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

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ClinicalTrials.gov Identifier: NCT02952586
Recruitment Status : Terminated (The trial prematurely terminated as recommended by the E-DMC because the boundary for futility has been crossed.)
First Posted : November 2, 2016
Results First Posted : February 24, 2021
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Squamous Cell Carcinoma of the Head and Neck
Interventions Drug: Avelumab
Other: Chemoradiation
Enrollment 697
Recruitment Details  
Pre-assignment Details Study had 3 sequential treatment phases: Lead-in, CRT, and Maintenance. There were 3 treatments administered during CRT phase: Avelumab, Cisplatin and IMRT. Reasons for discontinuation are summarized separately for each treatment. If a participant discontinued all 3 treatments due to death, then death is included as reason for discontinuation in each treatment disposition summary. All deaths that are reported as reason for discontinuation at any phase are included in all-cause mortality summary.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment. Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Period Title: Lead-In Phase (7 Days)
Started 350 347
Treated 348 344
Completed 345 343
Not Completed 5 4
Reason Not Completed
Death             0             1
Adverse Event             3             0
No longer met eligibility criteria             0             1
Withdrawal by Subject             2             2
Period Title: CRT for Avelumab or Placebo (63 Days)
Started 345 340 [1]
Completed 312 313
Not Completed 33 27
Reason Not Completed
Death             5             8
Adverse Event             11             12
Physician Decision             3             1
Global deterioration of health status             1             0
Withdrawal by Subject             10             4
Lost to Follow-up             1             1
Other             2             1
[1]
All participants who did not withdraw from study after Lead-In phase, entered into CRT phase
Period Title: CRT for Cisplatin (63 Days)
Started 345 [1] 340 [2]
Completed 234 236
Not Completed 111 104
Reason Not Completed
Death             3             8
Adverse Event             82             81
Physician Decision             12             10
Global deterioration of health status             1             0
Withdrawal by Subject             11             3
Lost to Follow-up             1             1
Other             1             1
[1]
Avelumab, Cisplatin, and IMRT were treatments in CRT phase.
[2]
Placebo, Cisplatin, and IMRT were treatments in CRT phase.
Period Title: CRT for IMRT (63 Days)
Started 345 [1] 340 [2]
Completed 322 320
Not Completed 23 20
Reason Not Completed
Death             5             8
Adverse Event             5             5
Global deterioration of health status             1             0
Withdrawal by Subject             10             6
Lost to Follow-up             1             1
Other             1             0
[1]
Avelumab, Cisplatin, and IMRT were treatments in CRT phase.
[2]
Placebo, Cisplatin, and IMRT were treatments in CRT phase.
Period Title: Maintenance Phase (12 Months)
Started 291 [1] 304 [1]
Completed 107 137
Not Completed 184 167
Reason Not Completed
Death             17             11
Progressive disease             59             53
Adverse Event             24             20
Non-compliance with study drug             1             1
Physician Decision             2             1
Global deterioration of health status             12             5
Withdrawal by Subject             31             25
Lost to Follow-up             1             2
Other             2             1
Ongoing at the time of data cut-off 23-Dec-2019             35             48
[1]
All participants who did not withdraw from study after CRT phases, entered into maintenance phase
Period Title: Follow-Up Phase (90 Days)
Started 231 [1] 236 [1]
Completed 172 179
Not Completed 59 57
Reason Not Completed
Death             12             10
Withdrawal by Subject             6             2
Lost to Follow-up             1             1
Other             5             5
Ongoing at the time of data cut-off 23-Dec-2019             35             39
[1]
Participants who did not withdraw study after previous phases, entered in short-term follow up phase
Period Title: LT Follow-up (up to Approx. 40 Months)
Started 209 [1] 201 [1]
Completed 0 0
Not Completed 209 201
Reason Not Completed
Death             38             27
Withdrawal by Subject             4             1
Lost to Follow-up             1             1
Ongoing at the time of data cut-off 23-Dec-2019             166             172
[1]
Participants who did not withdraw study after previous phases, entered in long-term follow up phase
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT Total
Hide Arm/Group Description Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment. Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment. Total of all reporting groups
Overall Number of Baseline Participants 350 347 697
Hide Baseline Analysis Population Description
The full analysis set (FAS) included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 350 participants 347 participants 697 participants
59.36  (8.56) 58.88  (9.09) 59.12  (8.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 350 participants 347 participants 697 participants
Female
60
  17.1%
62
  17.9%
122
  17.5%
Male
290
  82.9%
285
  82.1%
575
  82.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 350 participants 347 participants 697 participants
Hispanic or Latino
13
   3.7%
8
   2.3%
21
   3.0%
Not Hispanic or Latino
312
  89.1%
312
  89.9%
624
  89.5%
Unknown or Not Reported
25
   7.1%
27
   7.8%
52
   7.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 350 participants 347 participants 697 participants
Black or African American
9
   2.6%
10
   2.9%
19
   2.7%
American Indian or Alaska Native
1
   0.3%
0
   0.0%
1
   0.1%
Asian
102
  29.1%
86
  24.8%
188
  27.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.3%
1
   0.1%
White
224
  64.0%
229
  66.0%
453
  65.0%
Other
14
   4.0%
21
   6.1%
35
   5.0%
1.Primary Outcome
Title Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator
Hide Description PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event.
Time Frame From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 350 347
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(16.9 to NA)
NA [2] 
(23.0 to NA)
[1]
Median and upper limit of 95% CI were not reached at the time of primary completion date. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC Chemotherapy (CRT) arm was crossed and the study was terminated.
