TerminatedNCT02952586Updated Sep 22, 2021Results posted

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)

A Phase 3 interventional study of Avelumab and Chemoradiation in Squamous Cell Carcinoma of the Head and Neck, sponsored by Pfizer. Terminated at 316 sites in 22 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-22.

Sponsored by Pfizer · Phase 3, Interventional, and Treatment

Why this study was terminated

The trial prematurely terminated as recommended by the E-DMC because the boundary for futility has been crossed.

Phase: Phase 3
Study type: Interventional
Enrollment: 697
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

Squamous Cell Carcinoma of the Head and Neck

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In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 697 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

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Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: 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

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).

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 697 participants (actual)

Study arms

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
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

Interventions

DrugAvelumab
Avelumab + SOC Chemoradiation
OtherChemoradiation
Cisplatin + Radiation Therapy

What researchers measure

Primary outcomes

Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator
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)

Secondary outcomes

Overall Survival (OS)
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)
Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site
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)
Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator
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)
Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator
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)
Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator
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)
Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator
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)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
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
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters
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
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure
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)
Change From Baseline in Vital Sign - Pulse Rate
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)
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase
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)
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase
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)
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
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)
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
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)
Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells
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)
Percentage of Participants With Positive and Negative Pathology of Neck Dissection
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)
Maximum Plasma Concentration (Cmax) of Avelumab
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)
Predose Plasma Concentration (Ctrough) of Avelumab
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)
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin
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
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin
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
Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin
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
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin
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
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
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
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

Results

Posted Feb 24, 2021

Participant flow

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.

Lead-In Phase (7 Days)

Participant flow — Lead-In Phase (7 Days)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	350	347
Safety analysis set	348	344
Completed	345	343
Not completed	5	4
Withdrew: Death	0	1
Withdrew: Adverse event	3	0
Withdrew: No longer met eligibility criteria	0	1
Withdrew: Withdrawal by subject	2	2

CRT for Avelumab or Placebo (63 Days)

Participant flow — CRT for Avelumab or Placebo (63 Days)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	345	340
Completed	312	313
Not completed	33	27
Withdrew: Death	5	8
Withdrew: Adverse event	12	12
Withdrew: Physician decision	2	1
Withdrew: Global deterioration of health status	1	0
Withdrew: Withdrawal by subject	10	4
Withdrew: Lost to follow-up	1	1
Withdrew: Other	2	1

CRT for Cisplatin (63 Days)

Participant flow — CRT for Cisplatin (63 Days)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	345	340
Completed	234	236
Not completed	111	104
Withdrew: Death	3	8
Withdrew: Adverse event	82	81
Withdrew: Physician decision	12	10
Withdrew: Global deterioration of health status	1	0
Withdrew: Withdrawal by subject	11	3
Withdrew: Lost to follow-up	1	1
Withdrew: Other	1	1

CRT for IMRT (63 Days)

Participant flow — CRT for IMRT (63 Days)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	345	340
Completed	322	320
Not completed	23	20
Withdrew: Death	5	8
Withdrew: Adverse event	5	5
Withdrew: Global deterioration of health status	1	0
Withdrew: Withdrawal by subject	10	6
Withdrew: Lost to follow-up	1	1
Withdrew: Other	1	0

Maintenance Phase (12 Months)

Participant flow — Maintenance Phase (12 Months)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	291	304
Completed	139	177
Not completed	152	127
Withdrew: Death	17	11
Withdrew: Progressive disease	60	54
Withdrew: Adverse event	24	21
Withdrew: Non-compliance with study drug	1	1
Withdrew: Physician decision	1	1
Withdrew: Global deterioration of health status	14	5
Withdrew: Withdrawal by subject	31	25
Withdrew: Lost to follow-up	1	2
Withdrew: Other	2	1
Withdrew: Study terminated by sponsor	1	6

Follow-Up Phase (90 Days)

Participant flow — Follow-Up Phase (90 Days)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	266	284
Completed	208	216
Not completed	58	68
Withdrew: Death	12	10
Withdrew: Withdrawal by subject	6	2
Withdrew: Lost to follow-up	1	1
Withdrew: Other	7	5
Withdrew: Study terminated by sponsor	32	50

LT Follow-up (up to 45 Months)

