Trial Outcomes & Findings for 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) (NCT NCT02952586)

Last Updated: 2021-09-22

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

697 participants

Primary outcome timeframe

From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months)

Results posted on

2021-09-22

Participant Flow

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

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.

Participant milestones

Participant milestones
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) 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.	Placebo + SOC CRT 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.
Lead-In Phase (7 Days) STARTED	350	347
Lead-In Phase (7 Days) Safety Analysis Set	348	344
Lead-In Phase (7 Days) COMPLETED	345	343
Lead-In Phase (7 Days) NOT COMPLETED	5	4
CRT for Avelumab or Placebo (63 Days) STARTED	345	340
CRT for Avelumab or Placebo (63 Days) COMPLETED	312	313
CRT for Avelumab or Placebo (63 Days) NOT COMPLETED	33	27
CRT for Cisplatin (63 Days) STARTED	345	340
CRT for Cisplatin (63 Days) COMPLETED	234	236
CRT for Cisplatin (63 Days) NOT COMPLETED	111	104
CRT for IMRT (63 Days) STARTED	345	340
CRT for IMRT (63 Days) COMPLETED	322	320
CRT for IMRT (63 Days) NOT COMPLETED	23	20
Maintenance Phase (12 Months) STARTED	291	304
Maintenance Phase (12 Months) COMPLETED	139	177
Maintenance Phase (12 Months) NOT COMPLETED	152	127
Follow-Up Phase (90 Days) STARTED	266	284
Follow-Up Phase (90 Days) COMPLETED	208	216
Follow-Up Phase (90 Days) NOT COMPLETED	58	68
LT Follow-up (up to 45 Months) STARTED	247	237
LT Follow-up (up to 45 Months) COMPLETED	0	0
LT Follow-up (up to 45 Months) NOT COMPLETED	247	237

Reasons for withdrawal

Reasons for withdrawal
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) 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.	Placebo + SOC CRT 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.
Lead-In Phase (7 Days) Death	0	1
Lead-In Phase (7 Days) Adverse Event	3	0
Lead-In Phase (7 Days) No Longer Met Eligibility Criteria	0	1
Lead-In Phase (7 Days) Withdrawal by Subject	2	2
CRT for Avelumab or Placebo (63 Days) Death	5	8
CRT for Avelumab or Placebo (63 Days) Adverse Event	12	12
CRT for Avelumab or Placebo (63 Days) Physician Decision	2	1
CRT for Avelumab or Placebo (63 Days) Global Deterioration of Health Status	1	0
CRT for Avelumab or Placebo (63 Days) Withdrawal by Subject	10	4
CRT for Avelumab or Placebo (63 Days) Lost to Follow-up	1	1
CRT for Avelumab or Placebo (63 Days) Other	2	1
CRT for Cisplatin (63 Days) Death	3	8
CRT for Cisplatin (63 Days) Adverse Event	82	81
CRT for Cisplatin (63 Days) Physician Decision	12	10
CRT for Cisplatin (63 Days) Global Deterioration of Health Status	1	0
CRT for Cisplatin (63 Days) Withdrawal by Subject	11	3
CRT for Cisplatin (63 Days) Lost to Follow-up	1	1
CRT for Cisplatin (63 Days) Other	1	1
CRT for IMRT (63 Days) Death	5	8
CRT for IMRT (63 Days) Adverse Event	5	5
CRT for IMRT (63 Days) Global Deterioration of Health Status	1	0
CRT for IMRT (63 Days) Withdrawal by Subject	10	6
CRT for IMRT (63 Days) Lost to Follow-up	1	1
CRT for IMRT (63 Days) Other	1	0
Maintenance Phase (12 Months) Death	17	11
Maintenance Phase (12 Months) Progressive disease	60	54
Maintenance Phase (12 Months) Adverse Event	24	21
Maintenance Phase (12 Months) Non-compliance With Study Drug	1	1
Maintenance Phase (12 Months) Physician Decision	1	1
Maintenance Phase (12 Months) Global Deterioration of Health Status	14	5
Maintenance Phase (12 Months) Withdrawal by Subject	31	25
Maintenance Phase (12 Months) Lost to Follow-up	1	2
Maintenance Phase (12 Months) Other	2	1
Maintenance Phase (12 Months) Study Terminated by Sponsor	1	6
Follow-Up Phase (90 Days) Death	12	10
Follow-Up Phase (90 Days) Withdrawal by Subject	6	2
Follow-Up Phase (90 Days) Lost to Follow-up	1	1
Follow-Up Phase (90 Days) Other	7	5
Follow-Up Phase (90 Days) Study Terminated by Sponsor	32	50
LT Follow-up (up to 45 Months) Death	51	31
LT Follow-up (up to 45 Months) Withdrawal by Subject	7	1
LT Follow-up (up to 45 Months) Lost to Follow-up	2	4
LT Follow-up (up to 45 Months) Study Terminated by Sponsor	187	201