[2]
Median and upper limit of 95% CI were not reached at the time of primary completion date. At the time of pre-specified interim analysis for the outcome measure, the futility boundaries for the Avelumab +SOC CRT arm was crossed and the study was terminated.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9199
Comments The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor (T) stage (< T4 vs T4), Nodal (N) stage (N0 /N1/N2a/N2b vs N2c/N3), Human papillomavirus (HPV) status (Positive vs Negative).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.928 to 1.573
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method.
Time Frame From randomization to the date of death or censored date, whichever occurred first (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 350 347
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% CI were not reached at the time of 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.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9372
Comments The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor (T) stage (< T4 vs T4), Nodal (N) stage (N0 /N1/N2a/N2b vs N2c/N3), Human papillomavirus (HPV) status (Positive vs Negative).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
0.927 to 1.849
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site
Hide Description pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site.
Time Frame From randomization until PD or death (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had salvage surgery at the primary site.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0.0 to 45.9)
14.3
(0.4 to 57.9)
4.Secondary Outcome
Title Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator
Hide Description Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method.
Time Frame From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 350 347
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(22.4 to NA)
NA [1] 
(25.0 to NA)
[1]
Median and upper limit of 95% CI were not reached at the time of 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.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9316
Comments The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor (T) stage (< T4 vs T4), Nodal (N) stage (N0 /N1/N2a/N2b vs N2c/N3), Human papillomavirus (HPV) status (Positive vs Negative).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.930 to 1.694
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator
Hide Description Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than [<] 10 millimeter [mm]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (<10 mm short axis) . PR: Greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized.
Time Frame From randomization until disease progression or death, whichever occurred first (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 350 347
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
74.0
(69.1 to 78.5)
74.9
(70.0 to 79.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6229
Comments The treatment arms were compared using a stratified, 1-sided, Cochran-Mantel-Haenszel Test. The 3 stratification factors were tumor stage (< T4 vs T4), Nodal stage (N0 /N1/N2a/N2b vs N2c/N3), HPV status (Positive vs Negative).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.947
Confidence Interval (2-Sided) 95%
0.663 to 1.352
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator
Hide Description Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method.
Time Frame From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 350 347
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(22.8 to NA)
NA [2] 
(NA to NA)
[1]
Median and upper limit of 95% CI were not reached at the time of 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.
[2]
Median and 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.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Standard of Care Chemotherapy (SOC CRT), Placebo + SOC CRT
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9061
Comments The treatment arms were compared using a stratified, 1-sided, log rank Test. The three stratification factors were tumor stage (< T4 vs T4), Nodal stage (N0 /N1/N2a/N2b vs N2c/N3), HPV status (Positive vs Negative).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.909 to 1.624
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator
Hide Description DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:>=30% decrease under baseline of sum of diameters of all target measurable lesions. 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. 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.
Time Frame From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all randomized participants who had unconfirmed CR or PR.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 259 260
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% CI were not reached at the time of 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.
8.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Hide Description Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period.
Time Frame Baseline up to 37 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 348 344
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
10
   2.9%
8
   2.3%
Grade 2
30
   8.6%
53
  15.4%
Grade 3
224
  64.4%
215
  62.5%
Grade 4
59
  17.0%
49
  14.2%
Grade 5
22
   6.3%
17
   4.9%
9.Secondary Outcome
Title Number of Participants With Shift From Baseline in Clinical Laboratory Parameters
Hide Description Grade 1 and 3 ranges are: Anemia:Hb:<LLN-10.0,<8.0 g/dL;LC decreased (dec):<LLN-800/mm^3,500-200/mm^3;LC increased (inc):grade 3:>20,000/mm^3:NC dec:<LLN-1500/mm^3;<1000-500/mm^3;PC dec:<LLN-75,000/mm^3;<50,000-25,000/mm^3;WBC dec:<LLN-3000/mm^3;<2000-1000/mm^3;ALT inc:>ULN-3.0*ULN;>5.0-20.0*ULN;ALP & GGT inc:>ULN-2.5*ULN;>5.0-20.0*ULN;AST inc:>ULN-3.0*ULN;>5.0-20.0*ULN;BB inc:>ULN-1.5*ULN;>3.0-10.0*ULN;CH high:>ULN-300 mg/dL;>400-500 mg/dL;CPK inc:>ULN-2.5*ULN;>5*ULN-10*ULN;Hypercalcemia:>ULN-11.5;>12.5-13.5mg/dL;Hyperglycemia:>ULN-160; >250-500mg/dL;Hyperkalemia:>ULN-5.5;>6.0-7.0mmol/L;Hypermagnesemia:>ULN-3.0;>3.0-8.0 mg/dL;Hypernatremia:>ULN-150; >155-160 mmol/L;Hypertriglyceridemia;150-300;>500-1000 mg/dL;Hypoalbuminemia:<LLN-3;<2g/dL;Hypocalcemia:<LLN-8.0;<8.0-7.0mg/dL;Hypokalemia:<LLN-3.0;<3.0-2.5mmol/L;Hypomagnesemia;<LLN-1.2;<0.9-0.7 mg/dL;Hyponatremia:<LLN-130;<130-120mmol/L; Hypophosphatemia:<LLN-2.5;<2.0-1.0mg/dL;lipase & serum amylase inc:>ULN-1.5*ULN;>2.0-5.0*ULN.