Participant flow — LT Follow-up (up to 45 Months)
Milestone	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Started	247	237
Completed	0	0
Not completed	247	237
Withdrew: Death	51	31
Withdrew: Withdrawal by subject	7	1
Withdrew: Lost to follow-up	2	4
Withdrew: Study terminated by sponsor	187	201

Outcome measures

PrimaryProgression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator

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)
Reported as:: Median · months

Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator
months	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator	NA (16.9 to NA)	NA (23.0 to NA)

Statistical analysis

Avelumab + Standard of Care Chemotherapy (SOC CRT) vs Placebo + SOC CRT · Log Rank · p = 0.9199 (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).) · Hazard ratio (hr): 1.21 · 95% CI 0.928 to 1.573

SecondaryOverall Survival (OS)

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)
Reported as:: Median · months

Overall Survival (OS)
months	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Overall Survival (OS)	NA (NA to NA)	NA (NA to NA)

Statistical analysis

Avelumab + Standard of Care Chemotherapy (SOC CRT) vs Placebo + SOC CRT · Log Rank · p = 0.9372 (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).) · Hazard ratio (hr): 1.31 · 95% CI 0.927 to 1.849

SecondaryPathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site

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)
Reported as:: Number · percentage of participants

Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site
percentage of participants	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site	0 (0.0 to 45.9)	14.3 (0.4 to 57.9)

SecondaryTime to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator

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)
Reported as:: Median · months

Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator
months	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator	NA (22.4 to NA)	NA (25.0 to NA)

Statistical analysis

Avelumab + Standard of Care Chemotherapy (SOC CRT) vs Placebo + SOC CRT · Log Rank · p = 0.9316 (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).) · Hazard ratio (hr): 1.25 · 95% CI 0.930 to 1.694

SecondaryObjective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator

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)
Reported as:: Number · percentage of participants

Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator
percentage of participants	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator	74.0 (69.1 to 78.5)	74.9 (70.0 to 79.4)

Statistical analysis

Avelumab + Standard of Care Chemotherapy (SOC CRT) vs Placebo + SOC CRT · Cochran-Mantel-Haenszel · p = 0.6229 (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).) · Odds ratio (or): 0.947 · 95% CI 0.663 to 1.352

SecondaryTime to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator

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)
Reported as:: Median · months

Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator
months	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator	NA (22.8 to NA)	NA (NA to NA)

Statistical analysis

Avelumab + Standard of Care Chemotherapy (SOC CRT) vs Placebo + SOC CRT · Log Rank · p = 0.9061 (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).) · Hazard ratio (hr): 1.21 · 95% CI 0.909 to 1.624

SecondaryDuration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator

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)
Reported as:: Median · months

Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator
months	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator	NA (NA to NA)	NA (NA to NA)

SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

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
Reported as:: Count of participants · Participants

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Participants	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Grade 1	10	8
Grade 2	30	53
Grade 3	224	215
Grade 4	59	49
Grade 5	22	17

SecondaryNumber of Participants With Shift From Baseline in Clinical Laboratory Parameters

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
Reported as:: Count of participants · Participants