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=350 Participants 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.	Placebo + SOC CRT n=347 Participants 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 n=697 Participants Total of all reporting groups
Age, Continuous	59.36 years STANDARD_DEVIATION 8.56 • n=5 Participants	58.88 years STANDARD_DEVIATION 9.09 • n=7 Participants	59.12 years STANDARD_DEVIATION 8.83 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	62 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Male	290 Participants n=5 Participants	285 Participants n=7 Participants	575 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	312 Participants n=5 Participants	312 Participants n=7 Participants	624 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	102 Participants n=5 Participants	86 Participants n=7 Participants	188 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	224 Participants n=5 Participants	229 Participants n=7 Participants	453 Participants n=5 Participants
Race/Ethnicity, Customized Other	14 Participants n=5 Participants	21 Participants n=7 Participants	35 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months)

Population: FAS included all randomized participants.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=350 Participants 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.	Placebo + SOC CRT n=347 Participants 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.
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator	NA months Interval 16.9 to 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.	NA months Interval 23.0 to 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.

SECONDARY outcome

Timeframe: From randomization to the date of death or censored date, whichever occurred first (up to 37 months)

Population: FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=350 Participants 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.	Placebo + SOC CRT n=347 Participants 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 Survival (OS)	NA months 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.	NA months 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.

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 37 months)

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

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=6 Participants 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.	Placebo + SOC CRT n=7 Participants 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.
Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site	0 percentage of participants Interval 0.0 to 45.9	14.3 percentage of participants Interval 0.4 to 57.9

SECONDARY outcome

Timeframe: From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months)

Population: FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=350 Participants 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.	Placebo + SOC CRT n=347 Participants 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.
Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator	NA months Interval 22.4 to 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.	NA months Interval 25.0 to 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.

SECONDARY outcome

Timeframe: From randomization until disease progression or death, whichever occurred first (up to 37 months)

Population: FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=350 Participants 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.	Placebo + SOC CRT n=347 Participants 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.
Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator	74.0 percentage of participants Interval 69.1 to 78.5	74.9 percentage of participants Interval 70.0 to 79.4

SECONDARY outcome

Timeframe: From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months)

Population: FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=350 Participants 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.	Placebo + SOC CRT n=347 Participants 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.
Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator	NA months Interval 22.8 to 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.	NA months 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.

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=259 Participants 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.	Placebo + SOC CRT n=260 Participants 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.
Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator	NA months 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.	NA months 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.