Time Frame Baseline up to end of treatment (EOT) (up to 17 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population include all participants who received at least one dose of study drug. Here "Overall Number of Participants analyzed" signifies number of participants evaluable for this outcome measure and 'Number analyzed' signifies number of participants evaluable for specified rows.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 346 340
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
314
  90.8%
311
  91.5%
Anemia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
42
  12.1%
49
  14.4%
Lymphocyte Count Decreased: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
336
  97.1%
330
  97.1%
Lymphocyte Count (LC) Decreased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
279
  80.6%
284
  83.5%
Lymphocyte Count (LC) Increased: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
7
   2.0%
7
   2.1%
Lymphocyte Count Increased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
0
   0.0%
0
   0.0%
Neutrophil Count (NC) Decreased: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
257
  74.3%
237
  69.7%
Neutrophil Count Decreased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
120
  34.7%
101
  29.7%
Platelet Count (PC) Decreased : New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
157
  45.4%
154
  45.3%
Platelet Count Decreased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
20
   5.8%
7
   2.1%
White Blood Cell (WBC) Decreased: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
309
  89.3%
307
  90.3%
White Blood Cell Decreased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
121
  35.0%
129
  37.9%
Alanine aminotransferase (ALT) increased: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
152
  43.9%
135
  39.7%
ALT increased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
13
   3.8%
2
   0.6%
Alkaline phosphatase increased (ALP): New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
72
  20.8%
49
  14.4%
Alkaline phosphatase increased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
1
   0.3%
1
   0.3%
Aspartate aminotransferase (AST) increased: New or worsened to grade >=1 Number Analyzed 345 participants 340 participants
146
  42.3%
111
  32.6%
Aspartate aminotransferase increased: New or worsened to grade >=3 Number Analyzed 345 participants 340 participants
11
   3.2%
4
   1.2%
Blood bilirubin (BB) increased (BB): New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
58
  16.8%
54
  15.9%
Blood bilirubin increased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
9
   2.6%
4
   1.2%
Cholesterol (CH) high: New or worsened to grade >=1 Number Analyzed 161 participants 164 participants
25
  15.5%
21
  12.8%
Cholesterol high: New or worsened to grade >=3 Number Analyzed 161 participants 164 participants
0
   0.0%
0
   0.0%
CPK increased: New or worsened to grade >=1 Number Analyzed 160 participants 156 participants
7
   4.4%
7
   4.5%
CPK increased: New or worsened to grade >=3 Number Analyzed 160 participants 156 participants
0
   0.0%
1
   0.6%
Creatinine increased: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
334
  96.5%
325
  95.6%
Creatinine increased: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
36
  10.4%
37
  10.9%
GGT increased: New or worsened to grade >=1 Number Analyzed 191 participants 193 participants
37
  19.4%
23
  11.9%
GGT increased: New or worsened to grade >=3 Number Analyzed 191 participants 193 participants
10
   5.2%
5
   2.6%
Hypercalcemia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
67
  19.4%
59
  17.4%
Hypercalcemia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
1
   0.3%
5
   1.5%
Hyperglycemia: New or worsened to grade >=1 Number Analyzed 345 participants 340 participants
144
  41.7%
137
  40.3%
Hyperglycemia: New or worsened to grade >=3 Number Analyzed 345 participants 340 participants
28
   8.1%
29
   8.5%
Hyperkalemia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
106
  30.6%
113
  33.2%
Hyperkalemia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
9
   2.6%
17
   5.0%
Hypermagnesemia: New or worsened to grade >=1 Number Analyzed 346 participants 339 participants
39
  11.3%
40
  11.8%
Hypermagnesemia: New or worsened to grade >=3 Number Analyzed 346 participants 339 participants
10
   2.9%
10
   2.9%
Hypernatremia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
22
   6.4%
20
   5.9%
Hypernatremia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
1
   0.3%
0
   0.0%
Hypertriglyceridemia: New or worsened to grade >=1 Number Analyzed 162 participants 161 participants
35
  21.6%
26
  16.1%
Hypertriglyceridemia: New or worsened to grade >=3 Number Analyzed 162 participants 161 participants
1
   0.6%
2
   1.2%
Hypoalbuminemia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
195
  56.4%
170
  50.0%
Hypoalbuminemia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
7
   2.0%
5
   1.5%
Hypocalcemia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
82
  23.7%
88
  25.9%
Hypocalcemia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
8
   2.3%
14
   4.1%
Hypoglycemia: New or worsened to grade >=1 Number Analyzed 345 participants 340 participants
56
  16.2%
44
  12.9%
Hypoglycemia: New or worsened to grade >=3 Number Analyzed 345 participants 340 participants
2
   0.6%
2
   0.6%
Hypokalemia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
140
  40.5%
122
  35.9%
Hypokalemia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
55
  15.9%
49
  14.4%
Hypomagnesemia: New or worsened to grade >=1 Number Analyzed 346 participants 339 participants
180
  52.0%
158
  46.6%
Hypomagnesemia: New or worsened to grade >=3 Number Analyzed 346 participants 339 participants
8
   2.3%
12
   3.5%
Hyponatremia: New or worsened to grade >=1 Number Analyzed 346 participants 340 participants
232
  67.1%
212
  62.4%
Hyponatremia: New or worsened to grade >=3 Number Analyzed 346 participants 340 participants
74
  21.4%
70
  20.6%
Hypophosphatemia: New or worsened to grade >=1 Number Analyzed 340 participants 339 participants
108
  31.8%
100
  29.5%
Hypophosphatemia: New or worsened to grade >=3 Number Analyzed 340 participants 339 participants
21
   6.2%
19
   5.6%
Lipase increased: New or worsened to grade >=1 Number Analyzed 161 participants 154 participants
19
  11.8%
13
   8.4%
Lipase increased: New or worsened to grade >=3 Number Analyzed 161 participants 154 participants
11
   6.8%
3
   1.9%
Serum amylase increased: New or worsened to grade >=1 Number Analyzed 159 participants 152 participants
13
   8.2%
10
   6.6%
Serum amylase increased: New or worsened to grade >=3 Number Analyzed 159 participants 152 participants
9
   5.7%
5
   3.3%
10.Secondary Outcome
Title Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure
Hide Description Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported.
