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)

• ClinicalTrials.gov Identifier: NCT02952586
• Recruitment Status: Terminated
• First Posted: November 2, 2016
• Results First Posted: February 24, 2021
• Last Update Posted: September 22, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Squamous Cell Carcinoma of the Head and Neck
• Interventions: Drug: Avelumab; Other: Chemoradiation
• Enrollment: 697

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 Details

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
Reason Not Completed
Death	0	1
Adverse Event	3	0
No Longer Met Eligibility Criteria	0	1
Withdrawal by Subject	2	2
Period Title: CRT for Avelumab or Placebo (63 Days)
Started	345	340 [1]
Completed	312	313
Not Completed	33	27
Reason Not Completed
Death	5	8
Adverse Event	12	12
Physician Decision	2	1
Global Deterioration of Health Status	1	0
Withdrawal by Subject	10	4
Lost to Follow-up	1	1
Other	2	1
[1] All participants who did not withdraw from study after Lead-In phase, entered into CRT phase.
Period Title: CRT for Cisplatin (63 Days)
Started	345 [1]	340 [2]
Completed	234	236
Not Completed	111	104
Reason Not Completed
Death	3	8
Adverse Event	82	81
Physician Decision	12	10
Global Deterioration of Health Status	1	0
Withdrawal by Subject	11	3
Lost to Follow-up	1	1
Other	1	1
[1] Avelumab, Cisplatin, and IMRT were treatments in CRT phase.; [2] Placebo, Cisplatin, and IMRT were treatments in CRT phase.
Period Title: CRT for IMRT (63 Days)
Started	345 [1]	340 [2]
Completed	322	320
Not Completed	23	20
Reason Not Completed
Death	5	8
Adverse Event	5	5
Global Deterioration of Health Status	1	0
Withdrawal by Subject	10	6
Lost to Follow-up	1	1
Other	1	0
[1] Avelumab, Cisplatin, and IMRT were treatments in CRT phase.; [2] Placebo, Cisplatin, and IMRT were treatments in CRT phase.
Period Title: Maintenance Phase (12 Months)
Started	291 [1]	304 [1]
Completed	139	177
Not Completed	152	127
Reason Not Completed
Death	17	11
Progressive disease	60	54
Adverse Event	24	21
Non-compliance With Study Drug	1	1
Physician Decision	1	1
Global Deterioration of Health Status	14	5
Withdrawal by Subject	31	25
Lost to Follow-up	1	2
Other	2	1
Study Terminated by Sponsor	1	6
[1] All participants who did not withdraw from study after CRT phases, entered into maintenance phase.
Period Title: Follow-Up Phase (90 Days)
Started	266 [1]	284 [1]
Completed	208	216
Not Completed	58	68
Reason Not Completed
Death	12	10
Withdrawal by Subject	6	2
Lost to Follow-up	1	1
Other	7	5
Study Terminated by Sponsor	32	50
[1] Participants who did not withdraw study after previous phases, entered in short-term follow up phase.
Period Title: LT Follow-up (up to 45 Months)
Started	247 [1]	237 [1]
Completed	0	0
Not Completed	247	237
Reason Not Completed
Death	51	31
Withdrawal by Subject	7	1
Lost to Follow-up	2	4
Study Terminated by Sponsor	187	201
[1] Participants who did not withdraw study after previous phases, entered in long-term follow up phase.

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 Number of Baseline Participants		350	347	697
Baseline Analysis Population Description		The full analysis set (FAS) included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	350 participants	347 participants	697 participants
		59.36 (8.56)	58.88 (9.09)	59.12 (8.83)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	350 participants	347 participants	697 participants
	Female	60 17.1%	62 17.9%	122 17.5%
	Male	290 82.9%	285 82.1%	575 82.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	350 participants	347 participants	697 participants
	Hispanic or Latino	13 3.7%	8 2.3%	21 3.0%
	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; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	350 participants	347 participants	697 participants
	Black or African American	9 2.6%	10 2.9%	19 2.7%
	American Indian or Alaska Native	1 0.3%	0 0.0%	1 0.1%
	Asian	102 29.1%	86 24.8%	188 27.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 0.3%	1 0.1%
	White	224 64.0%	229 66.0%	453 65.0%
	Other	14 4.0%	21 6.1%	35 5.0%

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.
Overall Number of Participants Analyzed	350	347
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (16.9 to NA)	NA [2]; (23.0 to NA)

[1]

Median and upper limit of 95% CI were not reached at the time of primary completion date. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC Chemotherapy (CRT) arm was crossed and the study was terminated.

[2]

Median and upper limit of 95% CI were not reached at the time of primary completion date. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
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	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.928 to 1.573
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	350	347
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Median and 95% CI were not reached. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
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	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.927 to 1.849
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	6	7
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0.0 to 45.9)	14.3; (0.4 to 57.9)

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.
Overall Number of Participants Analyzed	350	347
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (22.4 to NA)	NA [1]; (25.0 to NA)

[1]

Median and upper limit of 95% CI were not reached. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
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	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.930 to 1.694
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	350	347
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	74.0; (69.1 to 78.5)	74.9; (70.0 to 79.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
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	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 95%; 0.663 to 1.352
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	350	347
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (22.8 to NA)	NA [2]; (NA to NA)

[1]

Median and upper limit of 95% CI were not reached. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.

[2]

Median and 95% CI were not reached. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
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	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.909 to 1.624
	Estimation Comments	[Not Specified]

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.
Overall Number of Participants Analyzed	259	260
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Median and 95% CI were not reached. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.