SECONDARY outcome

Timeframe: Baseline up to 44 months

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

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=348 Participants 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.	Placebo + SOC CRT n=344 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Grade 1	10 Participants	8 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Grade 2	30 Participants	53 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Grade 3	224 Participants	215 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Grade 4	59 Participants	49 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Grade 5	22 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline up to 15 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=346 Participants 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.	Placebo + SOC CRT n=340 Participants 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.
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypercalcemia: New or worsened to grade >=1	67 Participants	59 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypercalcemia: New or worsened to grade >=3	1 Participants	5 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Anemia: New or worsened to grade >=1	314 Participants	311 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Anemia: New or worsened to grade >=3	42 Participants	49 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Lymphocyte Count Decreased: New or worsened to grade >=1	336 Participants	330 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Lymphocyte Count (LC) Decreased: New or worsened to grade >=3	279 Participants	284 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Lymphocyte Count (LC) Increased: New or worsened to grade >=1	7 Participants	7 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Lymphocyte Count Increased: New or worsened to grade >=3	0 Participants	0 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Neutrophil Count (NC) Decreased: New or worsened to grade >=1	257 Participants	237 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Neutrophil Count Decreased: New or worsened to grade >=3	120 Participants	101 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Platelet Count (PC) Decreased : New or worsened to grade >=1	157 Participants	154 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Platelet Count Decreased: New or worsened to grade >=3	20 Participants	7 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters White Blood Cell (WBC) Decreased: New or worsened to grade >=1	309 Participants	307 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters White Blood Cell Decreased: New or worsened to grade >=3	121 Participants	129 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Alanine aminotransferase (ALT) increased: New or worsened to grade >=1	152 Participants	135 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters ALT increased: New or worsened to grade >=3	13 Participants	2 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Alkaline phosphatase increased (ALP): New or worsened to grade >=1	72 Participants	49 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Alkaline phosphatase increased: New or worsened to grade >=3	1 Participants	1 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Aspartate aminotransferase (AST) increased: New or worsened to grade >=1	146 Participants	111 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Aspartate aminotransferase increased: New or worsened to grade >=3	11 Participants	4 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Blood bilirubin (BB) increased (BB): New or worsened to grade >=1	58 Participants	54 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Blood bilirubin increased: New or worsened to grade >=3	9 Participants	4 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Cholesterol (CH) high: New or worsened to grade >=1	25 Participants	21 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Cholesterol high: New or worsened to grade >=3	0 Participants	0 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters CPK increased: New or worsened to grade >=1	7 Participants	7 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters CPK increased: New or worsened to grade >=3	0 Participants	1 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Creatinine increased: New or worsened to grade >=1	334 Participants	325 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Creatinine increased: New or worsened to grade >=3	36 Participants	37 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters GGT increased: New or worsened to grade >=1	37 Participants	23 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters GGT increased: New or worsened to grade >=3	10 Participants	5 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hyperglycemia: New or worsened to grade >=1	144 Participants	137 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hyperglycemia: New or worsened to grade >=3	28 Participants	29 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hyperkalemia: New or worsened to grade >=1	106 Participants	113 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hyperkalemia: New or worsened to grade >=3	9 Participants	17 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypermagnesemia: New or worsened to grade >=1	39 Participants	40 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypermagnesemia: New or worsened to grade >=3	10 Participants	10 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypernatremia: New or worsened to grade >=1	22 Participants	20 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypernatremia: New or worsened to grade >=3	1 Participants	0 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypertriglyceridemia: New or worsened to grade >=1	35 Participants	26 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypertriglyceridemia: New or worsened to grade >=3	1 Participants	2 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypoalbuminemia: New or worsened to grade >=1	195 Participants	170 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypoalbuminemia: New or worsened to grade >=3	7 Participants	5 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypocalcemia: New or worsened to grade >=1	82 Participants	88 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypocalcemia: New or worsened to grade >=3	8 Participants	14 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypoglycemia: New or worsened to grade >=1	56 Participants	44 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypoglycemia: New or worsened to grade >=3	2 Participants	2 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypokalemia: New or worsened to grade >=1	140 Participants	122 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypokalemia: New or worsened to grade >=3	55 Participants	49 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypomagnesemia: New or worsened to grade >=1	180 Participants	158 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypomagnesemia: New or worsened to grade >=3	8 Participants	12 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hyponatremia: New or worsened to grade >=1	232 Participants	212 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hyponatremia: New or worsened to grade >=3	74 Participants	70 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypophosphatemia: New or worsened to grade >=1	108 Participants	100 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Hypophosphatemia: New or worsened to grade >=3	21 Participants	19 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Lipase increased: New or worsened to grade >=1	19 Participants	13 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Lipase increased: New or worsened to grade >=3	11 Participants	3 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Serum amylase increased: New or worsened to grade >=1	13 Participants	10 Participants
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Serum amylase increased: New or worsened to grade >=3	9 Participants	5 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=342 Participants 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.	Placebo + SOC CRT n=336 Participants 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.
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle4/Day 1	1.8 beats per minute Standard Deviation 14.79	3.8 beats per minute Standard Deviation 14.95
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle4/Day 15	1.6 beats per minute Standard Deviation 14.80	3.8 beats per minute Standard Deviation 15.02
Change From Baseline in Vital Sign - Pulse Rate EOT	0.2 beats per minute Standard Deviation 14.73	1.9 beats per minute Standard Deviation 14.09
Change From Baseline in Vital Sign - Pulse Rate Baseline	79.9 beats per minute Standard Deviation 13.72	86.0 beats per minute Standard Deviation 43.0
Change From Baseline in Vital Sign - Pulse Rate Lead in Phase: Change at Day 1	-3.5 beats per minute Standard Deviation 0.71	-8.5 beats per minute Standard Deviation 19.09
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 1	0.7 beats per minute Standard Deviation 11.70	1.3 beats per minute Standard Deviation 10.92
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 8	1.5 beats per minute Standard Deviation 13.15	2.2 beats per minute Standard Deviation 12.42
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 22	0.5 beats per minute Standard Deviation 13.86	2.6 beats per minute Standard Deviation 12.24
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 25	-1.6 beats per minute Standard Deviation 14.87	-1.2 beats per minute Standard Deviation 13.90
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 29	-11.0 beats per minute Standard Deviation 20.47	3.6 beats per minute Standard Deviation 21.29
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 39	4.0 beats per minute Standard Deviation 15.46	4.3 beats per minute Standard Deviation 14.71
Change From Baseline in Vital Sign - Pulse Rate CRT Phase: Change at Day 43	4.7 beats per minute Standard Deviation 16.82	6.1 beats per minute Standard Deviation 14.78
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle1/Day 1	5.1 beats per minute Standard Deviation 16.23	7.5 beats per minute Standard Deviation 14.43
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle1/Day 15	3.8 beats per minute Standard Deviation 15.04	6.3 beats per minute Standard Deviation 13.65
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle2/Day 1	3.5 beats per minute Standard Deviation 15.30	5.9 beats per minute Standard Deviation 14.74
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle2/Day 15	4.1 beats per minute Standard Deviation 15.32	4.9 beats per minute Standard Deviation 13.94
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle3/Day 1	3.5 beats per minute Standard Deviation 14.49	3.9 beats per minute Standard Deviation 14.37
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle3/Day 15	2.8 beats per minute Standard Deviation 14.73	2.8 beats per minute Standard Deviation 14.14
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle5/Day 1	2.6 beats per minute Standard Deviation 13.88	2.9 beats per minute Standard Deviation 14.82
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle5/Day 15	1.6 beats per minute Standard Deviation 15.11	3.3 beats per minute Standard Deviation 13.74
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle6/Day 1	1.6 beats per minute Standard Deviation 15.42	2.7 beats per minute Standard Deviation 15.72
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle6/Day 15	0.4 beats per minute Standard Deviation 14.04	1.4 beats per minute Standard Deviation 13.66
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle7/Day 1	-0.1 beats per minute Standard Deviation 14.47	2.5 beats per minute Standard Deviation 14.18
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle7/Day 15	-0.1 beats per minute Standard Deviation 14.24	1.4 beats per minute Standard Deviation 14.33
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle8/Day 1	-0.2 beats per minute Standard Deviation 13.84	1.0 beats per minute Standard Deviation 13.67
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle8/Day 15	-1.5 beats per minute Standard Deviation 14.52	1.5 beats per minute Standard Deviation 14.86
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle9/Day 1	-1.0 beats per minute Standard Deviation 14.29	-0.1 beats per minute Standard Deviation 14.06
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle9/Day 15	-1.0 beats per minute Standard Deviation 14.20	0.2 beats per minute Standard Deviation 14.44
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle10/Day 1	-0.9 beats per minute Standard Deviation 13.40	0.7 beats per minute Standard Deviation 14.52
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle10/Day 15	-0.5 beats per minute Standard Deviation 15.33	0.7 beats per minute Standard Deviation 14.66
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle11/Day 1	-1.6 beats per minute Standard Deviation 14.57	0.2 beats per minute Standard Deviation 14.01
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle11/Day 15	-0.2 beats per minute Standard Deviation 13.23	0.3 beats per minute Standard Deviation 12.93
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle12/Day 1	-0.3 beats per minute Standard Deviation 13.92	0.4 beats per minute Standard Deviation 13.67
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle12/Day 15	-1.4 beats per minute Standard Deviation 14.92	-0.5 beats per minute Standard Deviation 12.47
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle13/Day 1	-1.4 beats per minute Standard Deviation 14.09	-0.1 beats per minute Standard Deviation 12.22
Change From Baseline in Vital Sign - Pulse Rate Maintenance Phase: Change at Cycle13/Day 15	-1.3 beats per minute Standard Deviation 15.57	0.4 beats per minute Standard Deviation 13.24

