States	18103
107	Lehigh Valley Health Network-Muhlenberg	Bethlehem	Pennsylvania	United States	18017
108	Precision Cancer Research / Gettysburg Cancer Center	Gettysburg	Pennsylvania	United States	17325
109	PinnacleHealth Cancer Institute	Harrisburg	Pennsylvania	United States	17109
110	PinnacleHealth Cancer Institute	Mechancisburg	Pennsylvania	United States	17050
111	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
112	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
113	UPMC Shadyside Radiation Oncology	Pittsburgh	Pennsylvania	United States	15232
114	MUSC- Rutledge Tower	Charleston	South Carolina	United States	29403
115	Medical University of South Carolina- Hollings Cancer Center	Charleston	South Carolina	United States	29425
116	MUSC SCTR Research Nexus Clinical Science Building	Charleston	South Carolina	United States	29425
117	MUSC- Ashley River Tower	Charleston	South Carolina	United States	29425
118	MUSC- Radiation Oncology	Charleston	South Carolina	United States	29425
119	MUSC- University Hospital	Charleston	South Carolina	United States	29425
120	GHS Cancer Institute	Easley	South Carolina	United States	29640
121	GHS Cancer Institute	Greenville	South Carolina	United States	29605
122	GHS Cancer Institute	Greenville	South Carolina	United States	29615
123	GHS Cancer Institute	Greer	South Carolina	United States	29650
124	GHS Cancer Institute	Seneca	South Carolina	United States	29672
125	GHS Cancer Institute	Spartanburg	South Carolina	United States	29307
126	The West Clinic, PC dba West Cancer Center	Germantown	Tennessee	United States	38138
127	The West Clinic PC dba West Cancer Center	Memphis	Tennessee	United States	38104
128	Henry-Joyce Cancer Clinic	Nashville	Tennessee	United States	37232
129	Texas Oncology El Paso Cancer Treatment Center	El Paso	Texas	United States	79902
130	William Beaumont Army Medical Center	El Paso	Texas	United States	79920-5001
131	William Beaumont Army Medical Center	El Paso	Texas	United States	79920
132	University of Texas Medical Branch	Galveston	Texas	United States	77555
133	Memorial Hermann Hospital - TMC	Houston	Texas	United States	77030
134	UTHealth/Memorial Hermann Cancer Center	Houston	Texas	United States	77030
135	UTMB Cancer Center at Victory Lakes	League City	Texas	United States	77573
136	Utah Cancer Specialists	Murray	Utah	United States	84157
137	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
138	Virginia Mason Medical Center	Seattle	Washington	United States	98101
139	VA Puget Sound Health Care System	Seattle	Washington	United States	98108
140	Chris O'Brien Lifehouse Medical Imaging	Camperdown	New South Wales	Australia	2050
141	Chris O'Brien Lifehouse Radiation Oncology Department	Camperdown	New South Wales	Australia	2050
142	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
143	Northern Sydney Cancer Centre	St Leonards	New South Wales	Australia	2065
144	Illawarra Shoalhaven Local Health District	Wollongong	New South Wales	Australia	2500
145	Barwon Health, University Hospital Geelong	Geelong	Victoria	Australia	3220
146	Austin Health	Heidelberg	Victoria	Australia	3084
147	Ordensklinikum Linz GmbH	Linz		Austria	A-4010
148	University Hospital Brussels	Brussels		Belgium	1090
149	Grand Hopital de Charleroi - Site Notre-Dame	Charleroi		Belgium	6000
150	Centre Hospitalier de Jolimont	Haine Saint Paul		Belgium	7100
151	Site Sainte Elisabeth / CHU UCL Namur	Namur		Belgium	5000
152	GZA Hospitals Campus Sint Augustinus	Wilrijk		Belgium	2610
153	CHU de Quebec - Universite Laval	Quebec		Canada	G1R 2J6
154	Beijing Cancer Hospital	Beijing	Beijing	China	100142
155	Fujian Cancer Hospital	Fuzhou	Fujian	China	350014
156	SUN Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510060
157	Cancer Center of Guangzhou Medical University/Oncology Department	Guangzhou	Guangdong	China	510095
158	Affiliated Tumor Hospital of Guangxi Medical University	Nanning	Guangxi	China	530021
159	Hai Nan General Hospital	Haikou	Hainan	China	570311
160	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150081
161	Henan Cancer Hospital	Zhengzhou	Henan	China	450008
162	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China	430022
163	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center	Wuhan	Hubei	China	430030
164	Xiangya Hospital Central South University/Oncology Department	Changsha	Hunan	China	410008
165	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning	China	110042
166	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
167	Shanghai East Hospital/Oncology Department	Shanghai	Shanghai	China	200123
168	West China Hospital of Sichuan University	Chengdu	Sichuan	China	610041
169	Tianjin Cancer Hospital	Tianjin	Tianjin	China	300060
170	Institut de Cancerologie de l'Ouest (ICO) - Site Paul Papin	Angers cedex 02		France	49055
171	Institut Sainte Catherine	Avignon cedex 9		France	84918
172	Hopital Pellegrin - Service de radiologie et d'imagerie	Bordeaux		France	33075
173	Hopital Saint-Andre	Bordeaux		France	33075
174	Cabinet de radiologie Privé - Dr Joseph Mocaer	Brest		France	29220
175	Clinique Pasteur - CFRO	Brest		France	29229
176	Hopital Franco-Britannique, Institut d'Oncologie Hauts-de-Seine Nord	Levallois-Perret		France	92309
177	Institut Regional du Cancer Montpellier - Val d'Aurelle	Montpellier cedex 5		France	34298
178	Hopital prive du Confluent S.A.S.	Nantes cedex 2		France	44277
179	Hopital prive du Confluent S.A.S	Nantes cedex 2		France	44277
180	Clinique Hartmann	Neuilly sur Seine		France	92200
181	Hopital Americain de Paris	Neuilly Sur Seine		France	92200
182	Centre Antoine Lacassagne	Nice cedex 2		France	06189
183	Institut Curie	Paris		France	75005
184	Centre Hospitalier Prive Saint Gregoire	Saint Gregoire		France	35760
185	Institut de Cancerologie de l'Ouest (ICO) - Site Rene Gauducheau	Saint Herblain Cedex		France	44805
186	Institut de cancerologie de la Loire Lucien Neuwirth	Saint Priest en Jarez cedex		France	42271
187	Centre Paul Strauss - Radiologie et medecine nucleaire	Strasbourg Cedex		France	67065
188	ICANS - Institut de cancerologie Strasbourg Europe	Strasbourg		France	67200
189	Institut Gustave Roussy	Villejuif		France	94800
190	Helios Klinikum Berlin-Buch, Institut fur Rontgendiagnostik	Berlin	Buch	Germany	13125
191	Helios Klinikum Berlin-Buch, Klinik fur Nuklearmedizin	Berlin	Buch	Germany	13125
192	Helios Klinikum Berlin-Buch, Klinik fur Strahlentherapie	Berlin	Buch	Germany	13125
193	Helios Klinikum Berlin-Buch	Berlin	Buch	Germany	13125
194	Universitatsklinikum Dusseldorf	Dusseldorf		Germany	40225
195	Universitatsklinikum Jena	Jena		Germany	07745
196	Universitatsklinikum Jena	Jena		Germany	07747
197	Universitätsklinikum Regensburg	Regensburg		Germany	93042
198	General Oncology Hospital of Kifissia "Agioi Anargiroi"	Athens	Attica	Greece	14564
199	Attikon University Hospital	Haidari	Attica	Greece	12462
200	Euromedica General Clinic	Thessaloniki		Greece	54645
201	Orszagos Onkologiai Intezet, B Belgyogyaszati Osztaly	Budapest		Hungary	1122
202	Orszagos Onkologiai Intezet, Sugarterapias Osztaly	Budapest		Hungary	1122
203	Uzsoki Utcai Korhaz	Budapest		Hungary	1145
204	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
205	Petz Aladar Megyei Oktato Koraz, Onkoradiologiai osztaly	Gyor		Hungary	9024
206	Pecsi Tudomanyegyetem, Klinikai Kozpont, Onkoterapias Intezet	Pecs		Hungary	7624
207	Szegedi Tudomanyegyetem, Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary	6720
208	St Luke's Radiation Oncology Network, St Luke's Hospital	Dublin		Ireland	6
209	St James's Hospital	Dublin		Ireland	8
210	St. James's Hospital	Dublin		Ireland	8
211	Blackrock Clinic	Dublin		Ireland	A94 E4X7
212	Rambam Health Care Campus	Haifa		Israel	3109601
213	Hadassah University Hospital, Department of Oncology	Jerusalem		Israel	91120
214	Rabin Medical Center	Petah Tiqva		Israel	4941492
215	The Chaim Sheba M.C.Tel-Hashomer	Ramat Gan		Israel	52621
216	ASST degli Spedali Civili di Brescia	Brescia	BS	Italy	25123
217	Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori (I.R.S.T)	Meldola	FC	Italy	47014
218	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola	FC	Italy	47014
219	Ospedale M. Bufalini	Cesena	Forlì-cesena	Italy	47521
220	IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola	Forlì-cesena	Italy	47014
221	Presidio Ospedaliero Vito Fazzi	Lecce	LE	Italy	73100
222	AOU Policlinico Di Modena	Modena	MO	Italy	41124
223	Azienda Ospedaliero-Universitaria di Parma	Parma	PR	Italy	43126
224	UOC Oncologia Medica, AUSL della Romagna -RAVENNA	Lugo	RA	Italy	48022
225	IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Ravenna	RA	Italy	48121
226	UOC Oncologia Medica, AUSL della Romagna - RAVENNA	Ravenna	RA	Italy	48121
227	AULSS 9 - Scaligera Ospedale Mater Salutis	Legnago	VR	Italy	37045
228	Istituto Nazionale Tumori IRCCS - Fondazione Pascale	Napoli		Italy	80131
229	AUSL - IRCCS and Reggio Emilia	Reggio Emilia		Italy	42123
230	Aichi cancer center central hospital	Nagoya	Aichi	Japan	464-8681
231	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
232	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
233	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime	Japan	791-0280
234	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
235	Kobe University Hospital	Kobe	Hyogo	Japan	650-0017
236	Miyagi Cancer Center	Natori	Miyagi	Japan	981-1293
237	Tohoku University Hospital	Sendai	Miyagi	Japan	980-8574
238	Osaka International Cancer Institute	Osaka-shi	Osaka	Japan	541-8567
239	Kindai University Hospital	Osakasayama	Osaka	Japan	589-8511
240	Saitama Cancer Center	Kita-adachi-gun	Saitama	Japan	362-0806
241	Shizuoka Cancer Center	Sunto-gun	Shizuoka	Japan	411-8777
242	Jichi Medical University Hospital	Shimotsuke	Tochigi	Japan	329-0498
243	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	1040045
244	Cancer Institute Hospital, Japanese Foundation for Cancer Research	Koto-ku	Tokyo	Japan	135-8550
245	Center for Proton Therapy, National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
246	Center for Specific Organ Cancer, National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
247	Department of Radiation Oncology, CHA Bundang Medical Center, CHA University	Seongnam-si	Gyeonggi-do	Korea, Republic of	13496
248	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
249	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do	Korea, Republic of	58128
250	Division of Radiation Oncology, Seoul National University Hospital	Seoul		Korea, Republic of	03080
251	Asan Medical Center	Seoul		Korea, Republic of	05505
252	Division of Radiation Oncology, Asan Medical Center	Seoul		Korea, Republic of	05505
253	Samsung Medical Center	Seoul		Korea, Republic of	06351
254	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
255	Department of Radiation Oncology, Ulsan University Hospital	Ulsan		Korea, Republic of	44033
256	Ulsan University Hospital	Ulsan		Korea, Republic of	44033
257	Centrum Onkologii im. prof. F. Lukaszczyka	Bydgoszcz		Poland	85-796
258	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
259	Centrum Onkologii - Instytut im. M. Sklodowskiej - Curie, Klinika Radioterapii i Chemioterapii	Gliwice		Poland	44-101
260	SPZOZ Ministerstwa Spraw Wewnetrznych i Administracji z Warminsko-Mazurskim Centrum Onkologii	Olsztyn		Poland	10-228
261	NZOZ Provita Prolife Centrum Medyczne	Tomaszow Mazowiecki		Poland	97-200
262	Specjalistyczny Szpital Onkologiczny NU-MED sp. z o.o.	Tomaszow Mazowiecki		Poland	97-200
263	Hospital Pedro Hispano	Matosinhos	Porto	Portugal	4464-513
264	CUF Porto	Senhora da Hora	Porto	Portugal	4460-188
265	Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE	Vila Nova de Gaia	Porto	Portugal	4434-502
266	Instituto Portugues de Oncologia de Coimbra Francisco Gentil, E.P.E.	Coimbra		Portugal	3000-075
267	Centro Hospitalar do Porto, E.P.E.- Hospital de Santo Antonio	Porto		Portugal	4099-001
268	Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.	Porto		Portugal	4200-072
269	Centro Hospitalar São João, E.P.E	Porto		Portugal	4200-319
270	Julio Teixeira	Porto		Portugal	4460-188
271	SBIH "Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine"	Chelyabinsk		Russian Federation	454087
272	N. N. Blokhin NMRCO	Moscow		Russian Federation	115478
273	Budgetary Institution of Healthcare of Omsk Region "Clinical Oncology Dispensary"	Omsk		Russian Federation	644013
274	FSBI "National Medical Research Center of Oncology n.a. N.N. Petrov"	Saint-Petersburg		Russian Federation	197758
275	SBIH "SPb Clinical Research Centre of Specialized Kinds of Medical Care (Oncology)"	Saint-Petersburg		Russian Federation	197758
276	SBHI YaR "Regional Clinical Oncology Hospital"	Yaroslavl		Russian Federation	150054
277	Institut Catala d'Oncologia Badalona, Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
278	Hospital Universitario Donostia	San Sebastian	Guipuzcoa	Spain	20014
279	Hospital Costa del Sol	Marbella	Malaga	Spain	29603
280	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
281	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
282	Hospital Clinic de Barcelona	Barcelona		Spain	08036
283	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
284	Hospital Universitario Reina Sofia	Cordoba		Spain	14004
285	Institut Catala D'Oncologia de Girona	Girona		Spain	17007
286	Complejo Hospitalario de Jaen	Jaen		Spain	23007
287	Hospital Clinico San Carlos	Madrid		Spain	28040
288	Hospital Universitario La Paz	Madrid		Spain	28046
289	Hospital Virgen de la Victoria	Malaga		Spain	29010
290	Hospital Universitario de Salamanca	Salamanca		Spain	37007
291	Fundacion Instituto Valenciano de Oncologia	Valencia		Spain	46009
292	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
293	Klinik fur Radiologie und Nuklearmedizin	Basel	Basel-stadt	Switzerland	4031
294	Klinik fur Strahlentherapie und Radioonkologie	Basel	Basel-stadt	Switzerland	4031
295	Universitatsspital Basel	Basel	Basel-stadt	Switzerland	4031
296	Istituto Oncologico della Svizzera Italiana IOSI, Ospedale San Giovanni	Bellinzona	Ticino	Switzerland	6500
297	Radiologia ORBV, Ospedale San Giovanni	Bellinzona	Ticino	Switzerland	6500
298	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud	Switzerland	1011
299	Kantonsspital Winterthur, Medizinische Onkologie	Winterthur	Zuerich	Switzerland	8401
300	Kantonsspital Winterthur, Radiologie	Winterthur	Zurich	Switzerland	8401
301	Kantonsspital Winterthur	Winterthur	Zurich	Switzerland	8401
302	Institut fur Klinische Pathologie	Zurich		Switzerland	8091
303	Klinik fur Nuklearmedizin	Zurich		Switzerland	8091
304	Universitatsspital Zurich	Zurich		Switzerland	8091
305	China Medical University Hospital	Taichung		Taiwan	40447
306	Taichung Veterans General Hospital	Taichung		Taiwan	40705
307	National Cheng Kung University Hospital	Tainan		Taiwan	704
308	National Taiwan University Hospital	Taipei		Taiwan	100
309	Taipei Veterans General Hospital	Taipei		Taiwan	11217
310	Koo Foundation Sun Yat-Sen Cancer Center	Taipei		Taiwan	112
311	Chang Gung Memorial Hospital-Linkou Branch	Taoyuan City		Taiwan	333
312	NHS Grampian	Aberdeen		United Kingdom	AB25 2ZN
313	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington		United Kingdom	CH63 4JY
314	University Hospital Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8ED
315	NHS Lothian, Western General Hospital	Edinburgh		United Kingdom	EH4 2XU
316	Guy's and St. Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Jul 31, 2019
• Statistical Analysis Plan - Aug 30, 2019