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.
Overall Number of Participants Analyzed	348	344
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 1	10 2.9%	8 2.3%
Grade 2	30 8.6%	53 15.4%
Grade 3	224 64.4%	215 62.5%
Grade 4	59 17.0%	49 14.2%
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.
Overall Number of Participants Analyzed		346	340
Measure Type: Count of Participants; Unit of Measure: Participants
Anemia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		314 90.8%	311 91.5%
Anemia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		42 12.1%	49 14.4%
Lymphocyte Count Decreased: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		336 97.1%	330 97.1%
Lymphocyte Count (LC) Decreased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		279 80.6%	284 83.5%
Lymphocyte Count (LC) Increased: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		7 2.0%	7 2.1%
Lymphocyte Count Increased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		0 0.0%	0 0.0%
Neutrophil Count (NC) Decreased: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		257 74.3%	237 69.7%
Neutrophil Count Decreased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		120 34.7%	101 29.7%
Platelet Count (PC) Decreased : New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		157 45.4%	154 45.3%
Platelet Count Decreased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		20 5.8%	7 2.1%
White Blood Cell (WBC) Decreased: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		309 89.3%	307 90.3%
White Blood Cell Decreased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		121 35.0%	129 37.9%
Alanine aminotransferase (ALT) increased: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		152 43.9%	135 39.7%
ALT increased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		13 3.8%	2 0.6%
Alkaline phosphatase increased (ALP): New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		72 20.8%	49 14.4%
Alkaline phosphatase increased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		1 0.3%	1 0.3%
Aspartate aminotransferase (AST) increased: New or worsened to grade >=1	Number Analyzed	345 participants	340 participants
		146 42.3%	111 32.6%
Aspartate aminotransferase increased: New or worsened to grade >=3	Number Analyzed	345 participants	340 participants
		11 3.2%	4 1.2%
Blood bilirubin (BB) increased (BB): New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		58 16.8%	54 15.9%
Blood bilirubin increased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		9 2.6%	4 1.2%
Cholesterol (CH) high: New or worsened to grade >=1	Number Analyzed	161 participants	164 participants
		25 15.5%	21 12.8%
Cholesterol high: New or worsened to grade >=3	Number Analyzed	161 participants	164 participants
		0 0.0%	0 0.0%
CPK increased: New or worsened to grade >=1	Number Analyzed	160 participants	156 participants
		7 4.4%	7 4.5%
CPK increased: New or worsened to grade >=3	Number Analyzed	160 participants	156 participants
		0 0.0%	1 0.6%
Creatinine increased: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		334 96.5%	325 95.6%
Creatinine increased: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		36 10.4%	37 10.9%
GGT increased: New or worsened to grade >=1	Number Analyzed	191 participants	193 participants
		37 19.4%	23 11.9%
GGT increased: New or worsened to grade >=3	Number Analyzed	191 participants	193 participants
		10 5.2%	5 2.6%
Hypercalcemia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		67 19.4%	59 17.4%
Hypercalcemia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		1 0.3%	5 1.5%
Hyperglycemia: New or worsened to grade >=1	Number Analyzed	345 participants	340 participants
		144 41.7%	137 40.3%
Hyperglycemia: New or worsened to grade >=3	Number Analyzed	345 participants	340 participants
		28 8.1%	29 8.5%
Hyperkalemia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		106 30.6%	113 33.2%
Hyperkalemia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		9 2.6%	17 5.0%
Hypermagnesemia: New or worsened to grade >=1	Number Analyzed	346 participants	339 participants
		39 11.3%	40 11.8%
Hypermagnesemia: New or worsened to grade >=3	Number Analyzed	346 participants	339 participants
		10 2.9%	10 2.9%
Hypernatremia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		22 6.4%	20 5.9%
Hypernatremia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		1 0.3%	0 0.0%
Hypertriglyceridemia: New or worsened to grade >=1	Number Analyzed	162 participants	161 participants
		35 21.6%	26 16.1%
Hypertriglyceridemia: New or worsened to grade >=3	Number Analyzed	162 participants	161 participants
		1 0.6%	2 1.2%
Hypoalbuminemia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		195 56.4%	170 50.0%
Hypoalbuminemia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		7 2.0%	5 1.5%
Hypocalcemia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		82 23.7%	88 25.9%
Hypocalcemia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		8 2.3%	14 4.1%
Hypoglycemia: New or worsened to grade >=1	Number Analyzed	345 participants	340 participants
		56 16.2%	44 12.9%
Hypoglycemia: New or worsened to grade >=3	Number Analyzed	345 participants	340 participants
		2 0.6%	2 0.6%
Hypokalemia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		140 40.5%	122 35.9%
Hypokalemia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		55 15.9%	49 14.4%
Hypomagnesemia: New or worsened to grade >=1	Number Analyzed	346 participants	339 participants
		180 52.0%	158 46.6%
Hypomagnesemia: New or worsened to grade >=3	Number Analyzed	346 participants	339 participants
		8 2.3%	12 3.5%
Hyponatremia: New or worsened to grade >=1	Number Analyzed	346 participants	340 participants
		232 67.1%	212 62.4%
Hyponatremia: New or worsened to grade >=3	Number Analyzed	346 participants	340 participants
		74 21.4%	70 20.6%
Hypophosphatemia: New or worsened to grade >=1	Number Analyzed	340 participants	339 participants
		108 31.8%	100 29.5%
Hypophosphatemia: New or worsened to grade >=3	Number Analyzed	340 participants	339 participants
		21 6.2%	19 5.6%
Lipase increased: New or worsened to grade >=1	Number Analyzed	161 participants	154 participants
		19 11.8%	13 8.4%
Lipase increased: New or worsened to grade >=3	Number Analyzed	161 participants	154 participants
		11 6.8%	3 1.9%
Serum amylase increased: New or worsened to grade >=1	Number Analyzed	159 participants	152 participants
		13 8.2%	10 6.6%
Serum amylase increased: New or worsened to grade >=3	Number Analyzed	159 participants	152 participants
		9 5.7%	5 3.3%