Number of Participants With Shift From Baseline in Clinical Laboratory Parameters
Participants	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Anemia: New or worsened to grade >=1	314	311
Anemia: New or worsened to grade >=3	42	49
Lymphocyte Count Decreased: New or worsened to grade >=1	336	330
Lymphocyte Count (LC) Decreased: New or worsened to grade >=3	279	284
Lymphocyte Count (LC) Increased: New or worsened to grade >=1	7	7
Lymphocyte Count Increased: New or worsened to grade >=3	0	0
Neutrophil Count (NC) Decreased: New or worsened to grade >=1	257	237
Neutrophil Count Decreased: New or worsened to grade >=3	120	101
Platelet Count (PC) Decreased : New or worsened to grade >=1	157	154
Platelet Count Decreased: New or worsened to grade >=3	20	7
White Blood Cell (WBC) Decreased: New or worsened to grade >=1	309	307
White Blood Cell Decreased: New or worsened to grade >=3	121	129
Alanine aminotransferase (ALT) increased: New or worsened to grade >=1	152	135
ALT increased: New or worsened to grade >=3	13	2
Alkaline phosphatase increased (ALP): New or worsened to grade >=1	72	49
Alkaline phosphatase increased: New or worsened to grade >=3	1	1
Aspartate aminotransferase (AST) increased: New or worsened to grade >=1	146	111
Aspartate aminotransferase increased: New or worsened to grade >=3	11	4
Blood bilirubin (BB) increased (BB): New or worsened to grade >=1	58	54
Blood bilirubin increased: New or worsened to grade >=3	9	4
Cholesterol (CH) high: New or worsened to grade >=1	25	21
Cholesterol high: New or worsened to grade >=3	0	0
CPK increased: New or worsened to grade >=1	7	7
CPK increased: New or worsened to grade >=3	0	1
Creatinine increased: New or worsened to grade >=1	334	325
Creatinine increased: New or worsened to grade >=3	36	37
GGT increased: New or worsened to grade >=1	37	23
GGT increased: New or worsened to grade >=3	10	5
Hypercalcemia: New or worsened to grade >=1	67	59
Hypercalcemia: New or worsened to grade >=3	1	5
Hyperglycemia: New or worsened to grade >=1	144	137
Hyperglycemia: New or worsened to grade >=3	28	29
Hyperkalemia: New or worsened to grade >=1	106	113
Hyperkalemia: New or worsened to grade >=3	9	17
Hypermagnesemia: New or worsened to grade >=1	39	40
Hypermagnesemia: New or worsened to grade >=3	10	10
Hypernatremia: New or worsened to grade >=1	22	20
Hypernatremia: New or worsened to grade >=3	1	0
Hypertriglyceridemia: New or worsened to grade >=1	35	26
Hypertriglyceridemia: New or worsened to grade >=3	1	2
Hypoalbuminemia: New or worsened to grade >=1	195	170
Hypoalbuminemia: New or worsened to grade >=3	7	5
Hypocalcemia: New or worsened to grade >=1	82	88
Hypocalcemia: New or worsened to grade >=3	8	14
Hypoglycemia: New or worsened to grade >=1	56	44
Hypoglycemia: New or worsened to grade >=3	2	2
Hypokalemia: New or worsened to grade >=1	140	122
Hypokalemia: New or worsened to grade >=3	55	49
Hypomagnesemia: New or worsened to grade >=1	180	158
Hypomagnesemia: New or worsened to grade >=3	8	12
Hyponatremia: New or worsened to grade >=1	232	212
Hyponatremia: New or worsened to grade >=3	74	70
Hypophosphatemia: New or worsened to grade >=1	108	100
Hypophosphatemia: New or worsened to grade >=3	21	19
Lipase increased: New or worsened to grade >=1	19	13
Lipase increased: New or worsened to grade >=3	11	3
Serum amylase increased: New or worsened to grade >=1	13	10
Serum amylase increased: New or worsened to grade >=3	9	5

SecondaryChange From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure

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)
Reported as:: Mean · millimeter of mercury

Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure
millimeter of mercury	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
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

SecondaryChange From Baseline in Vital Sign - Pulse Rate

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)
Reported as:: Mean · beats per minute

Change From Baseline in Vital Sign - Pulse Rate
beats per minute	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
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

SecondaryChange From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase

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)
Reported as:: Mean · units on a scale

Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase
units on a scale	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
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

SecondaryChange From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase

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)
Reported as:: Mean · units on a scale

Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase
units on a scale	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
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

SecondaryChange From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase

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)
Reported as:: Mean · units on a scale

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
units on a scale	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
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

SecondaryProgrammed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)

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)
Reported as:: Mean · % of PD-L1+ cells

Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
% of PD-L1+ cells	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Positive Immune Cells	7.4 ± 7.06	8.3 ± 8.47
Tumor Staining Cells	12.7 ± 24.90	18.3 ± 31.12

SecondaryMean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells

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)
Reported as:: Mean · % of tumor area occupied by CD8+ cells

Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells
% of tumor area occupied by CD8+ cells	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells	4.9 ± 6.03	5.8 ± 6.55

SecondaryPercentage of Participants With Positive and Negative Pathology of Neck Dissection

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)
Reported as:: Number · percentage of participants