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02952586
• Other Study ID Numbers: B9991016; 2016-001456-21; LOCALLY ADVANCED HEAD AND NECK
• First Posted: Nov 2, 2016
• Last Update Posted: Sep 22, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Avelumab

Study Results

Participant Flow

Recruitment Details

Study had 3 sequential treatment phases: Lead-in, CRT, and Maintenance. There were 3 treatments administered in parallel during CRT phase: Avelumab, Cisplatin and IMRT.

Pre-assignment Detail

Study had 3 sequential treatment phases: Lead-in, CRT, and Maintenance. There were 3 treatments administered during CRT phase: Avelumab, Cisplatin and IMRT. Reasons for discontinuation of each treatment are summarized separately. 11 participants discontinued all 3 treatments during CRT phase due to death. Two patients discontinued cisplatin due to adverse event and subsequently discontinued avelumab and IMRT due to death.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Period Title: Lead-In Phase (7 Days)
STARTED	350	347
Safety Analysis Set	348	344
COMPLETED	345	343
NOT COMPLETED	5	4
Period Title: Lead-In Phase (7 Days)
STARTED	345	340
COMPLETED	312	313
NOT COMPLETED	33	27
Period Title: Lead-In Phase (7 Days)
STARTED	345	340
COMPLETED	234	236
NOT COMPLETED	111	104
Period Title: Lead-In Phase (7 Days)
STARTED	345	340
COMPLETED	322	320
NOT COMPLETED	23	20
Period Title: Lead-In Phase (7 Days)
STARTED	291	304
COMPLETED	139	177
NOT COMPLETED	152	127
Period Title: Lead-In Phase (7 Days)
STARTED	266	284
COMPLETED	208	216
NOT COMPLETED	58	68
Period Title: Lead-In Phase (7 Days)
STARTED	247	237
COMPLETED	0	0
NOT COMPLETED	247	237