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=334 Participants 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.	Placebo + SOC CRT n=333 Participants 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.
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle7/Day15	0.0552 units on a scale Standard Deviation 0.18544	0.0472 units on a scale Standard Deviation 0.17990
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Baseline	0.7718 units on a scale Standard Deviation 0.17822	0.7615 units on a scale Standard Deviation 0.18517
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase CRT Phase: Change at Day 1	-0.0078 units on a scale Standard Deviation 0.13269	0.0176 units on a scale Standard Deviation 0.14066
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase CRT Phase: Change at Day 29	-0.0915 units on a scale Standard Deviation 0.22053	-0.0487 units on a scale Standard Deviation 0.19175
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle1/Day1	-0.0749 units on a scale Standard Deviation 0.22126	-0.0519 units on a scale Standard Deviation 0.17253
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle3/Day1	-0.0203 units on a scale Standard Deviation 0.21340	-0.0160 units on a scale Standard Deviation 0.18179
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle7/Day1	0.0088 units on a scale Standard Deviation 0.16690	0.0140 units on a scale Standard Deviation 0.16240
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle11/Day1	0.0376 units on a scale Standard Deviation 0.21078	0.0792 units on a scale Standard Deviation 0.19287
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle11/Day15	0.0673 units on a scale Standard Deviation 0.17227	0.0389 units on a scale Standard Deviation 0.18732
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at End of treatment	-0.0051 units on a scale Standard Deviation 0.24528	0.0074 units on a scale Standard Deviation 0.24874