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.
Overall Number of Participants Analyzed		342	336
Mean (Standard Deviation); Unit of Measure: millimeter of mercury
DBP: Baseline	Number Analyzed	342 participants	336 participants
		77.8 (10.13)	78.1 (10.91)
Lead in Phase: DBP: Change at Day 1	Number Analyzed	2 participants	2 participants
		-3.0 (4.24)	-8.0 (11.31)
CRT Phase: DBP: Change at Day 1	Number Analyzed	332 participants	322 participants
		-1.5 (9.52)	-2.2 (9.91)
CRT Phase: DBP: Change at Day 8	Number Analyzed	323 participants	315 participants
		-3.8 (10.46)	-3.9 (10.99)
CRT Phase: DBP: Change at Day 22	Number Analyzed	313 participants	309 participants
		-4.2 (11.77)	-5.0 (10.95)
CRT Phase: DBP: Change at Day 25	Number Analyzed	310 participants	306 participants
		-3.4 (11.91)	-3.3 (11.44)
CRT Phase: DBP: Change at Day 39	Number Analyzed	309 participants	302 participants
		-5.7 (11.83)	-5.1 (12.14)
CRT Phase: DBP: Change at Day 43	Number Analyzed	293 participants	283 participants
		-5.0 (11.49)	-4.7 (11.76)
Maintenance Phase: DBP: Change at Cycle1/Day 1	Number Analyzed	282 participants	290 participants
		-4.8 (11.43)	-4.3 (11.67)
Maintenance Phase: DBP: Change at Cycle1/Day 15	Number Analyzed	265 participants	279 participants
		-3.7 (11.78)	-4.0 (10.96)
Maintenance Phase: DBP: Change at Cycle2/Day 1	Number Analyzed	266 participants	277 participants
		-3.3 (11.74)	-3.3 (12.31)
Maintenance Phase: DBP: Change at Cycle2/Day 15	Number Analyzed	255 participants	272 participants
		-2.7 (11.05)	-2.3 (11.82)
Maintenance Phase: DBP: Change at Cycle3/Day 1	Number Analyzed	249 participants	262 participants
		-2.7 (11.37)	-3.6 (11.42)
Maintenance Phase: DBP: Change at Cycle3/Day 15	Number Analyzed	234 participants	255 participants
		-2.7 (11.09)	-3.4 (11.10)
Maintenance Phase: DBP: Change at Cycle4/Day 1	Number Analyzed	222 participants	247 participants
		-2.2 (12.07)	-3.4 (11.42)
Maintenance Phase: DBP: Change at Cycle4/Day 15	Number Analyzed	216 participants	240 participants
		-2.4 (11.38)	-3.3 (11.54)
Maintenance Phase: DBP: Change at Cycle5/Day 1	Number Analyzed	210 participants	241 participants
		-2.8 (11.61)	-3.2 (10.88)
Maintenance Phase: DBP: Change at Cycle5/Day 15	Number Analyzed	204 participants	232 participants
		-2.5 (11.89)	-3.5 (10.69)
Maintenance Phase: DBP: Change at Cycle6/Day 1	Number Analyzed	201 participants	226 participants
		-3.1 (11.21)	-3.8 (11.28)
Maintenance Phase: DBP: Change at Cycle6/Day 15	Number Analyzed	198 participants	230 participants
		-3.8 (12.20)	-4.6 (11.43)
Maintenance Phase: DBP: Change at Cycle7/Day 1	Number Analyzed	190 participants	220 participants
		-4.1 (11.48)	-4.2 (11.52)
Maintenance Phase: DBP: Change at Cycle7/Day 15	Number Analyzed	185 participants	214 participants
		-3.8 (12.05)	-3.8 (10.88)
Maintenance Phase: DBP: Change at Cycle8/Day 1	Number Analyzed	173 participants	209 participants
		-2.9 (11.29)	-4.1 (10.95)
Maintenance Phase: DBP: Change at Cycle8/Day 15	Number Analyzed	167 participants	194 participants
		-3.4 (11.48)	-4.0 (12.29)
Maintenance Phase: DBP: Change at Cycle9/Day 1	Number Analyzed	169 participants	198 participants
		-3.1 (11.78)	-4.2 (10.98)
Maintenance Phase: DBP: Change at Cycle9/Day 15	Number Analyzed	162 participants	194 participants
		-2.1 (11.52)	-3.7 (12.07)
Maintenance Phase: DBP: Change at Cycle10/Day 1	Number Analyzed	161 participants	192 participants
		-2.2 (11.58)	-3.5 (11.54)
Maintenance Phase: DBP: Change at Cycle10/Day 15	Number Analyzed	159 participants	191 participants
		-2.5 (10.90)	-4.4 (11.69)
Maintenance Phase: DBP: Change at Cycle11/Day 1	Number Analyzed	146 participants	179 participants
		-2.7 (11.01)	-4.6 (11.23)
Maintenance Phase: DBP: Change at Cycle11/Day 15	Number Analyzed	139 participants	162 participants
		-2.9 (10.37)	-3.9 (10.22)
Maintenance Phase: DBP: Change at Cycle12/Day 1	Number Analyzed	125 participants	156 participants
		-2.1 (9.51)	-3.5 (11.40)
Maintenance Phase: DBP: Change at Cycle12/Day 15	Number Analyzed	115 participants	146 participants
		-3.3 (11.78)	-4.6 (11.19)
Maintenance Phase: DBP: Change at Cycle13/Day 1	Number Analyzed	105 participants	132 participants
		-2.0 (9.60)	-3.3 (11.49)
Maintenance Phase: DBP: Change at Cycle13/Day 15	Number Analyzed	92 participants	118 participants
		-1.1 (10.22)	-3.8 (11.44)
DBP: EOT	Number Analyzed	225 participants	210 participants
		-2.4 (11.96)	-3.2 (11.17)
SBP: Baseline	Number Analyzed	342 participants	336 participants
		129.8 (16.42)	130.5 (17.44)
Lead in Phase: SBP: Change at Day 1	Number Analyzed	2 participants	2 participants
		-5.5 (2.12)	12.5 (6.36)
CRT Phase: SBP: Change at Day 1	Number Analyzed	332 participants	322 participants
		-2.5 (15.32)	-3.5 (14.82)
CRT Phase: SBP: Change at Day 8	Number Analyzed	323 participants	315 participants
		-8.3 (17.78)	-8.0 (17.58)
CRT Phase: SBP: Change at Day 22	Number Analyzed	313 participants	309 participants
		-8.9 (18.54)	-8.4 (17.55)
CRT Phase: SBP: Change at Day 25	Number Analyzed	310 participants	306 participants
		-7.9 (19.06)	-5.8 (19.51)
CRT Phase: SBP: Change at Day 39	Number Analyzed	309 participants	302 participants
		-10.6 (20.51)	-10.3 (19.05)
CRT Phase: SBP: Change at Day 43	Number Analyzed	293 participants	283 participants
		-9.6 (18.53)	-9.2 (19.52)
Maintenance Phase: SBP: Change at Cycle1/Day 1	Number Analyzed	282 participants	290 participants
		-9.4 (17.97)	-9.4 (20.19)
Maintenance Phase: SBP: Change at Cycle1/Day 15	Number Analyzed	265 participants	279 participants
		-9.5 (17.73)	-8.2 (19.58)
Maintenance Phase: SBP: Change at Cycle2/Day 1	Number Analyzed	266 participants	277 participants
		-7.0 (18.03)	-7.8 (20.09)
Maintenance Phase: SBP: Change at /Cycle2/Day 15	Number Analyzed	255 participants	272 participants
		-7.9 (18.55)	-6.6 (19.73)
Maintenance Phase: SBP: Change at Cycle3/Day 1	Number Analyzed	249 participants	262 participants
		-7.3 (18.93)	-8.5 (18.04)
Maintenance Phase: SBP: Change at Cycle3/Day 15	Number Analyzed	234 participants	255 participants
		-8.3 (17.79)	-7.1 (19.90)
Maintenance Phase: SBP: Change at Cycle4/Day 1	Number Analyzed	222 participants	247 participants
		-8.4 (18.01)	-8.9 (18.41)
Maintenance Phase: SBP: Change at Cycle4/Day 15	Number Analyzed	216 participants	240 participants
		-6.2 (18.20)	-8.2 (19.62)
Maintenance Phase: SBP: Change at Maintenance/Cycle5/Day 1	Number Analyzed	210 participants	241 participants
		-7.6 (17.57)	-7.7 (18.69)
Maintenance Phase: SBP: Change at Cycle5/Day 15	Number Analyzed	204 participants	232 participants
		-8.4 (18.69)	-7.5 (18.49)
Maintenance Phase: SBP: Change at Cycle6/Day 1	Number Analyzed	201 participants	226 participants
		-7.6 (17.67)	-8.3 (18.96)
Maintenance Phase: SBP: Change at Cycle6/Day 15	Number Analyzed	198 participants	230 participants
		-7.1 (19.35)	-9.4 (19.56)
Maintenance Phase: SBP: Change at Cycle7/Day 1	Number Analyzed	190 participants	220 participants
		-9.0 (18.30)	-8.9 (18.96)
Maintenance Phase: SBP: Change at Cycle7/Day 15	Number Analyzed	185 participants	214 participants
		-8.7 (18.10)	-6.8 (18.73)
Maintenance Phase: SBP: Change at Cycle8/Day 1	Number Analyzed	173 participants	209 participants
		-6.5 (17.00)	-9.4 (18.65)
Maintenance Phase: SBP: Change at Cycle8/Day 15	Number Analyzed	167 participants	194 participants
		-6.8 (16.69)	-7.9 (18.21)
Maintenance Phase: SBP: Change at Cycle9/Day 1	Number Analyzed	169 participants	198 participants
		-6.1 (18.49)	-8.1 (18.41)
Maintenance Phase: SBP: Change at Cycle9/Day 15	Number Analyzed	162 participants	194 participants
		-6.3 (19.00)	-6.7 (20.28)
Maintenance Phase: SBP: Change at Cycle10/Day 1	Number Analyzed	161 participants	192 participants
		-6.1 (19.24)	-7.2 (18.63)
Maintenance Phase: SBP: Change at Cycle10/Day 15	Number Analyzed	159 participants	191 participants
		-5.6 (17.07)	-7.7 (18.76)
Maintenance Phase: SBP: Change at Cycle11/Day 1	Number Analyzed	146 participants	179 participants
		-6.3 (19.44)	-7.7 (18.86)
Maintenance Phase: SBP: Change at Cycle11/Day 15	Number Analyzed	139 participants	162 participants
		-6.3 (18.99)	-7.4 (18.65)
Maintenance Phase: SBP: Change at Cycle12/Day 1	Number Analyzed	125 participants	156 participants
		-6.8 (18.25)	-6.1 (20.21)
Maintenance Phase: SBP: Change at Cycle12/Day 15	Number Analyzed	115 participants	146 participants
		-7.1 (19.34)	-7.8 (19.12)
Maintenance Phase: SBP: Change at Cycle13/Day 1	Number Analyzed	105 participants	132 participants
		-5.8 (20.04)	-6.2 (18.54)
Maintenance Phase: SBP: Change at Cycle13/Day 15	Number Analyzed	92 participants	118 participants
		-4.9 (18.82)	-5.6 (19.00)
SBP: EOT	Number Analyzed	225 participants	210 participants