Baseline Characteristics

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT	Total
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.	Total of all reporting groups
Overall Participants	350	347	697
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.36 (8.56)	58.88 (9.09)	59.12 (8.83)
Sex: Female, Male (Count of Participants)
Female	60 17.1%	62 17.9%	122 17.5%
Male	290 82.9%	285 82.1%	575 82.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 3.7%	8 2.3%	21 3%
Not Hispanic or Latino	312 89.1%	312 89.9%	624 89.5%
Unknown or Not Reported	25 7.1%	27 7.8%	52 7.5%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	9 2.6%	10 2.9%	19 2.7%
American Indian or Alaska Native	1 0.3%	0 0%	1 0.1%
Asian	102 29.1%	86 24.8%	188 27%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.3%	1 0.1%
White	224 64%	229 66%	453 65%
Other	14 4%	21 6.1%	35 5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator
Description	PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event.
Time Frame	From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	350	347
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9199
	Comments	The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor (T) stage (< T4 vs T4), Nodal (N) stage (N0 /N1/N2a/N2b vs N2c/N3), Human papillomavirus (HPV) status (Positive vs Negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.928 to 1.573
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method.
Time Frame	From randomization to the date of death or censored date, whichever occurred first (up to 37 months)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	350	347
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9372
	Comments	The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor (T) stage (< T4 vs T4), Nodal (N) stage (N0 /N1/N2a/N2b vs N2c/N3), Human papillomavirus (HPV) status (Positive vs Negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.927 to 1.849
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site
Description	pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site.
Time Frame	From randomization until PD or death (up to 37 months)

Outcome Measure Data

Analysis Population Description

All randomized participants who had salvage surgery at the primary site.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	6	7
Number (95% Confidence Interval) [percentage of participants]	0 0%	14.3 4.1%

4. Secondary Outcome

Title	Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator
Description	Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method.
Time Frame	From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	350	347
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9316
	Comments	The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor (T) stage (< T4 vs T4), Nodal (N) stage (N0 /N1/N2a/N2b vs N2c/N3), Human papillomavirus (HPV) status (Positive vs Negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.930 to 1.694
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator
Description	Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than [<] 10 millimeter [mm]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (<10 mm short axis) . PR: Greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized.
Time Frame	From randomization until disease progression or death, whichever occurred first (up to 37 months)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	350	347
Number (95% Confidence Interval) [percentage of participants]	74.0 21.1%	74.9 21.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6229
	Comments	The treatment arms were compared using a stratified, 1-sided, Cochran-Mantel-Haenszel Test. The 3 stratification factors were tumor stage (< T4 vs T4), Nodal stage (N0 /N1/N2a/N2b vs N2c/N3), HPV status (Positive vs Negative).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 95%; 0.663 to 1.352
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator
Description	Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method.
Time Frame	From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	350	347
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9061
	Comments	The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor stage (< T4 vs T4), Nodal stage (N0 /N1/N2a/N2b vs N2c/N3), HPV status (Positive vs Negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.909 to 1.624
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator
Description	DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:>=30% decrease under baseline of sum of diameters of all target measurable lesions. CR for target disease:complete disappearance of all target lesions with exception of nodal disease.CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. PD is any of following:1)Locoregional PD confirmed by pathology to verify radiographic changes denote true tumor progression and not radiation effects or non-malignant contrast enhancement.2)Locoregional clinically detectable progression confirmed by pathology.3)Surgical removal of primary tumor with tumor present on final pathology.4)Salvage neck dissection >20 weeks after completion of CRT with tumor present on final pathology.5)Metastatic PD. DOR data was censored on date of last adequate tumor assessment for participants with no overall response.
Time Frame	From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all randomized participants who had unconfirmed CR or PR.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	259	260
Median (95% Confidence Interval) [months]	NA	NA

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Description	Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period.
Time Frame	Baseline up to 44 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of study drug.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	348	344
Grade 1	10 2.9%	8 2.3%
Grade 2	30 8.6%	53 15.3%
Grade 3	224 64%	215 62%
Grade 4	59 16.9%	49 14.1%
Grade 5	22 6.3%	17 4.9%

9. Secondary Outcome

Title	Number of Participants With Shift From Baseline in Clinical Laboratory Parameters
Description	Grade 1 and 3 ranges are: Anemia:Hb:<LLN-10.0,<8.0 g/dL;LC decreased (dec):<LLN-800/mm^3,500-200/mm^3;LC increased (inc):grade 3:>20,000/mm^3:NC dec:<LLN-1500/mm^3;<1000-500/mm^3;PC dec:<LLN-75,000/mm^3;<50,000-25,000/mm^3;WBC dec:<LLN-3000/mm^3;<2000-1000/mm^3;ALT inc:>ULN-3.0*ULN;>5.0-20.0*ULN;ALP & GGT inc:>ULN-2.5*ULN;>5.0-20.0*ULN;AST inc:>ULN-3.0*ULN;>5.0-20.0*ULN;BB inc:>ULN-1.5*ULN;>3.0-10.0*ULN;CH high:>ULN-300 mg/dL;>400-500 mg/dL;CPK inc:>ULN-2.5*ULN;>5*ULN-10*ULN;Hypercalcemia:>ULN-11.5;>12.5-13.5mg/dL;Hyperglycemia:>ULN-160; >250-500mg/dL;Hyperkalemia:>ULN-5.5;>6.0-7.0mmol/L;Hypermagnesemia:>ULN-3.0;>3.0-8.0 mg/dL;Hypernatremia:>ULN-150; >155-160 mmol/L;Hypertriglyceridemia;150-300;>500-1000 mg/dL;Hypoalbuminemia:<LLN-3;<2g/dL;Hypocalcemia:<LLN-8.0;<8.0-7.0mg/dL;Hypokalemia:<LLN-3.0;<3.0-2.5mmol/L;Hypomagnesemia;<LLN-1.2;<0.9-0.7 mg/dL;Hyponatremia:<LLN-130;<130-120mmol/L; Hypophosphatemia:<LLN-2.5;<2.0-1.0mg/dL;lipase & serum amylase inc:>ULN-1.5*ULN;>2.0-5.0*ULN.
Time Frame	Baseline up to 15 months

Outcome Measure Data

Analysis Population Description

Safety population include all participants who received at least one dose of study drug. Here "Overall Number of Participants analyzed" signifies number of participants evaluable for this outcome measure and 'Number analyzed' signifies number of participants evaluable for specified rows.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	346	340
Anemia: New or worsened to grade >=1	314 89.7%	311 89.6%
Anemia: New or worsened to grade >=3	42 12%	49 14.1%
Lymphocyte Count Decreased: New or worsened to grade >=1	336 96%	330 95.1%
Lymphocyte Count (LC) Decreased: New or worsened to grade >=3	279 79.7%	284 81.8%
Lymphocyte Count (LC) Increased: New or worsened to grade >=1	7 2%	7 2%
Lymphocyte Count Increased: New or worsened to grade >=3	0 0%	0 0%
Neutrophil Count (NC) Decreased: New or worsened to grade >=1	257 73.4%	237 68.3%
Neutrophil Count Decreased: New or worsened to grade >=3	120 34.3%	101 29.1%
Platelet Count (PC) Decreased : New or worsened to grade >=1	157 44.9%	154 44.4%
Platelet Count Decreased: New or worsened to grade >=3	20 5.7%	7 2%
White Blood Cell (WBC) Decreased: New or worsened to grade >=1	309 88.3%	307 88.5%
White Blood Cell Decreased: New or worsened to grade >=3	121 34.6%	129 37.2%
Alanine aminotransferase (ALT) increased: New or worsened to grade >=1	152 43.4%	135 38.9%
ALT increased: New or worsened to grade >=3	13 3.7%	2 0.6%
Alkaline phosphatase increased (ALP): New or worsened to grade >=1	72 20.6%	49 14.1%
Alkaline phosphatase increased: New or worsened to grade >=3	1 0.3%	1 0.3%
Aspartate aminotransferase (AST) increased: New or worsened to grade >=1	146 41.7%	111 32%
Aspartate aminotransferase increased: New or worsened to grade >=3	11 3.1%	4 1.2%
Blood bilirubin (BB) increased (BB): New or worsened to grade >=1	58 16.6%	54 15.6%
Blood bilirubin increased: New or worsened to grade >=3	9 2.6%	4 1.2%
Cholesterol (CH) high: New or worsened to grade >=1	25 7.1%	21 6.1%
Cholesterol high: New or worsened to grade >=3	0 0%	0 0%
CPK increased: New or worsened to grade >=1	7 2%	7 2%
CPK increased: New or worsened to grade >=3	0 0%	1 0.3%
Creatinine increased: New or worsened to grade >=1	334 95.4%	325 93.7%
Creatinine increased: New or worsened to grade >=3	36 10.3%	37 10.7%
GGT increased: New or worsened to grade >=1	37 10.6%	23 6.6%
GGT increased: New or worsened to grade >=3	10 2.9%	5 1.4%
Hypercalcemia: New or worsened to grade >=1	67 19.1%	59 17%
Hypercalcemia: New or worsened to grade >=3	1 0.3%	5 1.4%
Hyperglycemia: New or worsened to grade >=1	144 41.1%	137 39.5%
Hyperglycemia: New or worsened to grade >=3	28 8%	29 8.4%
Hyperkalemia: New or worsened to grade >=1	106 30.3%	113 32.6%
Hyperkalemia: New or worsened to grade >=3	9 2.6%	17 4.9%
Hypermagnesemia: New or worsened to grade >=1	39 11.1%	40 11.5%
Hypermagnesemia: New or worsened to grade >=3	10 2.9%	10 2.9%
Hypernatremia: New or worsened to grade >=1	22 6.3%	20 5.8%
Hypernatremia: New or worsened to grade >=3	1 0.3%	0 0%
Hypertriglyceridemia: New or worsened to grade >=1	35 10%	26 7.5%
Hypertriglyceridemia: New or worsened to grade >=3	1 0.3%	2 0.6%
Hypoalbuminemia: New or worsened to grade >=1	195 55.7%	170 49%
Hypoalbuminemia: New or worsened to grade >=3	7 2%	5 1.4%
Hypocalcemia: New or worsened to grade >=1	82 23.4%	88 25.4%
Hypocalcemia: New or worsened to grade >=3	8 2.3%	14 4%
Hypoglycemia: New or worsened to grade >=1	56 16%	44 12.7%
Hypoglycemia: New or worsened to grade >=3	2 0.6%	2 0.6%
Hypokalemia: New or worsened to grade >=1	140 40%	122 35.2%
Hypokalemia: New or worsened to grade >=3	55 15.7%	49 14.1%
Hypomagnesemia: New or worsened to grade >=1	180 51.4%	158 45.5%
Hypomagnesemia: New or worsened to grade >=3	8 2.3%	12 3.5%
Hyponatremia: New or worsened to grade >=1	232 66.3%	212 61.1%
Hyponatremia: New or worsened to grade >=3	74 21.1%	70 20.2%
Hypophosphatemia: New or worsened to grade >=1	108 30.9%	100 28.8%
Hypophosphatemia: New or worsened to grade >=3	21 6%	19 5.5%
Lipase increased: New or worsened to grade >=1	19 5.4%	13 3.7%
Lipase increased: New or worsened to grade >=3	11 3.1%	3 0.9%
Serum amylase increased: New or worsened to grade >=1	13 3.7%	10 2.9%
Serum amylase increased: New or worsened to grade >=3	9 2.6%	5 1.4%