Time Frame Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 342 336
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury
DBP: Baseline Number Analyzed 342 participants 336 participants
77.8  (10.13) 78.1  (10.91)
Lead in Phase: DBP: Change at Day 1 Number Analyzed 2 participants 2 participants
-3.0  (4.24) -8.0  (11.31)
CRT Phase: DBP: Change at Day 1 Number Analyzed 332 participants 322 participants
-1.5  (9.52) -2.2  (9.91)
CRT Phase: DBP: Change at Day 8 Number Analyzed 323 participants 315 participants
-3.8  (10.46) -3.9  (10.99)
CRT Phase: DBP: Change at Day 22 Number Analyzed 313 participants 309 participants
-4.2  (11.77) -5.0  (10.95)
CRT Phase: DBP: Change at Day 25 Number Analyzed 310 participants 306 participants
-3.4  (11.91) -3.3  (11.44)
CRT Phase: DBP: Change at Day 39 Number Analyzed 309 participants 302 participants
-5.7  (11.83) -5.1  (12.14)
CRT Phase: DBP: Change at Day 43 Number Analyzed 293 participants 283 participants
-5.0  (11.49) -4.7  (11.76)
Maintenance Phase: DBP: Change at Cycle1/Day 1 Number Analyzed 282 participants 290 participants
-4.8  (11.43) -4.3  (11.67)
Maintenance Phase: DBP: Change at Cycle1/Day 15 Number Analyzed 265 participants 279 participants
-3.7  (11.78) -4.0  (10.96)
Maintenance Phase: DBP: Change at Cycle2/Day 1 Number Analyzed 266 participants 277 participants
-3.3  (11.74) -3.3  (12.31)
Maintenance Phase: DBP: Change at Cycle2/Day 15 Number Analyzed 255 participants 272 participants
-2.7  (11.05) -2.3  (11.82)
Maintenance Phase: DBP: Change at Cycle3/Day 1 Number Analyzed 249 participants 262 participants
-2.7  (11.37) -3.6  (11.42)
Maintenance Phase: DBP: Change at Cycle3/Day 15 Number Analyzed 234 participants 255 participants
-2.7  (11.09) -3.4  (11.10)
Maintenance Phase: DBP: Change at Cycle4/Day 1 Number Analyzed 222 participants 247 participants
-2.2  (12.07) -3.4  (11.42)
Maintenance Phase: DBP: Change at Cycle4/Day 15 Number Analyzed 216 participants 240 participants
-2.4  (11.38) -3.3  (11.54)
Maintenance Phase: DBP: Change at Cycle5/Day 1 Number Analyzed 210 participants 241 participants
-2.8  (11.61) -3.2  (10.88)
Maintenance Phase: DBP: Change at Cycle5/Day 15 Number Analyzed 204 participants 232 participants
-2.5  (11.89) -3.5  (10.69)
Maintenance Phase: DBP: Change at Cycle6/Day 1 Number Analyzed 201 participants 226 participants
-3.1  (11.21) -3.8  (11.28)
Maintenance Phase: DBP: Change at Cycle6/Day 15 Number Analyzed 198 participants 230 participants
-3.8  (12.20) -4.6  (11.43)
Maintenance Phase: DBP: Change at Cycle7/Day 1 Number Analyzed 190 participants 220 participants
-4.1  (11.48) -4.2  (11.52)
Maintenance Phase: DBP: Change at Cycle7/Day 15 Number Analyzed 185 participants 214 participants
-3.8  (12.05) -3.8  (10.88)
Maintenance Phase: DBP: Change at Cycle8/Day 1 Number Analyzed 173 participants 209 participants
-2.9  (11.29) -4.1  (10.95)
Maintenance Phase: DBP: Change at Cycle8/Day 15 Number Analyzed 167 participants 194 participants
-3.4  (11.48) -4.0  (12.29)
Maintenance Phase: DBP: Change at Cycle9/Day 1 Number Analyzed 169 participants 198 participants
-3.1  (11.78) -4.2  (10.98)
Maintenance Phase: DBP: Change at Cycle9/Day 15 Number Analyzed 162 participants 194 participants
-2.1  (11.52) -3.7  (12.07)
Maintenance Phase: DBP: Change at Cycle10/Day 1 Number Analyzed 161 participants 192 participants
-2.2  (11.58) -3.5  (11.54)
Maintenance Phase: DBP: Change at Cycle10/Day 15 Number Analyzed 159 participants 191 participants
-2.5  (10.90) -4.4  (11.69)
Maintenance Phase: DBP: Change at Cycle11/Day 1 Number Analyzed 146 participants 179 participants
-2.7  (11.01) -4.6  (11.23)
Maintenance Phase: DBP: Change at Cycle11/Day 15 Number Analyzed 139 participants 162 participants
-2.9  (10.37) -3.9  (10.22)
Maintenance Phase: DBP: Change at Cycle12/Day 1 Number Analyzed 125 participants 156 participants
-2.1  (9.51) -3.5  (11.40)
Maintenance Phase: DBP: Change at Cycle12/Day 15 Number Analyzed 115 participants 146 participants
-3.3  (11.78) -4.6  (11.19)
Maintenance Phase: DBP: Change at Cycle13/Day 1 Number Analyzed 105 participants 132 participants
-2.0  (9.60) -3.3  (11.49)
Maintenance Phase: DBP: Change at Cycle13/Day 15 Number Analyzed 92 participants 118 participants
-1.1  (10.22) -3.8  (11.44)
DBP: EOT Number Analyzed 225 participants 210 participants
-2.4  (11.96) -3.2  (11.17)
SBP: Baseline Number Analyzed 342 participants 336 participants