		-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.
Overall Number of Participants Analyzed		342	336
Mean (Standard Deviation); Unit of Measure: beats per minute
Baseline	Number Analyzed	342 participants	336 participants
		79.9 (13.72)	86.0 (43.0)
Lead in Phase: Change at Day 1	Number Analyzed	2 participants	2 participants
		-3.5 (0.71)	-8.5 (19.09)
CRT Phase: Change at Day 1	Number Analyzed	331 participants	322 participants
		0.7 (11.70)	1.3 (10.92)
CRT Phase: Change at Day 8	Number Analyzed	323 participants	315 participants
		1.5 (13.15)	2.2 (12.42)
CRT Phase: Change at Day 22	Number Analyzed	314 participants	309 participants
		0.5 (13.86)	2.6 (12.24)
CRT Phase: Change at Day 25	Number Analyzed	310 participants	306 participants
		-1.6 (14.87)	-1.2 (13.90)
CRT Phase: Change at Day 29	Number Analyzed	10 participants	8 participants
		-11.0 (20.47)	3.6 (21.29)
CRT Phase: Change at Day 39	Number Analyzed	310 participants	301 participants
		4.0 (15.46)	4.3 (14.71)
CRT Phase: Change at Day 43	Number Analyzed	293 participants	283 participants
		4.7 (16.82)	6.1 (14.78)
Maintenance Phase: Change at Cycle1/Day 1	Number Analyzed	282 participants	291 participants
		5.1 (16.23)	7.5 (14.43)
Maintenance Phase: Change at Cycle1/Day 15	Number Analyzed	265 participants	279 participants
		3.8 (15.04)	6.3 (13.65)
Maintenance Phase: Change at Cycle2/Day 1	Number Analyzed	266 participants	277 participants
		3.5 (15.30)	5.9 (14.74)
Maintenance Phase: Change at Cycle2/Day 15	Number Analyzed	254 participants	272 participants
		4.1 (15.32)	4.9 (13.94)
Maintenance Phase: Change at Cycle3/Day 1	Number Analyzed	249 participants	262 participants
		3.5 (14.49)	3.9 (14.37)
Maintenance Phase: Change at Cycle3/Day 15	Number Analyzed	234 participants	255 participants
		2.8 (14.73)	2.8 (14.14)
Maintenance Phase: Change at Cycle4/Day 1	Number Analyzed	222 participants	247 participants
		1.8 (14.79)	3.8 (14.95)
Maintenance Phase: Change at Cycle4/Day 15	Number Analyzed	216 participants	240 participants
		1.6 (14.80)	3.8 (15.02)
Maintenance Phase: Change at Cycle5/Day 1	Number Analyzed	210 participants	241 participants
		2.6 (13.88)	2.9 (14.82)
Maintenance Phase: Change at Cycle5/Day 15	Number Analyzed	204 participants	232 participants
		1.6 (15.11)	3.3 (13.74)
Maintenance Phase: Change at Cycle6/Day 1	Number Analyzed	201 participants	226 participants
		1.6 (15.42)	2.7 (15.72)
Maintenance Phase: Change at Cycle6/Day 15	Number Analyzed	198 participants	230 participants
		0.4 (14.04)	1.4 (13.66)
Maintenance Phase: Change at Cycle7/Day 1	Number Analyzed	190 participants	220 participants
		-0.1 (14.47)	2.5 (14.18)
Maintenance Phase: Change at Cycle7/Day 15	Number Analyzed	185 participants	214 participants
		-0.1 (14.24)	1.4 (14.33)
Maintenance Phase: Change at Cycle8/Day 1	Number Analyzed	173 participants	209 participants
		-0.2 (13.84)	1.0 (13.67)
Maintenance Phase: Change at Cycle8/Day 15	Number Analyzed	167 participants	194 participants
		-1.5 (14.52)	1.5 (14.86)
Maintenance Phase: Change at Cycle9/Day 1	Number Analyzed	169 participants	198 participants
		-1.0 (14.29)	-0.1 (14.06)
Maintenance Phase: Change at Cycle9/Day 15	Number Analyzed	162 participants	194 participants
		-1.0 (14.20)	0.2 (14.44)
Maintenance Phase: Change at Cycle10/Day 1	Number Analyzed	161 participants	192 participants
		-0.9 (13.40)	0.7 (14.52)
Maintenance Phase: Change at Cycle10/Day 15	Number Analyzed	159 participants	191 participants
		-0.5 (15.33)	0.7 (14.66)
Maintenance Phase: Change at Cycle11/Day 1	Number Analyzed	145 participants	178 participants
		-1.6 (14.57)	0.2 (14.01)
Maintenance Phase: Change at Cycle11/Day 15	Number Analyzed	139 participants	162 participants
		-0.2 (13.23)	0.3 (12.93)
Maintenance Phase: Change at Cycle12/Day 1	Number Analyzed	125 participants	156 participants
		-0.3 (13.92)	0.4 (13.67)
Maintenance Phase: Change at Cycle12/Day 15	Number Analyzed	115 participants	146 participants
		-1.4 (14.92)	-0.5 (12.47)
Maintenance Phase: Change at Cycle13/Day 1	Number Analyzed	105 participants	132 participants
		-1.4 (14.09)	-0.1 (12.22)
Maintenance Phase: Change at Cycle13/Day 15	Number Analyzed	92 participants	118 participants
		-1.3 (15.57)	0.4 (13.24)
EOT	Number Analyzed	223 participants	210 participants
		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.
Overall Number of Participants Analyzed		334	333
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	334 participants	333 participants
		0.7718 (0.17822)	0.7615 (0.18517)
CRT Phase: Change at Day 1	Number Analyzed	321 participants	318 participants
		-0.0078 (0.13269)	0.0176 (0.14066)
CRT Phase: Change at Day 29	Number Analyzed	293 participants	276 participants
		-0.0915 (0.22053)	-0.0487 (0.19175)
Maintenance Phase: Change at Cycle1/Day1	Number Analyzed	272 participants	279 participants
		-0.0749 (0.22126)	-0.0519 (0.17253)
Maintenance Phase: Change at Cycle3/Day1	Number Analyzed	239 participants	243 participants
		-0.0203 (0.21340)	-0.0160 (0.18179)
Maintenance Phase: Change at Cycle7/Day1	Number Analyzed	95 participants	113 participants
		0.0088 (0.16690)	0.0140 (0.16240)
Maintenance Phase: Change at Cycle7/Day15	Number Analyzed	59 participants	79 participants
		0.0552 (0.18544)	0.0472 (0.17990)
Maintenance Phase: Change at Cycle11/Day1	Number Analyzed	90 participants	111 participants
		0.0376 (0.21078)	0.0792 (0.19287)
Maintenance Phase: Change at Cycle11/Day15	Number Analyzed	36 participants	40 participants
		0.0673 (0.17227)	0.0389 (0.18732)
Maintenance Phase: Change at End of treatment	Number Analyzed	184 participants	187 participants
		-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.
Overall Number of Participants Analyzed		333	330
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	333 participants	330 participants
		75.8 (18.20)	74.9 (18.24)
CRT Phase: Change at Day 1	Number Analyzed	317 participants	314 participants
		-1.1 (13.49)	-1.4 (11.39)
CRT Phase: Change at Day 29	Number Analyzed	291 participants	271 participants
		-10.9 (19.94)	-9.2 (18.70)
Maintenance Phase: Change at Cycle1/Day1	Number Analyzed	272 participants	277 participants
		-7.7 (19.05)	-6.2 (18.67)
Maintenance Phase: Change at Cycle3/Day1	Number Analyzed	240 participants	236 participants
		-1.8 (18.00)	-0.7 (16.14)
Maintenance Phase: Change at Cycle7/Day1	Number Analyzed	95 participants	113 participants
		-0.6 (14.91)	8.6 (81.42)
Maintenance Phase: Change at Cycle7/Day15	Number Analyzed	59 participants	78 participants
		4.8 (18.52)	3.1 (19.28)
Maintenance Phase: Change at Cycle11/Day1	Number Analyzed	89 participants	108 participants
		0.3 (17.60)	4.3 (16.10)
Maintenance Phase: Change at Cycle11/Day15	Number Analyzed	37 participants	40 participants
		10.1 (24.69)	2.4 (18.20)
Maintenance Phase: Change at End of treatment	Number Analyzed	183 participants	184 participants
		-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.
Overall Number of Participants Analyzed		333	331
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	333 participants	331 participants
		60.56 (13.731)	61.05 (13.155)
CRT Phase: Change at Day 1	Number Analyzed	318 participants	317 participants
		-0.59 (8.719)	-0.14 (9.136)
CRT Phase: Change at Day 29	Number Analyzed	294 participants	275 participants
		-14.34 (16.847)	-14.56 (15.470)
CRT Phase: Change at Cycle1/Day1	Number Analyzed	272 participants	281 participants
		-11.33 (16.054)	-12.08 (14.950)
CRT Phase: Change at Cycle3/Day1	Number Analyzed	241 participants	241 participants
		-3.81 (14.017)	-2.26 (13.625)
CRT Phase: Change at Cycle7/Day1	Number Analyzed	96 participants	113 participants
		-0.86 (12.503)	-0.51 (14.585)
CRT Phase: Change at Cycle7/Day15	Number Analyzed	61 participants	78 participants
		3.96 (14.035)	0.92 (14.454)
CRT Phase: Change at Cycle11/Day1	Number Analyzed	88 participants	110 participants
		2.68 (13.367)	4.90 (14.207)
CRT Phase: Change at Cycle11/Day15	Number Analyzed	37 participants	40 participants
		3.96 (14.322)	3.37 (12.689)
CRT Phase: Change at End of treatment	Number Analyzed	184 participants	187 participants
		-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.
Overall Number of Participants Analyzed	299	307
Mean (Standard Deviation); Unit of Measure: % of PD-L1+ cells
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.
Overall Number of Participants Analyzed	289	294
Mean (Standard Deviation); Unit of Measure: % 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.
Overall Number of Participants Analyzed	14	15
Measure Type: Number; Unit of Measure: percentage of participants
Negative Pathology	7.14	26.70
Positive pathology	71.43	40.00
Pathology not reported	21.43	33.30