10. Secondary Outcome

Title	Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure
Description	Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported.
Time Frame	Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	342	336
DBP: Baseline	77.8 (10.13)	78.1 (10.91)
Lead in Phase: DBP: Change at Day 1	-3.0 (4.24)	-8.0 (11.31)
CRT Phase: DBP: Change at Day 1	-1.5 (9.52)	-2.2 (9.91)
CRT Phase: DBP: Change at Day 8	-3.8 (10.46)	-3.9 (10.99)
CRT Phase: DBP: Change at Day 22	-4.2 (11.77)	-5.0 (10.95)
CRT Phase: DBP: Change at Day 25	-3.4 (11.91)	-3.3 (11.44)
CRT Phase: DBP: Change at Day 39	-5.7 (11.83)	-5.1 (12.14)
CRT Phase: DBP: Change at Day 43	-5.0 (11.49)	-4.7 (11.76)
Maintenance Phase: DBP: Change at Cycle1/Day 1	-4.8 (11.43)	-4.3 (11.67)
Maintenance Phase: DBP: Change at Cycle1/Day 15	-3.7 (11.78)	-4.0 (10.96)
Maintenance Phase: DBP: Change at Cycle2/Day 1	-3.3 (11.74)	-3.3 (12.31)
Maintenance Phase: DBP: Change at Cycle2/Day 15	-2.7 (11.05)	-2.3 (11.82)
Maintenance Phase: DBP: Change at Cycle3/Day 1	-2.7 (11.37)	-3.6 (11.42)
Maintenance Phase: DBP: Change at Cycle3/Day 15	-2.7 (11.09)	-3.4 (11.10)
Maintenance Phase: DBP: Change at Cycle4/Day 1	-2.2 (12.07)	-3.4 (11.42)
Maintenance Phase: DBP: Change at Cycle4/Day 15	-2.4 (11.38)	-3.3 (11.54)
Maintenance Phase: DBP: Change at Cycle5/Day 1	-2.8 (11.61)	-3.2 (10.88)
Maintenance Phase: DBP: Change at Cycle5/Day 15	-2.5 (11.89)	-3.5 (10.69)
Maintenance Phase: DBP: Change at Cycle6/Day 1	-3.1 (11.21)	-3.8 (11.28)
Maintenance Phase: DBP: Change at Cycle6/Day 15	-3.8 (12.20)	-4.6 (11.43)
Maintenance Phase: DBP: Change at Cycle7/Day 1	-4.1 (11.48)	-4.2 (11.52)
Maintenance Phase: DBP: Change at Cycle7/Day 15	-3.8 (12.05)	-3.8 (10.88)
Maintenance Phase: DBP: Change at Cycle8/Day 1	-2.9 (11.29)	-4.1 (10.95)
Maintenance Phase: DBP: Change at Cycle8/Day 15	-3.4 (11.48)	-4.0 (12.29)
Maintenance Phase: DBP: Change at Cycle9/Day 1	-3.1 (11.78)	-4.2 (10.98)
Maintenance Phase: DBP: Change at Cycle9/Day 15	-2.1 (11.52)	-3.7 (12.07)
Maintenance Phase: DBP: Change at Cycle10/Day 1	-2.2 (11.58)	-3.5 (11.54)
Maintenance Phase: DBP: Change at Cycle10/Day 15	-2.5 (10.90)	-4.4 (11.69)
Maintenance Phase: DBP: Change at Cycle11/Day 1	-2.7 (11.01)	-4.6 (11.23)
Maintenance Phase: DBP: Change at Cycle11/Day 15	-2.9 (10.37)	-3.9 (10.22)
Maintenance Phase: DBP: Change at Cycle12/Day 1	-2.1 (9.51)	-3.5 (11.40)
Maintenance Phase: DBP: Change at Cycle12/Day 15	-3.3 (11.78)	-4.6 (11.19)
Maintenance Phase: DBP: Change at Cycle13/Day 1	-2.0 (9.60)	-3.3 (11.49)
Maintenance Phase: DBP: Change at Cycle13/Day 15	-1.1 (10.22)	-3.8 (11.44)
DBP: EOT	-2.4 (11.96)	-3.2 (11.17)
SBP: Baseline	129.8 (16.42)	130.5 (17.44)
Lead in Phase: SBP: Change at Day 1	-5.5 (2.12)	12.5 (6.36)
CRT Phase: SBP: Change at Day 1	-2.5 (15.32)	-3.5 (14.82)
CRT Phase: SBP: Change at Day 8	-8.3 (17.78)	-8.0 (17.58)
CRT Phase: SBP: Change at Day 22	-8.9 (18.54)	-8.4 (17.55)
CRT Phase: SBP: Change at Day 25	-7.9 (19.06)	-5.8 (19.51)
CRT Phase: SBP: Change at Day 39	-10.6 (20.51)	-10.3 (19.05)
CRT Phase: SBP: Change at Day 43	-9.6 (18.53)	-9.2 (19.52)
Maintenance Phase: SBP: Change at Cycle1/Day 1	-9.4 (17.97)	-9.4 (20.19)
Maintenance Phase: SBP: Change at Cycle1/Day 15	-9.5 (17.73)	-8.2 (19.58)
Maintenance Phase: SBP: Change at Cycle2/Day 1	-7.0 (18.03)	-7.8 (20.09)
Maintenance Phase: SBP: Change at /Cycle2/Day 15	-7.9 (18.55)	-6.6 (19.73)
Maintenance Phase: SBP: Change at Cycle3/Day 1	-7.3 (18.93)	-8.5 (18.04)
Maintenance Phase: SBP: Change at Cycle3/Day 15	-8.3 (17.79)	-7.1 (19.90)
Maintenance Phase: SBP: Change at Cycle4/Day 1	-8.4 (18.01)	-8.9 (18.41)
Maintenance Phase: SBP: Change at Cycle4/Day 15	-6.2 (18.20)	-8.2 (19.62)
Maintenance Phase: SBP: Change at Maintenance/Cycle5/Day 1	-7.6 (17.57)	-7.7 (18.69)
Maintenance Phase: SBP: Change at Cycle5/Day 15	-8.4 (18.69)	-7.5 (18.49)
Maintenance Phase: SBP: Change at Cycle6/Day 1	-7.6 (17.67)	-8.3 (18.96)
Maintenance Phase: SBP: Change at Cycle6/Day 15	-7.1 (19.35)	-9.4 (19.56)
Maintenance Phase: SBP: Change at Cycle7/Day 1	-9.0 (18.30)	-8.9 (18.96)
Maintenance Phase: SBP: Change at Cycle7/Day 15	-8.7 (18.10)	-6.8 (18.73)
Maintenance Phase: SBP: Change at Cycle8/Day 1	-6.5 (17.00)	-9.4 (18.65)
Maintenance Phase: SBP: Change at Cycle8/Day 15	-6.8 (16.69)	-7.9 (18.21)
Maintenance Phase: SBP: Change at Cycle9/Day 1	-6.1 (18.49)	-8.1 (18.41)
Maintenance Phase: SBP: Change at Cycle9/Day 15	-6.3 (19.00)	-6.7 (20.28)
Maintenance Phase: SBP: Change at Cycle10/Day 1	-6.1 (19.24)	-7.2 (18.63)
Maintenance Phase: SBP: Change at Cycle10/Day 15	-5.6 (17.07)	-7.7 (18.76)
Maintenance Phase: SBP: Change at Cycle11/Day 1	-6.3 (19.44)	-7.7 (18.86)
Maintenance Phase: SBP: Change at Cycle11/Day 15	-6.3 (18.99)	-7.4 (18.65)
Maintenance Phase: SBP: Change at Cycle12/Day 1	-6.8 (18.25)	-6.1 (20.21)
Maintenance Phase: SBP: Change at Cycle12/Day 15	-7.1 (19.34)	-7.8 (19.12)
Maintenance Phase: SBP: Change at Cycle13/Day 1	-5.8 (20.04)	-6.2 (18.54)
Maintenance Phase: SBP: Change at Cycle13/Day 15	-4.9 (18.82)	-5.6 (19.00)
SBP: EOT	-7.0 (19.83)	-4.9 (17.97)