SECONDARY outcome

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=333 Participants 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.	Placebo + SOC CRT n=330 Participants 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.
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase CRT Phase: Change at Day 1	-1.1 units on a scale Standard Deviation 13.49	-1.4 units on a scale Standard Deviation 11.39
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase CRT Phase: Change at Day 29	-10.9 units on a scale Standard Deviation 19.94	-9.2 units on a scale Standard Deviation 18.70
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle11/Day15	10.1 units on a scale Standard Deviation 24.69	2.4 units on a scale Standard Deviation 18.20
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Baseline	75.8 units on a scale Standard Deviation 18.20	74.9 units on a scale Standard Deviation 18.24
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle1/Day1	-7.7 units on a scale Standard Deviation 19.05	-6.2 units on a scale Standard Deviation 18.67
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle3/Day1	-1.8 units on a scale Standard Deviation 18.00	-0.7 units on a scale Standard Deviation 16.14
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle7/Day1	-0.6 units on a scale Standard Deviation 14.91	8.6 units on a scale Standard Deviation 81.42
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle7/Day15	4.8 units on a scale Standard Deviation 18.52	3.1 units on a scale Standard Deviation 19.28
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at Cycle11/Day1	0.3 units on a scale Standard Deviation 17.60	4.3 units on a scale Standard Deviation 16.10
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Maintenance Phase: Change at End of treatment	-1.9 units on a scale Standard Deviation 22.55	0.7 units on a scale Standard Deviation 19.28

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=333 Participants 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.	Placebo + SOC CRT n=331 Participants 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.
Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase Baseline	60.56 units on a scale Standard Deviation 13.731	61.05 units on a scale Standard Deviation 13.155
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 CRT Phase: Change at Day 1	-0.59 units on a scale Standard Deviation 8.719	-0.14 units on a scale Standard Deviation 9.136
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 CRT Phase: Change at Day 29	-14.34 units on a scale Standard Deviation 16.847	-14.56 units on a scale Standard Deviation 15.470
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 CRT Phase: Change at Cycle1/Day1	-11.33 units on a scale Standard Deviation 16.054	-12.08 units on a scale Standard Deviation 14.950
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 CRT Phase: Change at Cycle3/Day1	-3.81 units on a scale Standard Deviation 14.017	-2.26 units on a scale Standard Deviation 13.625
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 CRT Phase: Change at Cycle7/Day1	-0.86 units on a scale Standard Deviation 12.503	-0.51 units on a scale Standard Deviation 14.585
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 CRT Phase: Change at Cycle7/Day15	3.96 units on a scale Standard Deviation 14.035	0.92 units on a scale Standard Deviation 14.454
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 CRT Phase: Change at Cycle11/Day1	2.68 units on a scale Standard Deviation 13.367	4.90 units on a scale Standard Deviation 14.207
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 CRT Phase: Change at Cycle11/Day15	3.96 units on a scale Standard Deviation 14.322	3.37 units on a scale Standard Deviation 12.689
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 CRT Phase: Change at End of treatment	-2.35 units on a scale Standard Deviation 17.428	0.79 units on a scale Standard Deviation 16.509

SECONDARY outcome

Timeframe: Baseline (prior to first dose)

Population: 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.

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=299 Participants 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.	Placebo + SOC CRT n=307 Participants 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.
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) Positive Immune Cells	7.4 % of PD-L1+ cells Standard Deviation 7.06	8.3 % of PD-L1+ cells Standard Deviation 8.47
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) Tumor Staining Cells	12.7 % of PD-L1+ cells Standard Deviation 24.90	18.3 % of PD-L1+ cells Standard Deviation 31.12

SECONDARY outcome

Timeframe: Baseline (prior to first dose)

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=289 Participants 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.	Placebo + SOC CRT n=294 Participants 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.
Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells	4.9 % of tumor area occupied by CD8+ cells Standard Deviation 6.03	5.8 % of tumor area occupied by CD8+ cells Standard Deviation 6.55

SECONDARY outcome

Timeframe: From randomization until PD as per investigator assessment (up to 37 months)

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

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=14 Participants 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.	Placebo + SOC CRT n=15 Participants 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.
Percentage of Participants With Positive and Negative Pathology of Neck Dissection Negative Pathology	7.14 percentage of participants	26.70 percentage of participants
Percentage of Participants With Positive and Negative Pathology of Neck Dissection Positive pathology	71.43 percentage of participants	40.00 percentage of participants
Percentage of Participants With Positive and Negative Pathology of Neck Dissection Pathology not reported	21.43 percentage of participants	33.30 percentage of participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=236 Participants 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.	Placebo + SOC CRT 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.
Maximum Plasma Concentration (Cmax) of Avelumab Cycle 2 Day 1	154.9 microgram per milliliter Geometric Coefficient of Variation 97	—
Maximum Plasma Concentration (Cmax) of Avelumab Lead-in/Day 1	203.6 microgram per milliliter Geometric Coefficient of Variation 31	—
Maximum Plasma Concentration (Cmax) of Avelumab CRT/Day 8	190.9 microgram per milliliter Geometric Coefficient of Variation 66	—
Maximum Plasma Concentration (Cmax) of Avelumab CRT/Day 25	162.4 microgram per milliliter Geometric Coefficient of Variation 114	—
Maximum Plasma Concentration (Cmax) of Avelumab Cycle 1 Day 1	142 microgram per milliliter Geometric Coefficient of Variation 117	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=267 Participants 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.	Placebo + SOC CRT 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.
Predose Plasma Concentration (Ctrough) of Avelumab Lead-in/Day 1	2.988 microgram per milliliter Geometric Coefficient of Variation 1590	—
Predose Plasma Concentration (Ctrough) of Avelumab CRT/Day 8	11.9 microgram per milliliter Geometric Coefficient of Variation 63	—
Predose Plasma Concentration (Ctrough) of Avelumab CRT/Day 25	6.284 microgram per milliliter Geometric Coefficient of Variation 138	—
Predose Plasma Concentration (Ctrough) of Avelumab Cycle 1/Day 1	2.354 microgram per milliliter Geometric Coefficient of Variation 131	—
Predose Plasma Concentration (Ctrough) of Avelumab Cycle 2/Day 1	17.56 microgram per milliliter Geometric Coefficient of Variation 70	—
Predose Plasma Concentration (Ctrough) of Avelumab Cycle 5/Day 1	24.35 microgram per milliliter Geometric Coefficient of Variation 66	—
Predose Plasma Concentration (Ctrough) of Avelumab Cycle 8/Day 1	29.59 microgram per milliliter Geometric Coefficient of Variation 69	—
Predose Plasma Concentration (Ctrough) of Avelumab Cycle 11/Day 1	30.85 microgram per milliliter Geometric Coefficient of Variation 79	—