129.8  (16.42) 130.5  (17.44)
Lead in Phase: SBP: Change at Day 1 Number Analyzed 2 participants 2 participants
-5.5  (2.12) 12.5  (6.36)
CRT Phase: SBP: Change at Day 1 Number Analyzed 332 participants 322 participants
-2.5  (15.32) -3.5  (14.82)
CRT Phase: SBP: Change at Day 8 Number Analyzed 323 participants 315 participants
-8.3  (17.78) -8.0  (17.58)
CRT Phase: SBP: Change at Day 22 Number Analyzed 313 participants 309 participants
-8.9  (18.54) -8.4  (17.55)
CRT Phase: SBP: Change at Day 25 Number Analyzed 310 participants 306 participants
-7.9  (19.06) -5.8  (19.51)
CRT Phase: SBP: Change at Day 39 Number Analyzed 309 participants 302 participants
-10.6  (20.51) -10.3  (19.05)
CRT Phase: SBP: Change at Day 43 Number Analyzed 293 participants 283 participants
-9.6  (18.53) -9.2  (19.52)
Maintenance Phase: SBP: Change at Cycle1/Day 1 Number Analyzed 282 participants 290 participants
-9.4  (17.97) -9.4  (20.19)
Maintenance Phase: SBP: Change at Cycle1/Day 15 Number Analyzed 265 participants 279 participants
-9.5  (17.73) -8.2  (19.58)
Maintenance Phase: SBP: Change at Cycle2/Day 1 Number Analyzed 266 participants 277 participants
-7.0  (18.03) -7.8  (20.09)
Maintenance Phase: SBP: Change at /Cycle2/Day 15 Number Analyzed 255 participants 272 participants
-7.9  (18.55) -6.6  (19.73)
Maintenance Phase: SBP: Change at Cycle3/Day 1 Number Analyzed 249 participants 262 participants
-7.3  (18.93) -8.5  (18.04)
Maintenance Phase: SBP: Change at Cycle3/Day 15 Number Analyzed 234 participants 255 participants
-8.3  (17.79) -7.1  (19.90)
Maintenance Phase: SBP: Change at Cycle4/Day 1 Number Analyzed 222 participants 247 participants
-8.4  (18.01) -8.9  (18.41)
Maintenance Phase: SBP: Change at Cycle4/Day 15 Number Analyzed 216 participants 240 participants
-6.2  (18.20) -8.2  (19.62)
Maintenance Phase: SBP: Change at Maintenance/Cycle5/Day 1 Number Analyzed 210 participants 241 participants
-7.6  (17.57) -7.7  (18.69)
Maintenance Phase: SBP: Change at Cycle5/Day 15 Number Analyzed 204 participants 232 participants
-8.4  (18.69) -7.5  (18.49)
Maintenance Phase: SBP: Change at Cycle6/Day 1 Number Analyzed 201 participants 226 participants
-7.6  (17.67) -8.3  (18.96)
Maintenance Phase: SBP: Change at Cycle6/Day 15 Number Analyzed 198 participants 230 participants
-7.1  (19.35) -9.4  (19.56)
Maintenance Phase: SBP: Change at Cycle7/Day 1 Number Analyzed 190 participants 220 participants
-9.0  (18.30) -8.9  (18.96)
Maintenance Phase: SBP: Change at Cycle7/Day 15 Number Analyzed 185 participants 214 participants
-8.7  (18.10) -6.8  (18.73)
Maintenance Phase: SBP: Change at Cycle8/Day 1 Number Analyzed 173 participants 209 participants
-6.5  (17.00) -9.4  (18.65)
Maintenance Phase: SBP: Change at Cycle8/Day 15 Number Analyzed 167 participants 194 participants
-6.8  (16.69) -7.9  (18.21)
Maintenance Phase: SBP: Change at Cycle9/Day 1 Number Analyzed 169 participants 198 participants
-6.1  (18.49) -8.1  (18.41)
Maintenance Phase: SBP: Change at Cycle9/Day 15 Number Analyzed 162 participants 194 participants
-6.3  (19.00) -6.7  (20.28)
Maintenance Phase: SBP: Change at Cycle10/Day 1 Number Analyzed 161 participants 192 participants
-6.1  (19.24) -7.2  (18.63)
Maintenance Phase: SBP: Change at Cycle10/Day 15 Number Analyzed 159 participants 191 participants
-5.6  (17.07) -7.7  (18.76)
Maintenance Phase: SBP: Change at Cycle11/Day 1 Number Analyzed 146 participants 179 participants
-6.3  (19.44) -7.7  (18.86)
Maintenance Phase: SBP: Change at Cycle11/Day 15 Number Analyzed 139 participants 162 participants
-6.3  (18.99) -7.4  (18.65)
Maintenance Phase: SBP: Change at Cycle12/Day 1 Number Analyzed 125 participants 156 participants
-6.8  (18.25) -6.1  (20.21)
Maintenance Phase: SBP: Change at Cycle12/Day 15 Number Analyzed 115 participants 146 participants
-7.1  (19.34) -7.8  (19.12)
Maintenance Phase: SBP: Change at Cycle13/Day 1 Number Analyzed 105 participants 132 participants
-5.8  (20.04) -6.2  (18.54)
Maintenance Phase: SBP: Change at Cycle13/Day 15 Number Analyzed 92 participants 118 participants
-4.9  (18.82) -5.6  (19.00)
SBP: EOT Number Analyzed 225 participants 210 participants
-7.0  (19.83) -4.9  (17.97)
11.Secondary Outcome
Title Change From Baseline in Vital Sign - Pulse Rate
Hide Description Change from baseline in pulse rate in sitting position in beats per minute was reported.