11. Secondary Outcome

Title	Change From Baseline in Vital Sign - Pulse Rate
Description	Change from baseline in pulse rate in sitting position in beats per minute was reported.
Time Frame	Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	342	336
Baseline	79.9 (13.72)	86.0 (43.0)
Lead in Phase: Change at Day 1	-3.5 (0.71)	-8.5 (19.09)
CRT Phase: Change at Day 1	0.7 (11.70)	1.3 (10.92)
CRT Phase: Change at Day 8	1.5 (13.15)	2.2 (12.42)
CRT Phase: Change at Day 22	0.5 (13.86)	2.6 (12.24)
CRT Phase: Change at Day 25	-1.6 (14.87)	-1.2 (13.90)
CRT Phase: Change at Day 29	-11.0 (20.47)	3.6 (21.29)
CRT Phase: Change at Day 39	4.0 (15.46)	4.3 (14.71)
CRT Phase: Change at Day 43	4.7 (16.82)	6.1 (14.78)
Maintenance Phase: Change at Cycle1/Day 1	5.1 (16.23)	7.5 (14.43)
Maintenance Phase: Change at Cycle1/Day 15	3.8 (15.04)	6.3 (13.65)
Maintenance Phase: Change at Cycle2/Day 1	3.5 (15.30)	5.9 (14.74)
Maintenance Phase: Change at Cycle2/Day 15	4.1 (15.32)	4.9 (13.94)
Maintenance Phase: Change at Cycle3/Day 1	3.5 (14.49)	3.9 (14.37)
Maintenance Phase: Change at Cycle3/Day 15	2.8 (14.73)	2.8 (14.14)
Maintenance Phase: Change at Cycle4/Day 1	1.8 (14.79)	3.8 (14.95)
Maintenance Phase: Change at Cycle4/Day 15	1.6 (14.80)	3.8 (15.02)
Maintenance Phase: Change at Cycle5/Day 1	2.6 (13.88)	2.9 (14.82)
Maintenance Phase: Change at Cycle5/Day 15	1.6 (15.11)	3.3 (13.74)
Maintenance Phase: Change at Cycle6/Day 1	1.6 (15.42)	2.7 (15.72)
Maintenance Phase: Change at Cycle6/Day 15	0.4 (14.04)	1.4 (13.66)
Maintenance Phase: Change at Cycle7/Day 1	-0.1 (14.47)	2.5 (14.18)
Maintenance Phase: Change at Cycle7/Day 15	-0.1 (14.24)	1.4 (14.33)
Maintenance Phase: Change at Cycle8/Day 1	-0.2 (13.84)	1.0 (13.67)
Maintenance Phase: Change at Cycle8/Day 15	-1.5 (14.52)	1.5 (14.86)
Maintenance Phase: Change at Cycle9/Day 1	-1.0 (14.29)	-0.1 (14.06)
Maintenance Phase: Change at Cycle9/Day 15	-1.0 (14.20)	0.2 (14.44)
Maintenance Phase: Change at Cycle10/Day 1	-0.9 (13.40)	0.7 (14.52)
Maintenance Phase: Change at Cycle10/Day 15	-0.5 (15.33)	0.7 (14.66)
Maintenance Phase: Change at Cycle11/Day 1	-1.6 (14.57)	0.2 (14.01)
Maintenance Phase: Change at Cycle11/Day 15	-0.2 (13.23)	0.3 (12.93)
Maintenance Phase: Change at Cycle12/Day 1	-0.3 (13.92)	0.4 (13.67)
Maintenance Phase: Change at Cycle12/Day 15	-1.4 (14.92)	-0.5 (12.47)
Maintenance Phase: Change at Cycle13/Day 1	-1.4 (14.09)	-0.1 (12.22)
Maintenance Phase: Change at Cycle13/Day 15	-1.3 (15.57)	0.4 (13.24)
EOT	0.2 (14.73)	1.9 (14.09)

12. Secondary Outcome

Title	Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase
Description	EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Time Frame	Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	334	333
Baseline	0.7718 (0.17822)	0.7615 (0.18517)
CRT Phase: Change at Day 1	-0.0078 (0.13269)	0.0176 (0.14066)
CRT Phase: Change at Day 29	-0.0915 (0.22053)	-0.0487 (0.19175)
Maintenance Phase: Change at Cycle1/Day1	-0.0749 (0.22126)	-0.0519 (0.17253)
Maintenance Phase: Change at Cycle3/Day1	-0.0203 (0.21340)	-0.0160 (0.18179)
Maintenance Phase: Change at Cycle7/Day1	0.0088 (0.16690)	0.0140 (0.16240)
Maintenance Phase: Change at Cycle7/Day15	0.0552 (0.18544)	0.0472 (0.17990)
Maintenance Phase: Change at Cycle11/Day1	0.0376 (0.21078)	0.0792 (0.19287)
Maintenance Phase: Change at Cycle11/Day15	0.0673 (0.17227)	0.0389 (0.18732)
Maintenance Phase: Change at End of treatment	-0.0051 (0.24528)	0.0074 (0.24874)

13. Secondary Outcome

Title	Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase
Description	EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status.
Time Frame	Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants. FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	333	330
Baseline	75.8 (18.20)	74.9 (18.24)
CRT Phase: Change at Day 1	-1.1 (13.49)	-1.4 (11.39)
CRT Phase: Change at Day 29	-10.9 (19.94)	-9.2 (18.70)
Maintenance Phase: Change at Cycle1/Day1	-7.7 (19.05)	-6.2 (18.67)
Maintenance Phase: Change at Cycle3/Day1	-1.8 (18.00)	-0.7 (16.14)
Maintenance Phase: Change at Cycle7/Day1	-0.6 (14.91)	8.6 (81.42)
Maintenance Phase: Change at Cycle7/Day15	4.8 (18.52)	3.1 (19.28)
Maintenance Phase: Change at Cycle11/Day1	0.3 (17.60)	4.3 (16.10)
Maintenance Phase: Change at Cycle11/Day15	10.1 (24.69)	2.4 (18.20)
Maintenance Phase: Change at End of treatment	-1.9 (22.55)	0.7 (19.28)

14. Secondary Outcome

Title	Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase
Description	The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning.
Time Frame	Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	333	331
Baseline	60.56 (13.731)	61.05 (13.155)
CRT Phase: Change at Day 1	-0.59 (8.719)	-0.14 (9.136)
CRT Phase: Change at Day 29	-14.34 (16.847)	-14.56 (15.470)
CRT Phase: Change at Cycle1/Day1	-11.33 (16.054)	-12.08 (14.950)
CRT Phase: Change at Cycle3/Day1	-3.81 (14.017)	-2.26 (13.625)
CRT Phase: Change at Cycle7/Day1	-0.86 (12.503)	-0.51 (14.585)
CRT Phase: Change at Cycle7/Day15	3.96 (14.035)	0.92 (14.454)
CRT Phase: Change at Cycle11/Day1	2.68 (13.367)	4.90 (14.207)
CRT Phase: Change at Cycle11/Day15	3.96 (14.322)	3.37 (12.689)
CRT Phase: Change at End of treatment	-2.35 (17.428)	0.79 (16.509)

15. Secondary Outcome

Title	Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
Description	PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells.
Time Frame	Baseline (prior to first dose)

Outcome Measure Data

Analysis Population Description

Biomarker analysis set was a subset of the safety analysis set included participants who had at least one screening biomarker assessment. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	299	307
Positive Immune Cells	7.4 (7.06)	8.3 (8.47)
Tumor Staining Cells	12.7 (24.90)	18.3 (31.12)

16. Secondary Outcome

Title	Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells
Description	Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm^2).
Time Frame	Baseline (prior to first dose)

Outcome Measure Data

Analysis Population Description

Biomarker analysis set included all participants who had received at least one dose of study drug and who had at least one screening biomarker assessment. Here, 'Overall number of participants Analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	289	294
Mean (Standard Deviation) [% of tumor area occupied by CD8+ cells]	4.9 (6.03)	5.8 (6.55)

17. Secondary Outcome

Title	Percentage of Participants With Positive and Negative Pathology of Neck Dissection
Description	Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study.
Time Frame	From randomization until PD as per investigator assessment (up to 37 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who had received at least one dose of study drug and who had salvage neck dissection.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	14	15
Negative Pathology	7.14 2%	26.70 7.7%
Positive pathology	71.43 20.4%	40.00 11.5%
Pathology not reported	21.43 6.1%	33.30 9.6%

18. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Avelumab
Description	Maximum observed plasma concentration (Cmax) of Avelumab is reported.
Time Frame	Pre-dose and end of infusion on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1 and 2 (each cycle 28 days)

Outcome Measure Data

Analysis Population Description

PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'number analyzed' signifies participants evaluable at specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)
Arm/Group Description	Participants with LA SCCHN were administered with avelumab 10 mg/kg intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 mg/m^2 on Days 1, 22, 43 and IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	236
Lead-in/Day 1	203.6 (31)
CRT/Day 8	190.9 (66)
CRT/Day 25	162.4 (114)
Cycle 1 Day 1	142 (117)
Cycle 2 Day 1	154.9 (97)

19. Secondary Outcome

Title	Predose Plasma Concentration (Ctrough) of Avelumab
Description	Ctrough refers to plasma concentration of Avelumab observed just before treatment administration.
Time Frame	Pre-dose on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1, 2, 5, 8, 11 (each cycle 28 days)

Outcome Measure Data

Analysis Population Description

PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'number analyzed' signifies participants evaluable at specified time point.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	267
Lead-in/Day 1	2.988 (1590)
CRT/Day 8	11.9 (63)
CRT/Day 25	6.284 (138)
Cycle 1/Day 1	2.354 (131)
Cycle 2/Day 1	17.56 (70)
Cycle 5/Day 1	24.35 (66)
Cycle 8/Day 1	29.59 (69)
Cycle 11/Day 1	30.85 (79)

20. Secondary Outcome

Title	Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin
Description	Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of total and free Cisplastin (in mg) administered to a participant.
Time Frame	Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

Outcome Measure Data

Analysis Population Description

PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	12	23
Total Cisplastin	26.23 (36)	25.33 (26)
Free Cisplastin	11.84 (29)	7.286 (96)

21. Secondary Outcome

Title	Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin
Description	Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). AUClast (dn) was calculated by dividing AUClast by the exact dose of cisplastin (in mg) administered to a participant.
Time Frame	Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