SECONDARY outcome

Timeframe: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=12 Participants 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.	Placebo + SOC CRT n=23 Participants 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.
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin Free Cisplastin	11.84 nanogram per milliliter per milligram Geometric Coefficient of Variation 29	7.286 nanogram per milliliter per milligram Geometric Coefficient of Variation 96
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin Total Cisplastin	26.23 nanogram per milliliter per milligram Geometric Coefficient of Variation 36	25.33 nanogram per milliliter per milligram Geometric Coefficient of Variation 26

SECONDARY outcome

Timeframe: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=10 Participants 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.	Placebo + SOC CRT n=20 Participants 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.
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin Total Cisplatin	299.1 nanogram*hour/milliliter/milligram Geometric Coefficient of Variation 30	332.7 nanogram*hour/milliliter/milligram Geometric Coefficient of Variation 17
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin Free Cisplatin	36.53 nanogram*hour/milliliter/milligram Geometric Coefficient of Variation 51	29.08 nanogram*hour/milliliter/milligram Geometric Coefficient of Variation 49

SECONDARY outcome

Timeframe: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=12 Participants 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.	Placebo + SOC CRT n=23 Participants 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.
Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin Total Cisplatin	3781 nanogram per milliliter Geometric Coefficient of Variation 44	4001 nanogram per milliliter Geometric Coefficient of Variation 34
Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin Free Cisplatin	1710 nanogram per milliliter Geometric Coefficient of Variation 53	1151 nanogram per milliliter Geometric Coefficient of Variation 109

SECONDARY outcome

Timeframe: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase

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

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=12 Participants 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.	Placebo + SOC CRT n=23 Participants 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.
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin Total Cisplatin	1.000 hour Interval 0.5 to 2.4	1.170 hour Interval 0.983 to 24.0
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin Free Cisplatin	1.000 hour Interval 0.5 to 1.17	1.000 hour Interval 0.5 to 2.12

SECONDARY outcome

Timeframe: pre-dose on Day 1 up to 30 Days after the end of treatment

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=331 Participants 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.	Placebo + SOC CRT 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.
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status ADA never-positive	277 Participants	—
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status ADA ever-positive	54 Participants	—

SECONDARY outcome

Timeframe: Day 1 of lead-in phase and on Days 8 and 25 of CRT phase

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

Outcome measures

Outcome data not reported

Adverse Events

Avelumab + Standard of Care Chemotherapy (SOC CRT)