Percentage of Participants With Positive and Negative Pathology of Neck Dissection
percentage of participants	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Negative Pathology	7.14	26.70
Positive pathology	71.43	40.00
Pathology not reported	21.43	33.30

SecondaryMaximum Plasma Concentration (Cmax) of Avelumab

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)
Reported as:: Geometric mean · microgram per milliliter

Maximum Plasma Concentration (Cmax) of Avelumab
microgram per milliliter	Avelumab + Standard of Care Chemotherapy (SOC CRT)
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

SecondaryPredose Plasma Concentration (Ctrough) of Avelumab

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)
Reported as:: Geometric mean · microgram per milliliter

Predose Plasma Concentration (Ctrough) of Avelumab
microgram per milliliter	Avelumab + Standard of Care Chemotherapy (SOC CRT)
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

SecondaryDose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin

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
Reported as:: Geometric mean · nanogram per milliliter per milligram

Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin
nanogram per milliliter per milligram	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Total Cisplastin	26.23 ± 36	25.33 ± 26
Free Cisplastin	11.84 ± 29	7.286 ± 96

SecondaryDose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin

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
Reported as:: Geometric mean · nanogram*hour/milliliter/milligram

Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin
nanogram*hour/milliliter/milligram	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Total Cisplatin	299.1 ± 30	332.7 ± 17
Free Cisplatin	36.53 ± 51	29.08 ± 49

SecondaryMaximum Plasma Concentration (Cmax) of Total and Free Cisplatin

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
Reported as:: Geometric mean · nanogram per milliliter

Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin
nanogram per milliliter	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Total Cisplatin	3781 ± 44	4001 ± 34
Free Cisplatin	1710 ± 53	1151 ± 109

SecondaryTime to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin

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
Reported as:: Median · hour

Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin
hour	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
Total Cisplatin	1.000 (0.500 to 2.40)	1.170 (0.983 to 24.0)
Free Cisplatin	1.000 (0.500 to 1.17)	1.000 (0.500 to 2.12)

SecondaryNumber of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status

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
Reported as:: Count of participants · Participants

Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
Participants	Avelumab + Standard of Care Chemotherapy (SOC CRT)
ADA never-positive	277
ADA ever-positive	54

SecondaryNumber 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

No measurements were reported for this outcome.

Adverse events

Collected over Baseline up to 44 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Avelumab + Standard of Care Chemotherapy (SOC CRT)	86/348 (24.7%)	184/348 (52.9%)	344/348 (98.9%)
Placebo + SOC CRT	62/344 (18%)	177/344 (51.5%)	340/344 (98.8%)

Most frequent serious events

Showing 10 of 266

Most frequent serious events
Event	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
PneumoniaInfections and infestations	25/348	20/344
DehydrationMetabolism and nutrition disorders	9/348	15/344
DysphagiaGastrointestinal disorders	15/348	13/344
VomitingGastrointestinal disorders	11/348	13/344
AnaemiaBlood and lymphatic system disorders	8/348	12/344
PyrexiaGeneral disorders	12/348	3/344
Acute kidney injuryRenal and urinary disorders	12/348	11/344
NauseaGastrointestinal disorders	7/348	9/344
Febrile neutropeniaBlood and lymphatic system disorders	9/348	5/344
HyponatraemiaMetabolism and nutrition disorders	4/348	7/344

Most frequent other events

Showing 10 of 84

Most frequent other events
Event	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
NauseaGastrointestinal disorders	210/348	199/344
AnaemiaBlood and lymphatic system disorders	206/348	192/344
ConstipationGastrointestinal disorders	178/348	155/344
Weight decreasedInvestigations	157/348	171/344
Dry mouthGastrointestinal disorders	151/348	158/344
DysphagiaGastrointestinal disorders	143/348	152/344
Mucosal inflammationGeneral disorders	146/348	131/344
Radiation skin injuryInjury, poisoning and procedural complications	135/348	136/344
FatigueGeneral disorders	116/348	127/344
Decreased appetiteMetabolism and nutrition disorders	128/348	124/344

Baseline characteristics

The full analysis set (FAS) included all randomized participants.