Outcome Measure Data

Analysis Population Description

PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	10	20
Total Cisplatin	299.1 (30)	332.7 (17)
Free Cisplatin	36.53 (51)	29.08 (49)

22. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin
Description	Maximum observed plasma concentration (Cmax) of total and free Cisplatin is reported.
Time Frame	Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

Outcome Measure Data

Analysis Population Description

PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	12	23
Total Cisplatin	3781 (44)	4001 (34)
Free Cisplatin	1710 (53)	1151 (109)

23. Secondary Outcome

Title	Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin
Description	Time to reach maximum observed plasma concentration (Tmax) of total and free Cisplatin.
Time Frame	Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

Outcome Measure Data

Analysis Population Description

PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	12	23
Total Cisplatin	1.000	1.170
Free Cisplatin	1.000	1.000

24. Secondary Outcome

Title	Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
Description	ADA never-positive was defined as no positive ADA results at any time point; ADA-negative participants (titer less than< cut point) and ADA ever-positive was defined as at least one positive ADA result at any time point; ADA-positive participants (titer greater than or equal to cut point)
Time Frame	pre-dose on Day 1 up to 30 Days after the end of treatment

Outcome Measure Data

Analysis Population Description

Immunogenicity analysis set was a subset of the safety analysis set which included participants who had at least 1 ADA/nAb sample collected for avelumab in Avelumab + Standard of Care Chemotherapy (SOC CRT) arm.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	331
ADA never-positive	277 79.1%
ADA ever-positive	54 15.4%

25. Secondary Outcome

Title	Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status
Time Frame	Day 1 of lead-in phase and on Days 8 and 25 of CRT phase

Outcome Measure Data

Analysis Population Description

Since the study was terminated, sponsor decided not to collect data for nAb, hence not reported.

Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.	Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Measure Participants	0	0