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.
Overall Number of Participants Analyzed		236
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram per milliliter
Lead-in/Day 1	Number Analyzed	236 participants
		203.6; (31%)
CRT/Day 8	Number Analyzed	207 participants
		190.9; (66%)
CRT/Day 25	Number Analyzed	189 participants
		162.4; (114%)
Cycle 1 Day 1	Number Analyzed	152 participants
		142; (117%)
Cycle 2 Day 1	Number Analyzed	128 participants
		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.
Overall Number of Participants Analyzed		267
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram per milliliter
Lead-in/Day 1	Number Analyzed	263 participants
		2.988; (1590%)
CRT/Day 8	Number Analyzed	267 participants
		11.9; (63%)
CRT/Day 25	Number Analyzed	251 participants
		6.284; (138%)
Cycle 1/Day 1	Number Analyzed	183 participants
		2.354; (131%)
Cycle 2/Day 1	Number Analyzed	198 participants
		17.56; (70%)
Cycle 5/Day 1	Number Analyzed	147 participants
		24.35; (66%)
Cycle 8/Day 1	Number Analyzed	125 participants
		29.59; (69%)
Cycle 11/Day 1	Number Analyzed	113 participants
		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.
Overall Number of Participants Analyzed	12	23
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram per milliliter per milligram
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.
Overall Number of Participants Analyzed	10	20
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram*hour/milliliter/milligram
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.
Overall Number of Participants Analyzed	12	23
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram per milliliter
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.
Overall Number of Participants Analyzed	12	23
Median (Full Range); Unit of Measure: hour
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)