Serious events: 184 serious events

Other events: 344 other events

Deaths: 86 deaths

Placebo + SOC CRT

Serious events: 177 serious events

Other events: 340 other events

Deaths: 62 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Avelumab + Standard of Care Chemotherapy (SOC CRT) n=342 Participants 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.	Placebo + SOC CRT n=336 Participants 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.
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle10/Day 15	-2.5 millimeter of mercury Standard Deviation 10.90	-4.4 millimeter of mercury Standard Deviation 11.69
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle11/Day 1	-2.7 millimeter of mercury Standard Deviation 11.01	-4.6 millimeter of mercury Standard Deviation 11.23
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle11/Day 15	-2.9 millimeter of mercury Standard Deviation 10.37	-3.9 millimeter of mercury Standard Deviation 10.22
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle12/Day 1	-2.1 millimeter of mercury Standard Deviation 9.51	-3.5 millimeter of mercury Standard Deviation 11.40
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure DBP: Baseline	77.8 millimeter of mercury Standard Deviation 10.13	78.1 millimeter of mercury Standard Deviation 10.91
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Lead in Phase: DBP: Change at Day 1	-3.0 millimeter of mercury Standard Deviation 4.24	-8.0 millimeter of mercury Standard Deviation 11.31
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: DBP: Change at Day 1	-1.5 millimeter of mercury Standard Deviation 9.52	-2.2 millimeter of mercury Standard Deviation 9.91
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: DBP: Change at Day 8	-3.8 millimeter of mercury Standard Deviation 10.46	-3.9 millimeter of mercury Standard Deviation 10.99
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: DBP: Change at Day 22	-4.2 millimeter of mercury Standard Deviation 11.77	-5.0 millimeter of mercury Standard Deviation 10.95
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: DBP: Change at Day 25	-3.4 millimeter of mercury Standard Deviation 11.91	-3.3 millimeter of mercury Standard Deviation 11.44
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: DBP: Change at Day 39	-5.7 millimeter of mercury Standard Deviation 11.83	-5.1 millimeter of mercury Standard Deviation 12.14
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: DBP: Change at Day 43	-5.0 millimeter of mercury Standard Deviation 11.49	-4.7 millimeter of mercury Standard Deviation 11.76
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle1/Day 1	-4.8 millimeter of mercury Standard Deviation 11.43	-4.3 millimeter of mercury Standard Deviation 11.67
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle1/Day 15	-3.7 millimeter of mercury Standard Deviation 11.78	-4.0 millimeter of mercury Standard Deviation 10.96
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle2/Day 1	-3.3 millimeter of mercury Standard Deviation 11.74	-3.3 millimeter of mercury Standard Deviation 12.31
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle2/Day 15	-2.7 millimeter of mercury Standard Deviation 11.05	-2.3 millimeter of mercury Standard Deviation 11.82
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle3/Day 1	-2.7 millimeter of mercury Standard Deviation 11.37	-3.6 millimeter of mercury Standard Deviation 11.42
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle3/Day 15	-2.7 millimeter of mercury Standard Deviation 11.09	-3.4 millimeter of mercury Standard Deviation 11.10
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle4/Day 1	-2.2 millimeter of mercury Standard Deviation 12.07	-3.4 millimeter of mercury Standard Deviation 11.42
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle4/Day 15	-2.4 millimeter of mercury Standard Deviation 11.38	-3.3 millimeter of mercury Standard Deviation 11.54
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle5/Day 1	-2.8 millimeter of mercury Standard Deviation 11.61	-3.2 millimeter of mercury Standard Deviation 10.88
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle5/Day 15	-2.5 millimeter of mercury Standard Deviation 11.89	-3.5 millimeter of mercury Standard Deviation 10.69
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle6/Day 1	-3.1 millimeter of mercury Standard Deviation 11.21	-3.8 millimeter of mercury Standard Deviation 11.28
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle6/Day 15	-3.8 millimeter of mercury Standard Deviation 12.20	-4.6 millimeter of mercury Standard Deviation 11.43
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle12/Day 15	-3.3 millimeter of mercury Standard Deviation 11.78	-4.6 millimeter of mercury Standard Deviation 11.19
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle7/Day 1	-4.1 millimeter of mercury Standard Deviation 11.48	-4.2 millimeter of mercury Standard Deviation 11.52
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle7/Day 15	-3.8 millimeter of mercury Standard Deviation 12.05	-3.8 millimeter of mercury Standard Deviation 10.88
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle8/Day 1	-2.9 millimeter of mercury Standard Deviation 11.29	-4.1 millimeter of mercury Standard Deviation 10.95
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle8/Day 15	-3.4 millimeter of mercury Standard Deviation 11.48	-4.0 millimeter of mercury Standard Deviation 12.29
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle9/Day 1	-3.1 millimeter of mercury Standard Deviation 11.78	-4.2 millimeter of mercury Standard Deviation 10.98
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle9/Day 15	-2.1 millimeter of mercury Standard Deviation 11.52	-3.7 millimeter of mercury Standard Deviation 12.07
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle10/Day 1	-2.2 millimeter of mercury Standard Deviation 11.58	-3.5 millimeter of mercury Standard Deviation 11.54
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle13/Day 1	-2.0 millimeter of mercury Standard Deviation 9.60	-3.3 millimeter of mercury Standard Deviation 11.49
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: DBP: Change at Cycle13/Day 15	-1.1 millimeter of mercury Standard Deviation 10.22	-3.8 millimeter of mercury Standard Deviation 11.44