Adverse Events

Time Frame	Baseline up to 44 months
Adverse Event Reporting Description	Same event may appear as AE, serious AE, here distinct events are presented. Event may be serious in 1 participant and non-serious in another or 1 participant may have experienced both serious, non-serious event. Safety analysis set evaluated. Discontinuation during CRT phase due to death is the discontinuation reason for treatments received at the time of event in the treatment disposition summary.All deaths reported as reason of discontinuation at any phase are included in all-cause mortality.
Arm/Group Title	Avelumab + Standard of Care Chemotherapy (SOC CRT)		Placebo + SOC CRT
Arm/Group Description	Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment.		Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
All Cause Mortality
	Avelumab + Standard of Care Chemotherapy (SOC CRT)		Placebo + SOC CRT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/348 (24.7%)		62/344 (18%)
Serious Adverse Events
	Avelumab + Standard of Care Chemotherapy (SOC CRT)		Placebo + SOC CRT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	184/348 (52.9%)		177/344 (51.5%)
Blood and lymphatic system disorders
Anaemia	8/348 (2.3%)		12/344 (3.5%)
Bone marrow failure	2/348 (0.6%)		1/344 (0.3%)
Febrile neutropenia	9/348 (2.6%)		5/344 (1.5%)
Leukopenia	1/348 (0.3%)		0/344 (0%)
Lymphadenopathy	0/348 (0%)		1/344 (0.3%)
Neutropenia	5/348 (1.4%)		3/344 (0.9%)
Splenic haematoma	1/348 (0.3%)		0/344 (0%)
Thrombocytopenia	1/348 (0.3%)		0/344 (0%)
Cardiac disorders
Acute coronary syndrome	1/348 (0.3%)		0/344 (0%)
Acute myocardial infarction	1/348 (0.3%)		1/344 (0.3%)
Angina pectoris	0/348 (0%)		1/344 (0.3%)
Atrial fibrillation	0/348 (0%)		1/344 (0.3%)
Bradycardia	1/348 (0.3%)		2/344 (0.6%)
Cardiac arrest	1/348 (0.3%)		0/344 (0%)
Cardiac failure	1/348 (0.3%)		2/344 (0.6%)
Cardiac failure congestive	1/348 (0.3%)		0/344 (0%)
Cardio-respiratory arrest	1/348 (0.3%)		0/344 (0%)
Sinus tachycardia	0/348 (0%)		1/344 (0.3%)
Supraventricular tachycardia	2/348 (0.6%)		0/344 (0%)
Tachycardia	0/348 (0%)		1/344 (0.3%)
Ear and labyrinth disorders
Deafness	1/348 (0.3%)		0/344 (0%)
Tinnitus	0/348 (0%)		1/344 (0.3%)
Vertigo	1/348 (0.3%)		0/344 (0%)
Endocrine disorders
Adrenal insufficiency	0/348 (0%)		1/344 (0.3%)
Hyperthyroidism	0/348 (0%)		1/344 (0.3%)
Eye disorders
Pterygium	0/348 (0%)		1/344 (0.3%)
Retinal detachment	0/348 (0%)		1/344 (0.3%)
Gastrointestinal disorders
Abdominal pain	0/348 (0%)		2/344 (0.6%)
Colitis	1/348 (0.3%)		2/344 (0.6%)
Constipation	1/348 (0.3%)		1/344 (0.3%)
Diarrhoea	1/348 (0.3%)		2/344 (0.6%)
Dry mouth	0/348 (0%)		1/344 (0.3%)
Duodenal ulcer perforation	1/348 (0.3%)		0/344 (0%)
Dyspepsia	1/348 (0.3%)		0/344 (0%)
Dysphagia	15/348 (4.3%)		13/344 (3.8%)
Faecaloma	0/348 (0%)		1/344 (0.3%)
Gastric perforation	1/348 (0.3%)		1/344 (0.3%)
Haematemesis	1/348 (0.3%)		1/344 (0.3%)
Haematochezia	1/348 (0.3%)		0/344 (0%)
Large intestinal obstruction	0/348 (0%)		1/344 (0.3%)
Mouth haemorrhage	2/348 (0.6%)		2/344 (0.6%)
Mouth swelling	0/348 (0%)		1/344 (0.3%)
Nausea	7/348 (2%)		9/344 (2.6%)
Odynophagia	3/348 (0.9%)		1/344 (0.3%)
Oesophageal obstruction	1/348 (0.3%)		0/344 (0%)
Oesophagitis	1/348 (0.3%)		1/344 (0.3%)
Oral pain	1/348 (0.3%)		2/344 (0.6%)
Pneumoperitoneum	1/348 (0.3%)		0/344 (0%)
Salivary hypersecretion	1/348 (0.3%)		0/344 (0%)
Stomatitis	7/348 (2%)		4/344 (1.2%)
Tongue haemorrhage	2/348 (0.6%)		0/344 (0%)
Tongue ulceration	1/348 (0.3%)		0/344 (0%)
Upper gastrointestinal haemorrhage	1/348 (0.3%)		0/344 (0%)
Vomiting	11/348 (3.2%)		13/344 (3.8%)
General disorders
Asthenia	2/348 (0.6%)		6/344 (1.7%)
Chest pain	2/348 (0.6%)		1/344 (0.3%)
Chills	2/348 (0.6%)		0/344 (0%)
Condition aggravated	1/348 (0.3%)		0/344 (0%)
Death	2/348 (0.6%)		1/344 (0.3%)
Disease progression	1/348 (0.3%)		1/344 (0.3%)
Fatigue	2/348 (0.6%)		2/344 (0.6%)
General physical health deterioration	1/348 (0.3%)		6/344 (1.7%)
Hyperpyrexia	1/348 (0.3%)		0/344 (0%)
Hyperthermia	0/348 (0%)		2/344 (0.6%)
Hypothermia	0/348 (0%)		1/344 (0.3%)
Ill-defined disorder	0/348 (0%)		1/344 (0.3%)
Malaise	0/348 (0%)		1/344 (0.3%)
Mucosal inflammation	5/348 (1.4%)		6/344 (1.7%)
Pain	0/348 (0%)		2/344 (0.6%)
Performance status decreased	0/348 (0%)		1/344 (0.3%)
Pyrexia	12/348 (3.4%)		3/344 (0.9%)
Sudden death	0/348 (0%)		1/344 (0.3%)
Swelling	1/348 (0.3%)		0/344 (0%)
Hepatobiliary disorders
Cholelithiasis	0/348 (0%)		1/344 (0.3%)
Hepatitis	1/348 (0.3%)		0/344 (0%)
Hepatotoxicity	1/348 (0.3%)		0/344 (0%)
Infections and infestations
Abdominal abscess	1/348 (0.3%)		0/344 (0%)
Abscess oral	0/348 (0%)		1/344 (0.3%)
Anal abscess	0/348 (0%)		1/344 (0.3%)
Appendicitis	0/348 (0%)		1/344 (0.3%)
Bacterial infection	0/348 (0%)		1/344 (0.3%)
Bronchitis	1/348 (0.3%)		1/344 (0.3%)
Bronchitis bacterial	1/348 (0.3%)		0/344 (0%)
Candida infection	1/348 (0.3%)		0/344 (0%)
Cellulitis	3/348 (0.9%)		2/344 (0.6%)
Device related infection	2/348 (0.6%)		1/344 (0.3%)
Device related sepsis	1/348 (0.3%)		0/344 (0%)
Endocarditis	0/348 (0%)		1/344 (0.3%)
Endocarditis candida	1/348 (0.3%)		0/344 (0%)
Enterocolitis infectious	2/348 (0.6%)		0/344 (0%)
Epididymitis	1/348 (0.3%)		0/344 (0%)
Epiglottitis	1/348 (0.3%)		0/344 (0%)
Herpes zoster	1/348 (0.3%)		0/344 (0%)
Infection	1/348 (0.3%)		3/344 (0.9%)
Infectious pleural effusion	0/348 (0%)		1/344 (0.3%)
Localised infection	1/348 (0.3%)		0/344 (0%)
Lower respiratory tract infection	2/348 (0.6%)		2/344 (0.6%)
Lower respiratory tract infection bacterial	0/348 (0%)		1/344 (0.3%)
Lung abscess	1/348 (0.3%)		0/344 (0%)
Neutropenic infection	1/348 (0.3%)		0/344 (0%)
Neutropenic sepsis	1/348 (0.3%)		0/344 (0%)
Oesophageal candidiasis	1/348 (0.3%)		0/344 (0%)
Oral candidiasis	0/348 (0%)		1/344 (0.3%)
Oral infection	0/348 (0%)		1/344 (0.3%)
Parotitis	2/348 (0.6%)		1/344 (0.3%)
Pharyngitis	0/348 (0%)		2/344 (0.6%)
Pneumococcal sepsis	1/348 (0.3%)		0/344 (0%)
Pneumonia	25/348 (7.2%)		20/344 (5.8%)
Pneumonia bacterial	2/348 (0.6%)		0/344 (0%)
Respiratory tract infection	4/348 (1.1%)		0/344 (0%)
Sepsis	7/348 (2%)		5/344 (1.5%)
Sinusitis	1/348 (0.3%)		0/344 (0%)
Skin infection	1/348 (0.3%)		0/344 (0%)
Soft tissue infection	1/348 (0.3%)		1/344 (0.3%)
Staphylococcal sepsis	1/348 (0.3%)		0/344 (0%)
Stoma site abscess	1/348 (0.3%)		0/344 (0%)
Stoma site infection	1/348 (0.3%)		1/344 (0.3%)
Urinary tract infection	2/348 (0.6%)		1/344 (0.3%)
Vascular device infection	1/348 (0.3%)		0/344 (0%)
Osteomyelitis	0/348 (0%)		1/344 (0.3%)
Injury, poisoning and procedural complications
Femoral neck fracture	1/348 (0.3%)		0/344 (0%)
Femur fracture	1/348 (0.3%)		0/344 (0%)
Gastrostomy failure	1/348 (0.3%)		0/344 (0%)
Infusion related reaction	2/348 (0.6%)		0/344 (0%)
Nerve injury	0/348 (0%)		1/344 (0.3%)
Overdose	1/348 (0.3%)		0/344 (0%)
Pancreatic injury	0/348 (0%)		1/344 (0.3%)
Post procedural fever	1/348 (0.3%)		0/344 (0%)
Post procedural haemorrhage	2/348 (0.6%)		1/344 (0.3%)
Radiation associated pain	0/348 (0%)		1/344 (0.3%)
Radiation fibrosis	1/348 (0.3%)		0/344 (0%)
Radiation injury	0/348 (0%)		1/344 (0.3%)
Radiation mucositis	0/348 (0%)		2/344 (0.6%)
Radiation necrosis	0/348 (0%)		1/344 (0.3%)
Radiation skin injury	3/348 (0.9%)		2/344 (0.6%)
Stoma site inflammation	0/348 (0%)		1/344 (0.3%)
Stoma site pain	0/348 (0%)		1/344 (0.3%)
Subdural haemorrhage	1/348 (0.3%)		0/344 (0%)
Thermal burn	0/348 (0%)		1/344 (0.3%)
Tracheal haemorrhage	2/348 (0.6%)		0/344 (0%)
Tracheal obstruction	1/348 (0.3%)		0/344 (0%)
Osteoradionecrosis	0/348 (0%)		1/344 (0.3%)
Investigations
Alanine aminotransferase increased	1/348 (0.3%)		0/344 (0%)
Blood creatinine increased	7/348 (2%)		6/344 (1.7%)
C-reactive protein increased	0/348 (0%)		1/344 (0.3%)
Eastern Cooperative Oncology Group performance status worsened	0/348 (0%)		1/344 (0.3%)
Hepatic enzyme increased	1/348 (0.3%)		0/344 (0%)
Liver function test abnormal	0/348 (0%)		1/344 (0.3%)
Liver function test increased	1/348 (0.3%)		0/344 (0%)
Lymphocyte count decreased	0/348 (0%)		1/344 (0.3%)
Neutrophil count decreased	4/348 (1.1%)		1/344 (0.3%)
Oxygen saturation decreased	1/348 (0.3%)		0/344 (0%)
Weight decreased	6/348 (1.7%)		3/344 (0.9%)
White blood cell count decreased	0/348 (0%)		1/344 (0.3%)
Metabolism and nutrition disorders
Adult failure to thrive	0/348 (0%)		1/344 (0.3%)
Cachexia	2/348 (0.6%)		2/344 (0.6%)
Decreased appetite	5/348 (1.4%)		3/344 (0.9%)
Dehydration	9/348 (2.6%)		15/344 (4.4%)
Diabetes mellitus inadequate control	1/348 (0.3%)		0/344 (0%)
Diabetic ketoacidosis	0/348 (0%)		1/344 (0.3%)
Electrolyte imbalance	1/348 (0.3%)		0/344 (0%)
Failure to thrive	2/348 (0.6%)		1/344 (0.3%)
Fluid overload	1/348 (0.3%)		0/344 (0%)
Hypercalcaemia	1/348 (0.3%)		1/344 (0.3%)
Hyperglycaemia	2/348 (0.6%)		0/344 (0%)
Hyperglycaemic hyperosmolar nonketotic syndrome	1/348 (0.3%)		0/344 (0%)
Hypoalbuminaemia	0/348 (0%)		1/344 (0.3%)
Hypocalcaemia	0/348 (0%)		2/344 (0.6%)
Hypoglycaemia	0/348 (0%)		1/344 (0.3%)