Age, Continuous
Age, Continuous(years)	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT	Total
Mean	59.36 ± 8.56	58.88 ± 9.09	59.12 ± 8.83

Sex: Female, Male
Sex: Female, Male(Participants)	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT	Total
Female	60	62	122
Male	290	285	575

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT	Total
Hispanic or Latino	13	8	21
Not Hispanic or Latino	312	312	624
Unknown or Not Reported	25	27	52

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT	Total
Black or African American	9	10	19
American Indian or Alaska Native	1	0	1
Asian	102	86	188
Native Hawaiian or Other Pacific Islander	0	1	1
White	224	229	453
Other	14	21	35

Study locations

316 sites

Highlands Oncology Group
Fayetteville, Arkansas 72703, United States
Highlands Oncology Group
Rogers, Arkansas 72758, United States
Highlands Oncology Group
Springdale, Arkansas 72762, United States
The Oncology Institute of Hope and Innovation
Anaheim, California 92801, United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
Bakersfield, California 93309, United States
Beverly Hills Cancer Center
Beverly Hills, California 90211, United States
Tower Hematology Oncology Medical Group
Beverly Hills, California 90211, United States
UCSD Radiation Oncology South Bay, Cancer Treatment Centers
Chula Vista, California 91914, United States
City of Hope Corona
Corona, California 92879, United States
Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.
Corona, California 92879, United States
The Oncology Institute of Hope and Innovation
Downey, California 90241, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California 91010, United States
The Oncology Institute of Hope and Innovation
Glendale, California 91204, United States
UC San Diego Medical Center- La Jolla (Thornton Hospital)
La Jolla, California 92037, United States
UC San Diego Moores Cancer Center
La Jolla, California 92093, United States
City of Hope Antelope Valley
Lancaster, California 93534, United States
The Oncology Institute of Hope and Innovation
Long Beach, California 90805, United States
The Oncology Institute of Hope and Innovation
Los Angeles, California 90033, United States
Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California 90048, United States
The Oncology Institute of Hope and Innovation
Lynwood, California 90262, United States
The Oncology Institute of Hope and Innovation
Montebello, California 90640, United States
UC Irvine Medical Center
Orange, California 92868-3201, United States
Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.
Riverside, California 92501, United States
UC San Diego Medical Center- Hillcrest
San Diego, California 92103, United States
The Oncology Institute of Hope and Innovation
Santa Ana, California 92705, United States
City of Hope South Pasadena
South Pasadena, California 91030, United States
The Oncology Institute of Hope and Innovation
Torrance, California 90503, United States
The Oncology Institute of Hope and Innovation
West Covina, California 91790, United States
The Oncology Institute of Hope and Innovation
Whittier, California 90602, United States
Rocky Mountain Lions Eye Institute
Aurora, Colorado 80045, United States
University of Colorado Denver CTO/CTRC
Aurora, Colorado 80045, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion
Aurora, Colorado 80045, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion
Aurora, Colorado 80045, United States
University Of Colorado Hospital Cancer Center
Aurora, Colorado 80045, United States
Cypress Hematology & Oncology
Denver, Colorado 80210, United States
Cypress Hematology and Oncology
Parker, Colorado 80138, United States
Sylvester at Coral Gables
Coral Gables, Florida 33146, United States
Sylvester at Deerfield Beach
Deerfield Beach, Florida 33442, United States
Specialist Global LLC
Hialeah, Florida 33012, United States
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida 33021, United States
Hollis Cancer Center
Lakeland, Florida 33805, United States
Sylvester Comprehensive Cancer Center
Miami, Florida 33136, United States
Memorial Cancer Institute at Memorial Hospital West
Pembroke Pines, Florida 33028, United States
Sylvester at Plantation
Plantation, Florida 33324, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612, United States
Primary Healthcare Associates
Flossmoor, Illinois 60422, United States
Ingalls Memorial Hospital
Harvey, Illinois 60426, United States
Primary Healthcare Associates
Harvey, Illinois 60426, United States
Primary Healthcare Associates
Tinley Park, Illinois 60477, United States
IU Health Arnett Cancer Center
Lafayette, Indiana 47904, United States
Kansas City VA Radiation Oncology Clinic
Overland Park, Kansas 66212, United States
Ashland-Bellefonte Cancer Center