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.
Overall Number of Participants Analyzed	331
Measure Type: Count of Participants; Unit of Measure: Participants
ADA never-positive	277 83.7%
ADA ever-positive	54 16.3%

25. Secondary Outcome

Title	Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status
Description	[Not Specified]
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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

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 (%)	Affected / at Risk (%)
Total	86/348 (24.71%)	62/344 (18.02%)
Serious Adverse Events
	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
	Affected / at Risk (%)	Affected / at Risk (%)
Total	184/348 (52.87%)	177/344 (51.45%)
Blood and lymphatic system disorders
Anaemia * 1	8/348 (2.30%)	12/344 (3.49%)
Bone marrow failure * 1	2/348 (0.57%)	1/344 (0.29%)
Febrile neutropenia * 1	9/348 (2.59%)	5/344 (1.45%)
Leukopenia * 1	1/348 (0.29%)	0/344 (0.00%)
Lymphadenopathy * 1	0/348 (0.00%)	1/344 (0.29%)
Neutropenia * 1	5/348 (1.44%)	3/344 (0.87%)
Splenic haematoma * 1	1/348 (0.29%)	0/344 (0.00%)
Thrombocytopenia * 1	1/348 (0.29%)	0/344 (0.00%)
Cardiac disorders
Acute coronary syndrome * 1	1/348 (0.29%)	0/344 (0.00%)
Acute myocardial infarction * 1	1/348 (0.29%)	1/344 (0.29%)
Angina pectoris * 1	0/348 (0.00%)	1/344 (0.29%)
Atrial fibrillation * 1	0/348 (0.00%)	1/344 (0.29%)
Bradycardia * 1	1/348 (0.29%)	2/344 (0.58%)
Cardiac arrest * 1	1/348 (0.29%)	0/344 (0.00%)
Cardiac failure * 1	1/348 (0.29%)	2/344 (0.58%)
Cardiac failure congestive * 1	1/348 (0.29%)	0/344 (0.00%)
Cardio-respiratory arrest * 1	1/348 (0.29%)	0/344 (0.00%)
Sinus tachycardia * 1	0/348 (0.00%)	1/344 (0.29%)
Supraventricular tachycardia * 1	2/348 (0.57%)	0/344 (0.00%)
Tachycardia * 1	0/348 (0.00%)	1/344 (0.29%)
Ear and labyrinth disorders
Deafness * 1	1/348 (0.29%)	0/344 (0.00%)
Tinnitus * 1	0/348 (0.00%)	1/344 (0.29%)
Vertigo * 1	1/348 (0.29%)	0/344 (0.00%)
Endocrine disorders
Adrenal insufficiency * 1	0/348 (0.00%)	1/344 (0.29%)
Hyperthyroidism * 1	0/348 (0.00%)	1/344 (0.29%)
Eye disorders
Pterygium * 1	0/348 (0.00%)	1/344 (0.29%)
Retinal detachment * 1	0/348 (0.00%)	1/344 (0.29%)
Gastrointestinal disorders
Abdominal pain * 1	0/348 (0.00%)	2/344 (0.58%)
Colitis * 1	1/348 (0.29%)	2/344 (0.58%)
Constipation * 1	1/348 (0.29%)	1/344 (0.29%)
Diarrhoea * 1	1/348 (0.29%)	2/344 (0.58%)
Dry mouth * 1	0/348 (0.00%)	1/344 (0.29%)
Duodenal ulcer perforation * 1	1/348 (0.29%)	0/344 (0.00%)
Dyspepsia * 1	1/348 (0.29%)	0/344 (0.00%)
Dysphagia * 1	15/348 (4.31%)	13/344 (3.78%)
Faecaloma * 1	0/348 (0.00%)	1/344 (0.29%)
Gastric perforation * 1	1/348 (0.29%)	1/344 (0.29%)
Haematemesis * 1	1/348 (0.29%)	1/344 (0.29%)
Haematochezia * 1	1/348 (0.29%)	0/344 (0.00%)
Large intestinal obstruction * 1	0/348 (0.00%)	1/344 (0.29%)
Mouth haemorrhage * 1	2/348 (0.57%)	2/344 (0.58%)
Mouth swelling * 1	0/348 (0.00%)	1/344 (0.29%)
Nausea * 1	7/348 (2.01%)	9/344 (2.62%)
Odynophagia * 1	3/348 (0.86%)	1/344 (0.29%)
Oesophageal obstruction * 1	1/348 (0.29%)	0/344 (0.00%)
Oesophagitis * 1	1/348 (0.29%)	1/344 (0.29%)
Oral pain * 1	1/348 (0.29%)	2/344 (0.58%)
Pneumoperitoneum * 1	1/348 (0.29%)	0/344 (0.00%)
Salivary hypersecretion * 1	1/348 (0.29%)	0/344 (0.00%)
Stomatitis * 1	7/348 (2.01%)	4/344 (1.16%)
Tongue haemorrhage * 1	2/348 (0.57%)	0/344 (0.00%)
Tongue ulceration * 1	1/348 (0.29%)	0/344 (0.00%)
Upper gastrointestinal haemorrhage * 1	1/348 (0.29%)	0/344 (0.00%)
Vomiting * 1	11/348 (3.16%)	13/344 (3.78%)
General disorders
Asthenia * 1	2/348 (0.57%)	6/344 (1.74%)
Chest pain * 1	2/348 (0.57%)	1/344 (0.29%)
Chills * 1	2/348 (0.57%)	0/344 (0.00%)
Condition aggravated * 1	1/348 (0.29%)	0/344 (0.00%)
Death * 1	2/348 (0.57%)	1/344 (0.29%)
Disease progression * 1	1/348 (0.29%)	1/344 (0.29%)
Fatigue * 1	2/348 (0.57%)	2/344 (0.58%)
General physical health deterioration * 1	1/348 (0.29%)	6/344 (1.74%)
Hyperpyrexia * 1	1/348 (0.29%)	0/344 (0.00%)
Hyperthermia * 1	0/348 (0.00%)	2/344 (0.58%)
Hypothermia * 1	0/348 (0.00%)	1/344 (0.29%)
Ill-defined disorder * 1	0/348 (0.00%)	1/344 (0.29%)
Malaise * 1	0/348 (0.00%)	1/344 (0.29%)
Mucosal inflammation * 1	5/348 (1.44%)	6/344 (1.74%)
Pain * 1	0/348 (0.00%)	2/344 (0.58%)
Performance status decreased * 1	0/348 (0.00%)	1/344 (0.29%)
Pyrexia * 1	12/348 (3.45%)	3/344 (0.87%)
Sudden death * 1	0/348 (0.00%)	1/344 (0.29%)
Swelling * 1	1/348 (0.29%)	0/344 (0.00%)
Hepatobiliary disorders
Cholelithiasis * 1	0/348 (0.00%)	1/344 (0.29%)
Hepatitis * 1	1/348 (0.29%)	0/344 (0.00%)
Hepatotoxicity * 1	1/348 (0.29%)	0/344 (0.00%)
Infections and infestations
Abdominal abscess * 1	1/348 (0.29%)	0/344 (0.00%)
Abscess oral * 1	0/348 (0.00%)	1/344 (0.29%)
Anal abscess * 1	0/348 (0.00%)	1/344 (0.29%)
Appendicitis * 1	0/348 (0.00%)	1/344 (0.29%)
Bacterial infection * 1	0/348 (0.00%)	1/344 (0.29%)
Bronchitis * 1	1/348 (0.29%)	1/344 (0.29%)
Bronchitis bacterial * 1	1/348 (0.29%)	0/344 (0.00%)
Candida infection * 1	1/348 (0.29%)	0/344 (0.00%)
Cellulitis * 1	3/348 (0.86%)	2/344 (0.58%)
Device related infection * 1	2/348 (0.57%)	1/344 (0.29%)
Device related sepsis * 1	1/348 (0.29%)	0/344 (0.00%)
Endocarditis * 1	0/348 (0.00%)	1/344 (0.29%)
Endocarditis candida * 1	1/348 (0.29%)	0/344 (0.00%)
Enterocolitis infectious * 1	2/348 (0.57%)	0/344 (0.00%)
Epididymitis * 1	1/348 (0.29%)	0/344 (0.00%)
Epiglottitis * 1	1/348 (0.29%)	0/344 (0.00%)
Herpes zoster * 1	1/348 (0.29%)	0/344 (0.00%)
Infection * 1	1/348 (0.29%)	3/344 (0.87%)
Infectious pleural effusion * 1	0/348 (0.00%)	1/344 (0.29%)
Localised infection * 1	1/348 (0.29%)	0/344 (0.00%)
Lower respiratory tract infection * 1	2/348 (0.57%)	2/344 (0.58%)
Lower respiratory tract infection bacterial * 1	0/348 (0.00%)	1/344 (0.29%)
Lung abscess * 1	1/348 (0.29%)	0/344 (0.00%)
Neutropenic infection * 1	1/348 (0.29%)	0/344 (0.00%)
Neutropenic sepsis * 1	1/348 (0.29%)	0/344 (0.00%)
Oesophageal candidiasis * 1	1/348 (0.29%)	0/344 (0.00%)
Oral candidiasis * 1	0/348 (0.00%)	1/344 (0.29%)
Oral infection * 1	0/348 (0.00%)	1/344 (0.29%)
Parotitis * 1	2/348 (0.57%)	1/344 (0.29%)
Pharyngitis * 1	0/348 (0.00%)	2/344 (0.58%)
Pneumococcal sepsis * 1	1/348 (0.29%)	0/344 (0.00%)
Pneumonia * 1	25/348 (7.18%)	20/344 (5.81%)
Pneumonia bacterial * 1	2/348 (0.57%)	0/344 (0.00%)
Respiratory tract infection * 1	4/348 (1.15%)	0/344 (0.00%)
Sepsis * 1	7/348 (2.01%)	5/344 (1.45%)
Sinusitis * 1	1/348 (0.29%)	0/344 (0.00%)
Skin infection * 1	1/348 (0.29%)	0/344 (0.00%)
Soft tissue infection * 1	1/348 (0.29%)	1/344 (0.29%)
Staphylococcal sepsis * 1	1/348 (0.29%)	0/344 (0.00%)
Stoma site abscess * 1	1/348 (0.29%)	0/344 (0.00%)
Stoma site infection * 1	1/348 (0.29%)	1/344 (0.29%)
Urinary tract infection * 1	2/348 (0.57%)	1/344 (0.29%)