Hypokalaemia	4/348 (1.1%)		3/344 (0.9%)
Hyponatraemia	4/348 (1.1%)		7/344 (2%)
Hypophagia	1/348 (0.3%)		0/344 (0%)
Ketoacidosis	0/348 (0%)		1/344 (0.3%)
Malnutrition	2/348 (0.6%)		3/344 (0.9%)
Metabolic disorder	0/348 (0%)		1/344 (0.3%)
Musculoskeletal and connective tissue disorders
Arthritis	1/348 (0.3%)		0/344 (0%)
Back pain	0/348 (0%)		1/344 (0.3%)
Haematoma muscle	0/348 (0%)		1/344 (0.3%)
Neck pain	1/348 (0.3%)		1/344 (0.3%)
Oligoarthritis	1/348 (0.3%)		0/344 (0%)
Osteonecrosis of jaw	0/348 (0%)		1/344 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	0/348 (0%)		1/344 (0.3%)
Non-small cell lung cancer	1/348 (0.3%)		0/344 (0%)
Oesophageal carcinoma	0/348 (0%)		1/344 (0.3%)
Oesophageal neoplasm	1/348 (0.3%)		0/344 (0%)
Plasmacytoma	0/348 (0%)		1/344 (0.3%)
Transitional cell cancer of the renal pelvis and ureter	1/348 (0.3%)		0/344 (0%)
Tumour haemorrhage	4/348 (1.1%)		4/344 (1.2%)
Nervous system disorders
Brain hypoxia	1/348 (0.3%)		0/344 (0%)
Cerebral ischaemia	0/348 (0%)		1/344 (0.3%)
Cerebrovascular accident	1/348 (0.3%)		1/344 (0.3%)
Coma	1/348 (0.3%)		0/344 (0%)
Depressed level of consciousness	0/348 (0%)		1/344 (0.3%)
Dizziness	0/348 (0%)		1/344 (0.3%)
Epilepsy	1/348 (0.3%)		1/344 (0.3%)
Headache	1/348 (0.3%)		0/344 (0%)
Presyncope	0/348 (0%)		1/344 (0.3%)
Seizure	0/348 (0%)		1/344 (0.3%)
Subacute combined cord degeneration	0/348 (0%)		1/344 (0.3%)
Syncope	2/348 (0.6%)		0/344 (0%)
Product Issues
Device dislocation	1/348 (0.3%)		3/344 (0.9%)
Device malfunction	1/348 (0.3%)		0/344 (0%)
Embedded device	0/348 (0%)		1/344 (0.3%)
Psychiatric disorders
Confusional state	3/348 (0.9%)		0/344 (0%)
Delirium	1/348 (0.3%)		1/344 (0.3%)
Suicidal ideation	0/348 (0%)		1/344 (0.3%)
Suicide attempt	0/348 (0%)		1/344 (0.3%)
Renal and urinary disorders
Acute kidney injury	12/348 (3.4%)		11/344 (3.2%)
Hydronephrosis	1/348 (0.3%)		0/344 (0%)
Nephritis	1/348 (0.3%)		0/344 (0%)
Oliguria	0/348 (0%)		1/344 (0.3%)
Renal disorder	1/348 (0.3%)		0/344 (0%)
Renal failure	0/348 (0%)		4/344 (1.2%)
Renal tubular necrosis	1/348 (0.3%)		0/344 (0%)
Urinary retention	0/348 (0%)		1/344 (0.3%)
Reproductive system and breast disorders
Scrotal oedema	0/348 (0%)		1/344 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/348 (0.3%)		0/344 (0%)
Acute respiratory failure	2/348 (0.6%)		1/344 (0.3%)
Asphyxia	1/348 (0.3%)		2/344 (0.6%)
Aspiration	1/348 (0.3%)		1/344 (0.3%)
Atelectasis	0/348 (0%)		1/344 (0.3%)
Chronic obstructive pulmonary disease	0/348 (0%)		1/344 (0.3%)
Cough	0/348 (0%)		1/344 (0.3%)
Dyspnoea	5/348 (1.4%)		7/344 (2%)
Haemoptysis	2/348 (0.6%)		3/344 (0.9%)
Hypoxia	1/348 (0.3%)		3/344 (0.9%)
Laryngeal haemorrhage	0/348 (0%)		1/344 (0.3%)
Laryngeal inflammation	2/348 (0.6%)		0/344 (0%)
Laryngeal necrosis	0/348 (0%)		1/344 (0.3%)
Laryngeal oedema	5/348 (1.4%)		4/344 (1.2%)
Laryngeal stenosis	2/348 (0.6%)		0/344 (0%)
Obstructive airways disorder	0/348 (0%)		1/344 (0.3%)
Oropharyngeal pain	1/348 (0.3%)		2/344 (0.6%)
Pharyngeal haemorrhage	2/348 (0.6%)		2/344 (0.6%)
Pharyngeal inflammation	2/348 (0.6%)		0/344 (0%)
Pharyngeal necrosis	1/348 (0.3%)		0/344 (0%)
Pharyngeal oedema	1/348 (0.3%)		0/344 (0%)
Pharyngeal stenosis	1/348 (0.3%)		0/344 (0%)
Pharyngeal ulceration	2/348 (0.6%)		0/344 (0%)
Pneumonia aspiration	5/348 (1.4%)		5/344 (1.5%)
Pneumonitis	6/348 (1.7%)		1/344 (0.3%)
Pneumothorax	1/348 (0.3%)		2/344 (0.6%)
Productive cough	1/348 (0.3%)		1/344 (0.3%)
Pulmonary embolism	2/348 (0.6%)		0/344 (0%)
Respiratory arrest	0/348 (0%)		1/344 (0.3%)
Respiratory distress	2/348 (0.6%)		1/344 (0.3%)
Respiratory failure	0/348 (0%)		2/344 (0.6%)
Respiratory tract oedema	1/348 (0.3%)		0/344 (0%)
Stridor	1/348 (0.3%)		1/344 (0.3%)
Tonsillar haemorrhage	1/348 (0.3%)		0/344 (0%)
Tracheal stenosis	1/348 (0.3%)		1/344 (0.3%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/348 (0.3%)		0/344 (0%)
Rash	1/348 (0.3%)		0/344 (0%)
Surgical and medical procedures
Gastrostomy	1/348 (0.3%)		0/344 (0%)
Vascular disorders
Capillary leak syndrome	0/348 (0%)		1/344 (0.3%)
Circulatory collapse	0/348 (0%)		1/344 (0.3%)
Embolism	1/348 (0.3%)		0/344 (0%)
Haematoma	0/348 (0%)		1/344 (0.3%)
Haemorrhage	1/348 (0.3%)		1/344 (0.3%)
Hypotension	2/348 (0.6%)		4/344 (1.2%)
Lymphorrhoea	0/348 (0%)		1/344 (0.3%)
Phlebitis superficial	1/348 (0.3%)		0/344 (0%)
Shock	1/348 (0.3%)		0/344 (0%)
Vascular rupture	1/348 (0.3%)		0/344 (0%)
Vasculitis	1/348 (0.3%)		0/344 (0%)
Venous haemorrhage	0/348 (0%)		1/344 (0.3%)
Other (Not Including Serious) Adverse Events
	Avelumab + Standard of Care Chemotherapy (SOC CRT)		Placebo + SOC CRT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	344/348 (98.9%)		340/344 (98.8%)
Blood and lymphatic system disorders
Anaemia	206/348 (59.2%)		192/344 (55.8%)
Leukopenia	64/348 (18.4%)		46/344 (13.4%)
Lymphopenia	33/348 (9.5%)		27/344 (7.8%)
Neutropenia	102/348 (29.3%)		98/344 (28.5%)
Thrombocytopenia	45/348 (12.9%)		41/344 (11.9%)
Ear and labyrinth disorders
Ear pain	23/348 (6.6%)		12/344 (3.5%)
Hypoacusis	29/348 (8.3%)		30/344 (8.7%)
Tinnitus	59/348 (17%)		66/344 (19.2%)
Endocrine disorders
Hyperthyroidism	24/348 (6.9%)		7/344 (2%)
Hypothyroidism	51/348 (14.7%)		45/344 (13.1%)
Gastrointestinal disorders
Abdominal pain	11/348 (3.2%)		20/344 (5.8%)
Abdominal pain upper	14/348 (4%)		18/344 (5.2%)
Constipation	178/348 (51.1%)		155/344 (45.1%)
Diarrhoea	83/348 (23.9%)		66/344 (19.2%)
Dry mouth	151/348 (43.4%)		158/344 (45.9%)
Dyspepsia	23/348 (6.6%)		21/344 (6.1%)
Dysphagia	143/348 (41.1%)		152/344 (44.2%)
Nausea	210/348 (60.3%)		199/344 (57.8%)
Odynophagia	62/348 (17.8%)		48/344 (14%)
Oral pain	39/348 (11.2%)		43/344 (12.5%)
Stomatitis	92/348 (26.4%)		96/344 (27.9%)
Vomiting	112/348 (32.2%)		121/344 (35.2%)
General disorders
Asthenia	63/348 (18.1%)		58/344 (16.9%)
Chills	39/348 (11.2%)		7/344 (2%)
Fatigue	116/348 (33.3%)		127/344 (36.9%)
Localised oedema	22/348 (6.3%)		20/344 (5.8%)
Malaise	20/348 (5.7%)		23/344 (6.7%)
Mucosal inflammation	146/348 (42%)		131/344 (38.1%)
Oedema peripheral	19/348 (5.5%)		16/344 (4.7%)
Pain	23/348 (6.6%)		28/344 (8.1%)
Pyrexia	87/348 (25%)		45/344 (13.1%)
Infections and infestations
Oral candidiasis	25/348 (7.2%)		31/344 (9%)
Pneumonia	36/348 (10.3%)		25/344 (7.3%)
Upper respiratory tract infection	24/348 (6.9%)		21/344 (6.1%)
Injury, poisoning and procedural complications
Infusion related reaction	24/348 (6.9%)		6/344 (1.7%)
Radiation skin injury	135/348 (38.8%)		136/344 (39.5%)
Investigations
Alanine aminotransferase increased	56/348 (16.1%)		30/344 (8.7%)
Amylase increased	22/348 (6.3%)		10/344 (2.9%)
Aspartate aminotransferase increased	55/348 (15.8%)		26/344 (7.6%)
Blood alkaline phosphatase increased	22/348 (6.3%)		9/344 (2.6%)
Blood creatinine increased	88/348 (25.3%)		73/344 (21.2%)
Blood urea increased	18/348 (5.2%)		17/344 (4.9%)
Gamma-glutamyltransferase increased	23/348 (6.6%)		15/344 (4.4%)
Lymphocyte count decreased	40/348 (11.5%)		42/344 (12.2%)
Neutrophil count decreased	64/348 (18.4%)		60/344 (17.4%)
Platelet count decreased	40/348 (11.5%)		33/344 (9.6%)
Weight decreased	157/348 (45.1%)		171/344 (49.7%)
White blood cell count decreased	69/348 (19.8%)		64/344 (18.6%)
Metabolism and nutrition disorders
Decreased appetite	128/348 (36.8%)		124/344 (36%)
Dehydration	31/348 (8.9%)		29/344 (8.4%)
Hyperglycaemia	31/348 (8.9%)		33/344 (9.6%)
Hyperkalaemia	34/348 (9.8%)		32/344 (9.3%)
Hypoalbuminaemia	42/348 (12.1%)		36/344 (10.5%)
Hypocalcaemia	29/348 (8.3%)		23/344 (6.7%)
Hypokalaemia	87/348 (25%)		71/344 (20.6%)
Hypomagnesaemia	93/348 (26.7%)		84/344 (24.4%)
Hyponatraemia	83/348 (23.9%)		68/344 (19.8%)
Hypophosphataemia	23/348 (6.6%)		32/344 (9.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	17/348 (4.9%)		20/344 (5.8%)
Neck pain	30/348 (8.6%)		25/344 (7.3%)
Nervous system disorders
Dizziness	41/348 (11.8%)		33/344 (9.6%)
Dysgeusia	106/348 (30.5%)		119/344 (34.6%)
Headache	44/348 (12.6%)		41/344 (11.9%)
Neuropathy peripheral	11/348 (3.2%)		28/344 (8.1%)
Psychiatric disorders
Anxiety	26/348 (7.5%)		34/344 (9.9%)
Depression	10/348 (2.9%)		18/344 (5.2%)
Insomnia	57/348 (16.4%)		47/344 (13.7%)
Renal and urinary disorders
Acute kidney injury	18/348 (5.2%)		22/344 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	74/348 (21.3%)		63/344 (18.3%)
Dysphonia	51/348 (14.7%)		47/344 (13.7%)
Dyspnoea	33/348 (9.5%)		33/344 (9.6%)
Hiccups	26/348 (7.5%)		23/344 (6.7%)
Oropharyngeal pain	75/348 (21.6%)		92/344 (26.7%)
Pharyngeal inflammation	24/348 (6.9%)		23/344 (6.7%)
Productive cough	40/348 (11.5%)		31/344 (9%)
Skin and subcutaneous tissue disorders
Alopecia	22/348 (6.3%)		20/344 (5.8%)
Dermatitis	52/348 (14.9%)		42/344 (12.2%)
Dry skin	18/348 (5.2%)		24/344 (7%)
Erythema	24/348 (6.9%)		27/344 (7.8%)
Pruritus	38/348 (10.9%)		24/344 (7%)
Rash	43/348 (12.4%)		36/344 (10.5%)
Vascular disorders
Hypertension	32/348 (9.2%)		28/344 (8.1%)
Hypotension	22/348 (6.3%)		14/344 (4.1%)
Lymphoedema	18/348 (5.2%)		15/344 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.