Ashland, Kentucky 41101, United States
Norton Cancer Institute
Louisville, Kentucky 40202, United States
Norton Hospital
Louisville, Kentucky 40202, United States
University Medical Center, Inc.
Louisville, Kentucky 40202, United States
Norton Brownsboro Hospital
Louisville, Kentucky 40241, United States
Norton Cancer Institute
Louisville, Kentucky 40241, United States
Highlands Cancer Center
Prestonsburg, Kentucky 41653, United States
Maryland Proton Treatment Center
Baltimore, Maryland 21201, United States
University of Maryland School of Medicine
Baltimore, Maryland 21201, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland 21201, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215, United States
Karmanos Cancer Institute
Detroit, Michigan 48201, United States
Henry Ford Hospital
Detroit, Michigan 48202, United States
Karmanos Cancer Institute
Farmington Hills, Michigan 48334, United States
Herbert-Herman Cancer Center, Sparrow Hospital
Lansing, Michigan 48912, United States
University of Missouri- Ellis Fischel Cancer Center
Columbia, Missouri 65212, United States
Siteman Cancer Center - West County
Creve Coeur, Missouri 63141, United States
Kansas City VA Medical Center
Kansas City, Missouri 64128, United States
Barnes-Jewish Hospital
Saint Louis, Missouri 63110, United States
Washington University School of Medicine Siteman Cancer Center
Saint Louis, Missouri 63110, United States
Siteman Cancer Center - South County
Saint Louis, Missouri 63129, United States
Siteman Cancer Center- St. Peters
Saint Peters, Missouri 63376, United States
Department of Radiation Oncology Methodist Hospital
Omaha, Nebraska 68114, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska 68114, United States
Memorial Sloan Kettering Cancer Center-Basking Ridge
Basking Ridge, New Jersey 07920, United States
Hackensack University Medical Center
Hackensack, New Jersey 07601, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey 07601, United States
Memorial Sloan Kettering Cancer Center- Monmouth
Middletown, New Jersey 07748, United States
Memorial Sloan Kettering Cancer Center- Bergen
Montvale, New Jersey 07645, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico 87131, United States
Montefiore-Einstein Center for Cancer Care
Bronx, New York 10461, United States
Montefiore Medical Center
Bronx, New York 10467, United States
Memorial Sloan Kettering Cancer Center Commack
Commack, New York 11725, United States
Memorial Sloan Kettering Cancer Center Westchester
Harrison, New York 10604, United States
Bellevue Hospital Center
New York, New York 10016, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016, United States
NYU Langone Medical Center
New York, New York 10016, United States
NYU Langone Radiology
New York, New York 10016, United States
NYU Langone Radiology - Ambulatory Care Center East 41st Street
New York, New York 10017, United States
Memorial Sloan Kettering Cancer Center
New York, New York 10022, United States
Memorial Sloan Kettering Cancer Center: Breast and Imaging Center
New York, New York 10065, United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065, United States
Stony Brook University
Stony Brook, New York 11794-7007, United States
Stony Brook Cancer Center
Stony Brook, New York 11794, United States
Memorial Sloan Kettering Cancer Center- Nassau
Uniondale, New York 11553, United States
Oncology Specialists of Charlotte, PA
Charlotte, North Carolina 28204, United States
DJL Clinical Research, PLLC
Charlotte, North Carolina 28210, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina 27157, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106, United States

Showing the first 100 of 316 sites across 22 countries.

References and documents

Publications

Lee NY, Ferris RL, Psyrri A, Haddad RI, Tahara M, Bourhis J, Harrington K, Chang PM, Lin JC, Razaq MA, Teixeira MM, Lovey J, Chamois J, Rueda A, Hu C, Dunn LA, Dvorkin MV, De Beukelaer S, Pavlov D, Thurm H, Cohen E. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):450-462. doi: 10.1016/S1470-2045(20)30737-3. PubMed 33794205 ↗

Study documents

Study protocol · Jul 31, 2019
Statistical analysis plan · Aug 30, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 22, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02952586
Lead sponsor: Pfizer
Responsible party: Sponsor
First posted: Nov 2, 2016
Start date: Nov 28, 2016
Primary completion: Dec 23, 2019
Completion: Aug 25, 2020
Results posted: Feb 24, 2021
Last update: Sep 22, 2021

Study contacts

Pfizer CT.gov Call Center

study director · Pfizer

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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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)

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