Time Frame Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 342 336
Mean (Standard Deviation)
Unit of Measure: beats per minute
Baseline Number Analyzed 342 participants 336 participants
79.9  (13.72) 86.0  (43.0)
Lead in Phase: Change at Day 1 Number Analyzed 2 participants 2 participants
-3.5  (0.71) -8.5  (19.09)
CRT Phase: Change at Day 1 Number Analyzed 331 participants 322 participants
0.7  (11.70) 1.3  (10.92)
CRT Phase: Change at Day 8 Number Analyzed 323 participants 315 participants
1.5  (13.15) 2.2  (12.42)
CRT Phase: Change at Day 22 Number Analyzed 314 participants 309 participants
0.5  (13.86) 2.6  (12.24)
CRT Phase: Change at Day 25 Number Analyzed 310 participants 306 participants
-1.6  (14.87) -1.2  (13.90)
CRT Phase: Change at Day 29 Number Analyzed 10 participants 8 participants
-11.0  (20.47) 3.6  (21.29)
CRT Phase: Change at Day 39 Number Analyzed 310 participants 301 participants
4.0  (15.46) 4.3  (14.71)
CRT Phase: Change at Day 43 Number Analyzed 293 participants 283 participants
4.7  (16.82) 6.1  (14.78)
Maintenance Phase: Change at Cycle1/Day 1 Number Analyzed 282 participants 291 participants
5.1  (16.23) 7.5  (14.43)
Maintenance Phase: Change at Cycle1/Day 15 Number Analyzed 265 participants 279 participants
3.8  (15.04) 6.3  (13.65)
Maintenance Phase: Change at Cycle2/Day 1 Number Analyzed 266 participants 277 participants
3.5  (15.30) 5.9  (14.74)
Maintenance Phase: Change at Cycle2/Day 15 Number Analyzed 254 participants 272 participants
4.1  (15.32) 4.9  (13.94)
Maintenance Phase: Change at Cycle3/Day 1 Number Analyzed 249 participants 262 participants
3.5  (14.49) 3.9  (14.37)
Maintenance Phase: Change at Cycle3/Day 15 Number Analyzed 234 participants 255 participants
2.8  (14.73) 2.8  (14.14)
Maintenance Phase: Change at Cycle4/Day 1 Number Analyzed 222 participants 247 participants
1.8  (14.79) 3.8  (14.95)
Maintenance Phase: Change at Cycle4/Day 15 Number Analyzed 216 participants 240 participants
1.6  (14.80) 3.8  (15.02)
Maintenance Phase: Change at Cycle5/Day 1 Number Analyzed 210 participants 241 participants
2.6  (13.88) 2.9  (14.82)
Maintenance Phase: Change at Cycle5/Day 15 Number Analyzed 204 participants 232 participants
1.6  (15.11) 3.3  (13.74)
Maintenance Phase: Change at Cycle6/Day 1 Number Analyzed 201 participants 226 participants
1.6  (15.42) 2.7  (15.72)
Maintenance Phase: Change at Cycle6/Day 15 Number Analyzed 198 participants 230 participants
0.4  (14.04) 1.4  (13.66)
Maintenance Phase: Change at Cycle7/Day 1 Number Analyzed 190 participants 220 participants
-0.1  (14.47) 2.5  (14.18)
Maintenance Phase: Change at Cycle7/Day 15 Number Analyzed 185 participants 214 participants
-0.1  (14.24) 1.4  (14.33)
Maintenance Phase: Change at Cycle8/Day 1 Number Analyzed 173 participants 209 participants
-0.2  (13.84) 1.0  (13.67)
Maintenance Phase: Change at Cycle8/Day 15 Number Analyzed 167 participants 194 participants
-1.5  (14.52) 1.5  (14.86)
Maintenance Phase: Change at Cycle9/Day 1 Number Analyzed 169 participants 198 participants
-1.0  (14.29) -0.1  (14.06)
Maintenance Phase: Change at Cycle9/Day 15 Number Analyzed 162 participants 194 participants
-1.0  (14.20) 0.2  (14.44)
Maintenance Phase: Change at Cycle10/Day 1 Number Analyzed 161 participants 192 participants
-0.9  (13.40) 0.7  (14.52)
Maintenance Phase: Change at Cycle10/Day 15 Number Analyzed 159 participants 191 participants
-0.5  (15.33) 0.7  (14.66)
Maintenance Phase: Change at Cycle11/Day 1 Number Analyzed 145 participants 178 participants
-1.6  (14.57) 0.2  (14.01)
Maintenance Phase: Change at Cycle11/Day 15 Number Analyzed 139 participants 162 participants
-0.2  (13.23) 0.3  (12.93)
Maintenance Phase: Change at Cycle12/Day 1 Number Analyzed 125 participants 156 participants
-0.3  (13.92) 0.4  (13.67)
Maintenance Phase: Change at Cycle12/Day 15 Number Analyzed 115 participants 146 participants
-1.4  (14.92) -0.5  (12.47)
Maintenance Phase: Change at Cycle13/Day 1 Number Analyzed 105 participants 132 participants
-1.4  (14.09) -0.1  (12.22)
Maintenance Phase: Change at Cycle13/Day 15 Number Analyzed 92 participants 118 participants
-1.3  (15.57) 0.4  (13.24)
EOT Number Analyzed 223 participants 210 participants
0.2  (14.73) 1.9  (14.09)
12.Secondary Outcome
Title Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase
Hide Description EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Time Frame Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 334 333
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 334 participants 333 participants
0.7718  (0.17822) 0.7615  (0.18517)
CRT Phase: Change at Day 1 Number Analyzed 321 participants 318 participants
-0.0078  (0.13269) 0.0176  (0.14066)
CRT Phase: Change at Day 29 Number Analyzed 293 participants 276 participants
-0.0915  (0.22053) -0.0487  (0.19175)
Maintenance Phase: Change at Cycle1/Day1 Number Analyzed 272 participants 279 participants
-0.0749  (0.22126) -0.0519  (0.17253)
Maintenance Phase: Change at Cycle3/Day1 Number Analyzed 239 participants 243 participants
-0.0203  (0.21340) -0.0160  (0.18179)
Maintenance Phase: Change at Cycle7/Day1 Number Analyzed 95 participants 113 participants
0.0088  (0.16690) 0.0140  (0.16240)
Maintenance Phase: Change at Cycle7/Day15 Number Analyzed 59 participants 79 participants
0.0552  (0.18544) 0.0472  (0.17990)
Maintenance Phase: Change at Cycle11/Day1 Number Analyzed 90 participants 111 participants
0.0376  (0.21078) 0.0792  (0.19287)
Maintenance Phase: Change at Cycle11/Day15 Number Analyzed 36 participants 40 participants
0.0673  (0.17227) 0.0389  (0.18732)
Maintenance Phase: Change at End of treatment Number Analyzed 184 participants 187 participants
-0.0051  (0.24528) 0.0074  (0.24874)
13.Secondary Outcome
Title Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase
Hide Description EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status.