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure DBP: EOT	-2.4 millimeter of mercury Standard Deviation 11.96	-3.2 millimeter of mercury Standard Deviation 11.17
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure SBP: Baseline	129.8 millimeter of mercury Standard Deviation 16.42	130.5 millimeter of mercury Standard Deviation 17.44
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Lead in Phase: SBP: Change at Day 1	-5.5 millimeter of mercury Standard Deviation 2.12	12.5 millimeter of mercury Standard Deviation 6.36
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: SBP: Change at Day 1	-2.5 millimeter of mercury Standard Deviation 15.32	-3.5 millimeter of mercury Standard Deviation 14.82
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: SBP: Change at Day 8	-8.3 millimeter of mercury Standard Deviation 17.78	-8.0 millimeter of mercury Standard Deviation 17.58
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: SBP: Change at Day 22	-8.9 millimeter of mercury Standard Deviation 18.54	-8.4 millimeter of mercury Standard Deviation 17.55
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: SBP: Change at Day 25	-7.9 millimeter of mercury Standard Deviation 19.06	-5.8 millimeter of mercury Standard Deviation 19.51
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: SBP: Change at Day 39	-10.6 millimeter of mercury Standard Deviation 20.51	-10.3 millimeter of mercury Standard Deviation 19.05
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure CRT Phase: SBP: Change at Day 43	-9.6 millimeter of mercury Standard Deviation 18.53	-9.2 millimeter of mercury Standard Deviation 19.52
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle1/Day 1	-9.4 millimeter of mercury Standard Deviation 17.97	-9.4 millimeter of mercury Standard Deviation 20.19
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle1/Day 15	-9.5 millimeter of mercury Standard Deviation 17.73	-8.2 millimeter of mercury Standard Deviation 19.58
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle2/Day 1	-7.0 millimeter of mercury Standard Deviation 18.03	-7.8 millimeter of mercury Standard Deviation 20.09
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at /Cycle2/Day 15	-7.9 millimeter of mercury Standard Deviation 18.55	-6.6 millimeter of mercury Standard Deviation 19.73
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle3/Day 1	-7.3 millimeter of mercury Standard Deviation 18.93	-8.5 millimeter of mercury Standard Deviation 18.04
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle3/Day 15	-8.3 millimeter of mercury Standard Deviation 17.79	-7.1 millimeter of mercury Standard Deviation 19.90
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle4/Day 1	-8.4 millimeter of mercury Standard Deviation 18.01	-8.9 millimeter of mercury Standard Deviation 18.41
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle4/Day 15	-6.2 millimeter of mercury Standard Deviation 18.20	-8.2 millimeter of mercury Standard Deviation 19.62
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Maintenance/Cycle5/Day 1	-7.6 millimeter of mercury Standard Deviation 17.57	-7.7 millimeter of mercury Standard Deviation 18.69
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle5/Day 15	-8.4 millimeter of mercury Standard Deviation 18.69	-7.5 millimeter of mercury Standard Deviation 18.49
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle6/Day 1	-7.6 millimeter of mercury Standard Deviation 17.67	-8.3 millimeter of mercury Standard Deviation 18.96
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle6/Day 15	-7.1 millimeter of mercury Standard Deviation 19.35	-9.4 millimeter of mercury Standard Deviation 19.56
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle7/Day 1	-9.0 millimeter of mercury Standard Deviation 18.30	-8.9 millimeter of mercury Standard Deviation 18.96
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle7/Day 15	-8.7 millimeter of mercury Standard Deviation 18.10	-6.8 millimeter of mercury Standard Deviation 18.73
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle8/Day 1	-6.5 millimeter of mercury Standard Deviation 17.00	-9.4 millimeter of mercury Standard Deviation 18.65
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle8/Day 15	-6.8 millimeter of mercury Standard Deviation 16.69	-7.9 millimeter of mercury Standard Deviation 18.21
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle9/Day 1	-6.1 millimeter of mercury Standard Deviation 18.49	-8.1 millimeter of mercury Standard Deviation 18.41
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle9/Day 15	-6.3 millimeter of mercury Standard Deviation 19.00	-6.7 millimeter of mercury Standard Deviation 20.28
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle10/Day 1	-6.1 millimeter of mercury Standard Deviation 19.24	-7.2 millimeter of mercury Standard Deviation 18.63
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle10/Day 15	-5.6 millimeter of mercury Standard Deviation 17.07	-7.7 millimeter of mercury Standard Deviation 18.76
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle11/Day 1	-6.3 millimeter of mercury Standard Deviation 19.44	-7.7 millimeter of mercury Standard Deviation 18.86
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle11/Day 15	-6.3 millimeter of mercury Standard Deviation 18.99	-7.4 millimeter of mercury Standard Deviation 18.65
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle12/Day 1	-6.8 millimeter of mercury Standard Deviation 18.25	-6.1 millimeter of mercury Standard Deviation 20.21
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle12/Day 15	-7.1 millimeter of mercury Standard Deviation 19.34	-7.8 millimeter of mercury Standard Deviation 19.12
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle13/Day 1	-5.8 millimeter of mercury Standard Deviation 20.04	-6.2 millimeter of mercury Standard Deviation 18.54
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Maintenance Phase: SBP: Change at Cycle13/Day 15	-4.9 millimeter of mercury Standard Deviation 18.82	-5.6 millimeter of mercury Standard Deviation 19.00
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure SBP: EOT	-7.0 millimeter of mercury Standard Deviation 19.83	-4.9 millimeter of mercury Standard Deviation 17.97