Vascular device infection * 1	1/348 (0.29%)	0/344 (0.00%)
Osteomyelitis * 1	0/348 (0.00%)	1/344 (0.29%)
Injury, poisoning and procedural complications
Femoral neck fracture * 1	1/348 (0.29%)	0/344 (0.00%)
Femur fracture * 1	1/348 (0.29%)	0/344 (0.00%)
Gastrostomy failure * 1	1/348 (0.29%)	0/344 (0.00%)
Infusion related reaction * 1	2/348 (0.57%)	0/344 (0.00%)
Nerve injury * 1	0/348 (0.00%)	1/344 (0.29%)
Overdose * 1	1/348 (0.29%)	0/344 (0.00%)
Pancreatic injury * 1	0/348 (0.00%)	1/344 (0.29%)
Post procedural fever * 1	1/348 (0.29%)	0/344 (0.00%)
Post procedural haemorrhage * 1	2/348 (0.57%)	1/344 (0.29%)
Radiation associated pain * 1	0/348 (0.00%)	1/344 (0.29%)
Radiation fibrosis * 1	1/348 (0.29%)	0/344 (0.00%)
Radiation injury * 1	0/348 (0.00%)	1/344 (0.29%)
Radiation mucositis * 1	0/348 (0.00%)	2/344 (0.58%)
Radiation necrosis * 1	0/348 (0.00%)	1/344 (0.29%)
Radiation skin injury * 1	3/348 (0.86%)	2/344 (0.58%)
Stoma site inflammation * 1	0/348 (0.00%)	1/344 (0.29%)
Stoma site pain * 1	0/348 (0.00%)	1/344 (0.29%)
Subdural haemorrhage * 1	1/348 (0.29%)	0/344 (0.00%)
Thermal burn * 1	0/348 (0.00%)	1/344 (0.29%)
Tracheal haemorrhage * 1	2/348 (0.57%)	0/344 (0.00%)
Tracheal obstruction * 1	1/348 (0.29%)	0/344 (0.00%)
Osteoradionecrosis * 1	0/348 (0.00%)	1/344 (0.29%)
Investigations
Alanine aminotransferase increased * 1	1/348 (0.29%)	0/344 (0.00%)
Blood creatinine increased * 1	7/348 (2.01%)	6/344 (1.74%)
C-reactive protein increased * 1	0/348 (0.00%)	1/344 (0.29%)
Eastern Cooperative Oncology Group performance status worsened * 1	0/348 (0.00%)	1/344 (0.29%)
Hepatic enzyme increased * 1	1/348 (0.29%)	0/344 (0.00%)
Liver function test abnormal * 1	0/348 (0.00%)	1/344 (0.29%)
Liver function test increased * 1	1/348 (0.29%)	0/344 (0.00%)
Lymphocyte count decreased * 1	0/348 (0.00%)	1/344 (0.29%)
Neutrophil count decreased * 1	4/348 (1.15%)	1/344 (0.29%)
Oxygen saturation decreased * 1	1/348 (0.29%)	0/344 (0.00%)
Weight decreased * 1	6/348 (1.72%)	3/344 (0.87%)
White blood cell count decreased * 1	0/348 (0.00%)	1/344 (0.29%)
Metabolism and nutrition disorders
Adult failure to thrive * 1	0/348 (0.00%)	1/344 (0.29%)
Cachexia * 1	2/348 (0.57%)	2/344 (0.58%)
Decreased appetite * 1	5/348 (1.44%)	3/344 (0.87%)
Dehydration * 1	9/348 (2.59%)	15/344 (4.36%)
Diabetes mellitus inadequate control * 1	1/348 (0.29%)	0/344 (0.00%)
Diabetic ketoacidosis * 1	0/348 (0.00%)	1/344 (0.29%)
Electrolyte imbalance * 1	1/348 (0.29%)	0/344 (0.00%)
Failure to thrive * 1	2/348 (0.57%)	1/344 (0.29%)
Fluid overload * 1	1/348 (0.29%)	0/344 (0.00%)
Hypercalcaemia * 1	1/348 (0.29%)	1/344 (0.29%)
Hyperglycaemia * 1	2/348 (0.57%)	0/344 (0.00%)
Hyperglycaemic hyperosmolar nonketotic syndrome * 1	1/348 (0.29%)	0/344 (0.00%)
Hypoalbuminaemia * 1	0/348 (0.00%)	1/344 (0.29%)
Hypocalcaemia * 1	0/348 (0.00%)	2/344 (0.58%)
Hypoglycaemia * 1	0/348 (0.00%)	1/344 (0.29%)
Hypokalaemia * 1	4/348 (1.15%)	3/344 (0.87%)
Hyponatraemia * 1	4/348 (1.15%)	7/344 (2.03%)
Hypophagia * 1	1/348 (0.29%)	0/344 (0.00%)
Ketoacidosis * 1	0/348 (0.00%)	1/344 (0.29%)
Malnutrition * 1	2/348 (0.57%)	3/344 (0.87%)
Metabolic disorder * 1	0/348 (0.00%)	1/344 (0.29%)
Musculoskeletal and connective tissue disorders
Arthritis * 1	1/348 (0.29%)	0/344 (0.00%)
Back pain * 1	0/348 (0.00%)	1/344 (0.29%)
Haematoma muscle * 1	0/348 (0.00%)	1/344 (0.29%)
Neck pain * 1	1/348 (0.29%)	1/344 (0.29%)
Oligoarthritis * 1	1/348 (0.29%)	0/344 (0.00%)
Osteonecrosis of jaw * 1	0/348 (0.00%)	1/344 (0.29%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma * 1	0/348 (0.00%)	1/344 (0.29%)
Non-small cell lung cancer * 1	1/348 (0.29%)	0/344 (0.00%)
Oesophageal carcinoma * 1	0/348 (0.00%)	1/344 (0.29%)
Oesophageal neoplasm * 1	1/348 (0.29%)	0/344 (0.00%)
Plasmacytoma * 1	0/348 (0.00%)	1/344 (0.29%)
Transitional cell cancer of the renal pelvis and ureter * 1	1/348 (0.29%)	0/344 (0.00%)
Tumour haemorrhage * 1	4/348 (1.15%)	4/344 (1.16%)
Nervous system disorders
Brain hypoxia * 1	1/348 (0.29%)	0/344 (0.00%)
Cerebral ischaemia * 1	0/348 (0.00%)	1/344 (0.29%)
Cerebrovascular accident * 1	1/348 (0.29%)	1/344 (0.29%)
Coma * 1	1/348 (0.29%)	0/344 (0.00%)
Depressed level of consciousness * 1	0/348 (0.00%)	1/344 (0.29%)
Dizziness * 1	0/348 (0.00%)	1/344 (0.29%)
Epilepsy * 1	1/348 (0.29%)	1/344 (0.29%)
Headache * 1	1/348 (0.29%)	0/344 (0.00%)
Presyncope * 1	0/348 (0.00%)	1/344 (0.29%)
Seizure * 1	0/348 (0.00%)	1/344 (0.29%)
Subacute combined cord degeneration * 1	0/348 (0.00%)	1/344 (0.29%)
Syncope * 1	2/348 (0.57%)	0/344 (0.00%)
Product Issues
Device dislocation * 1	1/348 (0.29%)	3/344 (0.87%)
Device malfunction * 1	1/348 (0.29%)	0/344 (0.00%)
Embedded device * 1	0/348 (0.00%)	1/344 (0.29%)
Psychiatric disorders
Confusional state * 1	3/348 (0.86%)	0/344 (0.00%)
Delirium * 1	1/348 (0.29%)	1/344 (0.29%)
Suicidal ideation * 1	0/348 (0.00%)	1/344 (0.29%)
Suicide attempt * 1	0/348 (0.00%)	1/344 (0.29%)
Renal and urinary disorders
Acute kidney injury * 1	12/348 (3.45%)	11/344 (3.20%)
Hydronephrosis * 1	1/348 (0.29%)	0/344 (0.00%)
Nephritis * 1	1/348 (0.29%)	0/344 (0.00%)
Oliguria * 1	0/348 (0.00%)	1/344 (0.29%)
Renal disorder * 1	1/348 (0.29%)	0/344 (0.00%)
Renal failure * 1	0/348 (0.00%)	4/344 (1.16%)
Renal tubular necrosis * 1	1/348 (0.29%)	0/344 (0.00%)
Urinary retention * 1	0/348 (0.00%)	1/344 (0.29%)
Reproductive system and breast disorders
Scrotal oedema * 1	0/348 (0.00%)	1/344 (0.29%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome * 1	1/348 (0.29%)	0/344 (0.00%)
Acute respiratory failure * 1	2/348 (0.57%)	1/344 (0.29%)
Asphyxia * 1	1/348 (0.29%)	2/344 (0.58%)
Aspiration * 1	1/348 (0.29%)	1/344 (0.29%)
Atelectasis * 1	0/348 (0.00%)	1/344 (0.29%)
Chronic obstructive pulmonary disease * 1	0/348 (0.00%)	1/344 (0.29%)
Cough * 1	0/348 (0.00%)	1/344 (0.29%)
Dyspnoea * 1	5/348 (1.44%)	7/344 (2.03%)
Haemoptysis * 1	2/348 (0.57%)	3/344 (0.87%)
Hypoxia * 1	1/348 (0.29%)	3/344 (0.87%)
Laryngeal haemorrhage * 1	0/348 (0.00%)	1/344 (0.29%)
Laryngeal inflammation * 1	2/348 (0.57%)	0/344 (0.00%)
Laryngeal necrosis * 1	0/348 (0.00%)	1/344 (0.29%)
Laryngeal oedema * 1	5/348 (1.44%)	4/344 (1.16%)
Laryngeal stenosis * 1	2/348 (0.57%)	0/344 (0.00%)
Obstructive airways disorder * 1	0/348 (0.00%)	1/344 (0.29%)
Oropharyngeal pain * 1	1/348 (0.29%)	2/344 (0.58%)
Pharyngeal haemorrhage * 1	2/348 (0.57%)	2/344 (0.58%)
Pharyngeal inflammation * 1	2/348 (0.57%)	0/344 (0.00%)
Pharyngeal necrosis * 1	1/348 (0.29%)	0/344 (0.00%)
Pharyngeal oedema * 1	1/348 (0.29%)	0/344 (0.00%)
Pharyngeal stenosis * 1	1/348 (0.29%)	0/344 (0.00%)
Pharyngeal ulceration * 1	2/348 (0.57%)	0/344 (0.00%)
Pneumonia aspiration * 1	5/348 (1.44%)	5/344 (1.45%)
Pneumonitis * 1	6/348 (1.72%)	1/344 (0.29%)