Time Frame Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 333 330
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 333 participants 330 participants
75.8  (18.20) 74.9  (18.24)
CRT Phase: Change at Day 1 Number Analyzed 317 participants 314 participants
-1.1  (13.49) -1.4  (11.39)
CRT Phase: Change at Day 29 Number Analyzed 291 participants 271 participants
-10.9  (19.94) -9.2  (18.70)
Maintenance Phase: Change at Cycle1/Day1 Number Analyzed 272 participants 277 participants
-7.7  (19.05) -6.2  (18.67)
Maintenance Phase: Change at Cycle3/Day1 Number Analyzed 240 participants 236 participants
-1.8  (18.00) -0.7  (16.14)
Maintenance Phase: Change at Cycle7/Day1 Number Analyzed 95 participants 113 participants
-0.6  (14.91) 8.6  (81.42)
Maintenance Phase: Change at Cycle7/Day15 Number Analyzed 59 participants 78 participants
4.8  (18.52) 3.1  (19.28)
Maintenance Phase: Change at Cycle11/Day1 Number Analyzed 89 participants 108 participants
0.3  (17.60) 4.3  (16.10)
Maintenance Phase: Change at Cycle11/Day15 Number Analyzed 37 participants 40 participants
10.1  (24.69) 2.4  (18.20)
Maintenance Phase: Change at End of treatment Number Analyzed 183 participants 184 participants
-1.9  (22.55) 0.7  (19.28)
14.Secondary Outcome
Title Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase
Hide Description The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning.
Time Frame Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified time point.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 333 331
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 333 participants 331 participants
60.56  (13.731) 61.05  (13.155)
CRT Phase: Change at Day 1 Number Analyzed 318 participants 317 participants
-0.59  (8.719) -0.14  (9.136)
CRT Phase: Change at Day 29 Number Analyzed 294 participants 275 participants
-14.34  (16.847) -14.56  (15.470)
CRT Phase: Change at Cycle1/Day1 Number Analyzed 272 participants 281 participants
-11.33  (16.054) -12.08  (14.950)
CRT Phase: Change at Cycle3/Day1 Number Analyzed 241 participants 241 participants
-3.81  (14.017) -2.26  (13.625)
CRT Phase: Change at Cycle7/Day1 Number Analyzed 96 participants 113 participants
-0.86  (12.503) -0.51  (14.585)
CRT Phase: Change at Cycle7/Day15 Number Analyzed 61 participants 78 participants
3.96  (14.035) 0.92  (14.454)
CRT Phase: Change at Cycle11/Day1 Number Analyzed 88 participants 110 participants
2.68  (13.367) 4.90  (14.207)
CRT Phase: Change at Cycle11/Day15 Number Analyzed 37 participants 40 participants
3.96  (14.322) 3.37  (12.689)
CRT Phase: Change at End of treatment Number Analyzed 184 participants 187 participants
-2.35  (17.428) 0.79  (16.509)
15.Secondary Outcome
Title Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
Hide Description PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells.
Time Frame Baseline (prior to first dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Biomarker analysis set was a subset of the safety analysis set included participants who had at least one screening biomarker assessment. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 299 307
Mean (Standard Deviation)
Unit of Measure: % of PD-L1+ cells
Positive Immune Cells 7.4  (7.06) 8.3  (8.47)
Tumor Staining Cells 12.7  (24.90) 18.3  (31.12)
16.Secondary Outcome
Title Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells
Hide Description Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm^2).
Time Frame Baseline (prior to first dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Biomarker analysis set included all participants who had received at least one dose of study drug and who had at least one screening biomarker assessment. Here, 'Overall number of participants Analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 289 294
Mean (Standard Deviation)
Unit of Measure: % of tumor area occupied by CD8+ cells
4.9  (6.03) 5.8  (6.55)
17.Secondary Outcome
Title Percentage of Participants With Positive and Negative Pathology of Neck Dissection
Hide Description Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study.
Time Frame From randomization until PD as per investigator assessment (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least one dose of study drug and who had salvage neck dissection.