Pneumothorax * 1	1/348 (0.29%)	2/344 (0.58%)
Productive cough * 1	1/348 (0.29%)	1/344 (0.29%)
Pulmonary embolism * 1	2/348 (0.57%)	0/344 (0.00%)
Respiratory arrest * 1	0/348 (0.00%)	1/344 (0.29%)
Respiratory distress * 1	2/348 (0.57%)	1/344 (0.29%)
Respiratory failure * 1	0/348 (0.00%)	2/344 (0.58%)
Respiratory tract oedema * 1	1/348 (0.29%)	0/344 (0.00%)
Stridor * 1	1/348 (0.29%)	1/344 (0.29%)
Tonsillar haemorrhage * 1	1/348 (0.29%)	0/344 (0.00%)
Tracheal stenosis * 1	1/348 (0.29%)	1/344 (0.29%)
Skin and subcutaneous tissue disorders
Erythema multiforme * 1	1/348 (0.29%)	0/344 (0.00%)
Rash * 1	1/348 (0.29%)	0/344 (0.00%)
Surgical and medical procedures
Gastrostomy * 1	1/348 (0.29%)	0/344 (0.00%)
Vascular disorders
Capillary leak syndrome * 1	0/348 (0.00%)	1/344 (0.29%)
Circulatory collapse * 1	0/348 (0.00%)	1/344 (0.29%)
Embolism * 1	1/348 (0.29%)	0/344 (0.00%)
Haematoma * 1	0/348 (0.00%)	1/344 (0.29%)
Haemorrhage * 1	1/348 (0.29%)	1/344 (0.29%)
Hypotension * 1	2/348 (0.57%)	4/344 (1.16%)
Lymphorrhoea * 1	0/348 (0.00%)	1/344 (0.29%)
Phlebitis superficial * 1	1/348 (0.29%)	0/344 (0.00%)
Shock * 1	1/348 (0.29%)	0/344 (0.00%)
Vascular rupture * 1	1/348 (0.29%)	0/344 (0.00%)
Vasculitis * 1	1/348 (0.29%)	0/344 (0.00%)
Venous haemorrhage * 1	0/348 (0.00%)	1/344 (0.29%)
1 Term from vocabulary, MedDRA Version 23.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Avelumab + Standard of Care Chemotherapy (SOC CRT)	Placebo + SOC CRT
	Affected / at Risk (%)	Affected / at Risk (%)
Total	344/348 (98.85%)	340/344 (98.84%)
Blood and lymphatic system disorders
Anaemia * 1	206/348 (59.20%)	192/344 (55.81%)
Leukopenia * 1	64/348 (18.39%)	46/344 (13.37%)
Lymphopenia * 1	33/348 (9.48%)	27/344 (7.85%)
Neutropenia * 1	102/348 (29.31%)	98/344 (28.49%)
Thrombocytopenia * 1	45/348 (12.93%)	41/344 (11.92%)
Ear and labyrinth disorders
Ear pain * 1	23/348 (6.61%)	12/344 (3.49%)
Hypoacusis * 1	29/348 (8.33%)	30/344 (8.72%)
Tinnitus * 1	59/348 (16.95%)	66/344 (19.19%)
Endocrine disorders
Hyperthyroidism * 1	24/348 (6.90%)	7/344 (2.03%)
Hypothyroidism * 1	51/348 (14.66%)	45/344 (13.08%)
Gastrointestinal disorders
Abdominal pain * 1	11/348 (3.16%)	20/344 (5.81%)
Abdominal pain upper * 1	14/348 (4.02%)	18/344 (5.23%)
Constipation * 1	178/348 (51.15%)	155/344 (45.06%)
Diarrhoea * 1	83/348 (23.85%)	66/344 (19.19%)
Dry mouth * 1	151/348 (43.39%)	158/344 (45.93%)
Dyspepsia * 1	23/348 (6.61%)	21/344 (6.10%)
Dysphagia * 1	143/348 (41.09%)	152/344 (44.19%)
Nausea * 1	210/348 (60.34%)	199/344 (57.85%)
Odynophagia * 1	62/348 (17.82%)	48/344 (13.95%)
Oral pain * 1	39/348 (11.21%)	43/344 (12.50%)
Stomatitis * 1	92/348 (26.44%)	96/344 (27.91%)
Vomiting * 1	112/348 (32.18%)	121/344 (35.17%)
General disorders
Asthenia * 1	63/348 (18.10%)	58/344 (16.86%)
Chills * 1	39/348 (11.21%)	7/344 (2.03%)
Fatigue * 1	116/348 (33.33%)	127/344 (36.92%)
Localised oedema * 1	22/348 (6.32%)	20/344 (5.81%)
Malaise * 1	20/348 (5.75%)	23/344 (6.69%)
Mucosal inflammation * 1	146/348 (41.95%)	131/344 (38.08%)
Oedema peripheral * 1	19/348 (5.46%)	16/344 (4.65%)
Pain * 1	23/348 (6.61%)	28/344 (8.14%)
Pyrexia * 1	87/348 (25.00%)	45/344 (13.08%)
Infections and infestations
Oral candidiasis * 1	25/348 (7.18%)	31/344 (9.01%)
Pneumonia * 1	36/348 (10.34%)	25/344 (7.27%)
Upper respiratory tract infection * 1	24/348 (6.90%)	21/344 (6.10%)
Injury, poisoning and procedural complications
Infusion related reaction * 1	24/348 (6.90%)	6/344 (1.74%)
Radiation skin injury * 1	135/348 (38.79%)	136/344 (39.53%)
Investigations
Alanine aminotransferase increased * 1	56/348 (16.09%)	30/344 (8.72%)
Amylase increased * 1	22/348 (6.32%)	10/344 (2.91%)
Aspartate aminotransferase increased * 1	55/348 (15.80%)	26/344 (7.56%)
Blood alkaline phosphatase increased * 1	22/348 (6.32%)	9/344 (2.62%)
Blood creatinine increased * 1	88/348 (25.29%)	73/344 (21.22%)
Blood urea increased * 1	18/348 (5.17%)	17/344 (4.94%)
Gamma-glutamyltransferase increased * 1	23/348 (6.61%)	15/344 (4.36%)
Lymphocyte count decreased * 1	40/348 (11.49%)	42/344 (12.21%)
Neutrophil count decreased * 1	64/348 (18.39%)	60/344 (17.44%)
Platelet count decreased * 1	40/348 (11.49%)	33/344 (9.59%)
Weight decreased * 1	157/348 (45.11%)	171/344 (49.71%)
White blood cell count decreased * 1	69/348 (19.83%)	64/344 (18.60%)
Metabolism and nutrition disorders
Decreased appetite * 1	128/348 (36.78%)	124/344 (36.05%)
Dehydration * 1	31/348 (8.91%)	29/344 (8.43%)
Hyperglycaemia * 1	31/348 (8.91%)	33/344 (9.59%)
Hyperkalaemia * 1	34/348 (9.77%)	32/344 (9.30%)
Hypoalbuminaemia * 1	42/348 (12.07%)	36/344 (10.47%)
Hypocalcaemia * 1	29/348 (8.33%)	23/344 (6.69%)
Hypokalaemia * 1	87/348 (25.00%)	71/344 (20.64%)
Hypomagnesaemia * 1	93/348 (26.72%)	84/344 (24.42%)
Hyponatraemia * 1	83/348 (23.85%)	68/344 (19.77%)
Hypophosphataemia * 1	23/348 (6.61%)	32/344 (9.30%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	17/348 (4.89%)	20/344 (5.81%)
Neck pain * 1	30/348 (8.62%)	25/344 (7.27%)
Nervous system disorders
Dizziness * 1	41/348 (11.78%)	33/344 (9.59%)
Dysgeusia * 1	106/348 (30.46%)	119/344 (34.59%)
Headache * 1	44/348 (12.64%)	41/344 (11.92%)
Neuropathy peripheral * 1	11/348 (3.16%)	28/344 (8.14%)
Psychiatric disorders
Anxiety * 1	26/348 (7.47%)	34/344 (9.88%)
Depression * 1	10/348 (2.87%)	18/344 (5.23%)
Insomnia * 1	57/348 (16.38%)	47/344 (13.66%)
Renal and urinary disorders
Acute kidney injury * 1	18/348 (5.17%)	22/344 (6.40%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	74/348 (21.26%)	63/344 (18.31%)
Dysphonia * 1	51/348 (14.66%)	47/344 (13.66%)
Dyspnoea * 1	33/348 (9.48%)	33/344 (9.59%)
Hiccups * 1	26/348 (7.47%)	23/344 (6.69%)
Oropharyngeal pain * 1	75/348 (21.55%)	92/344 (26.74%)
Pharyngeal inflammation * 1	24/348 (6.90%)	23/344 (6.69%)
Productive cough * 1	40/348 (11.49%)	31/344 (9.01%)
Skin and subcutaneous tissue disorders
Alopecia * 1	22/348 (6.32%)	20/344 (5.81%)
Dermatitis * 1	52/348 (14.94%)	42/344 (12.21%)
Dry skin * 1	18/348 (5.17%)	24/344 (6.98%)
Erythema * 1	24/348 (6.90%)	27/344 (7.85%)
Pruritus * 1	38/348 (10.92%)	24/344 (6.98%)
Rash * 1	43/348 (12.36%)	36/344 (10.47%)
Vascular disorders
Hypertension * 1	32/348 (9.20%)	28/344 (8.14%)
Hypotension * 1	22/348 (6.32%)	14/344 (4.07%)
Lymphoedema * 1	18/348 (5.17%)	15/344 (4.36%)
1 Term from vocabulary, MedDRA Version 23.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02952586
• Other Study ID Numbers: B9991016; 2016-001456-21 ( EudraCT Number ); LOCALLY ADVANCED HEAD AND NECK ( Other Identifier: Alias Study Number )
• First Submitted: October 31, 2016
• First Posted: November 2, 2016
• Results First Submitted: December 21, 2020
• Results First Posted: February 24, 2021
• Last Update Posted: September 22, 2021