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description:
Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
Overall Number of Participants Analyzed 14 15
Measure Type: Number
Unit of Measure: percentage of participants
Negative Pathology 7.14 26.70
Positive pathology 71.43 40.00
Pathology not reported 21.43 33.30
18.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Avelumab
Hide Description [Not Specified]
Time Frame Pre-dose, end of infusion on Day 1 of lead-in phase and on Days 8, 25 of CRT phase
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Predose Plasma Concentration (Ctrough) of Avelumab
Hide Description [Not Specified]
Time Frame Pre-dose, end of infusion on Day 1 of lead-in phase and on Days 8, 25 of CRT phase
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Avelumab
Hide Description [Not Specified]
Time Frame Pre-dose, end of infusion on Day 1 of lead-in phase and on Days 8, 25 of CRT phase
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Cisplatin
Hide Description [Not Specified]
Time Frame Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Cisplatin
Hide Description [Not Specified]
Time Frame Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Outcome Measure Data Not Reported
23.Secondary Outcome
Title Clearance (CL) of Cisplatin
Hide Description [Not Specified]
Time Frame Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Outcome Measure Data Not Reported
24.Secondary Outcome
Title Time to Attain Maximum Observed Plasma Concentration (Tmax) of Cisplatin
Hide Description [Not Specified]
Time Frame Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Outcome Measure Data Not Reported
25.Secondary Outcome
Title Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
Hide Description [Not Specified]
Time Frame Day 1 of lead-in phase and on Days 8 and 25 of CRT phase
Outcome Measure Data Not Reported
26.Secondary Outcome
Title Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status
Hide Description [Not Specified]
Time Frame Day 1 of lead-in phase and on Days 8 and 25 of CRT phase
Outcome Measure Data Not Reported
Time Frame Baseline up to 37 months
Adverse Event Reporting Description Same event may appear as AE, serious AE, here distinct events are presented.Event may be serious in 1 participant and non-serious in another or 1 participant may have experienced both serious, non-serious event.Safety analysis set evaluated.If a participant discontinued all 3 treatments of CRT phase due to death then death is included as discontinuation reason in each treatment disposition summary. All deaths reported as reason of discontinuation at any phase are included in all-cause mortality.
 
Arm/Group Title Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Hide Arm/Group Description Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment. Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment, If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment.
All-Cause Mortality
Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Affected / at Risk (%) Affected / at Risk (%)
Total   73/348 (20.98%)   58/344 (16.86%) 
Hide Serious Adverse Events
Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Affected / at Risk (%) Affected / at Risk (%)
Total   184/348 (52.87%)   175/344 (50.87%) 
Blood and lymphatic system disorders     
Anaemia * 1  8/348 (2.30%)  12/344 (3.49%) 
Bone marrow failure * 1  2/348 (0.57%)  1/344 (0.29%) 
Febrile neutropenia * 1  9/348 (2.59%)  5/344 (1.45%) 
Leukopenia * 1  1/348 (0.29%)  0/344 (0.00%) 
Lymphadenopathy * 1  0/348 (0.00%)  1/344 (0.29%) 
Neutropenia * 1  4/348 (1.15%)  3/344 (0.87%) 
Splenic haematoma * 1  1/348 (0.29%)  0/344 (0.00%) 
Thrombocytopenia * 1  1/348 (0.29%)  0/344 (0.00%) 
Cardiac disorders     
Acute coronary syndrome * 1  1/348 (0.29%)  0/344 (0.00%) 
Acute myocardial infarction * 1  1/348 (0.29%)  1/344 (0.29%) 
Angina pectoris * 1  0/348 (0.00%)  1/344 (0.29%) 
Atrial fibrillation * 1  0/348 (0.00%)  1/344 (0.29%) 
Bradycardia * 1  1/348 (0.29%)  2/344 (0.58%) 
Cardiac arrest * 1  1/348 (0.29%)  0/344 (0.00%) 
Cardiac failure * 1  1/348 (0.29%)  2/344 (0.58%) 
Cardiac failure congestive * 1  1/348 (0.29%)  0/344 (0.00%) 
Cardio-respiratory arrest * 1  1/348 (0.29%)  0/344 (0.00%) 
Sinus tachycardia * 1  0/348 (0.00%)  1/344 (0.29%) 
Supraventricular tachycardia * 1  2/348 (0.57%)  0/344 (0.00%) 
Tachycardia * 1  0/348 (0.00%)  1/344 (0.29%) 
Ear and labyrinth disorders     
Deafness * 1  1/348 (0.29%)  0/344 (0.00%) 
Tinnitus * 1  0/348 (0.00%)  1/344 (0.29%) 
Vertigo * 1  1/348 (0.29%)  0/344 (0.00%) 
Endocrine disorders     
Adrenal insufficiency * 1  0/348 (0.00%)  1/344 (0.29%) 
Hyperthyroidism * 1  0/348 (0.00%)  1/344 (0.29%) 
Eye disorders     
Pterygium * 1  0/348 (0.00%)  1/344 (0.29%) 
Retinal detachment * 1  0/348 (0.00%)  1/344 (0.29%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/348 (0.00%)  2/344 (0.58%) 
Colitis * 1  1/348 (0.29%)  2/344 (0.58%) 
Constipation * 1  1/348 (0.29%)  1/344 (0.29%) 
Diarrhoea * 1  1/348 (0.29%)  2/344 (0.58%) 
Dry mouth * 1  0/348 (0.00%)  1/344 (0.29%) 
Duodenal ulcer perforation * 1  1/348 (0.29%)  0/344 (0.00%) 
Dyspepsia * 1  1/348 (0.29%)  0/344 (0.00%) 
Dysphagia * 1  15/348 (4.31%)  13/344 (3.78%) 
Faecaloma * 1  0/348 (0.00%)  1/344 (0.29%) 
Gastric perforation * 1  1/348 (0.29%)  1/344 (0.29%) 
Haematemesis * 1  1/348 (0.29%)  1/344 (0.29%) 
Haematochezia * 1  1/348 (0.29%)  0/344 (0.00%) 
Large intestinal obstruction * 1  0/348 (0.00%)  1/344 (0.29%) 
Mouth haemorrhage * 1  2/348 (0.57%)  2/344 (0.58%) 
Mouth swelling * 1  0/348 (0.00%)  1/344 (0.29%) 
Nausea * 1  7/348 (2.01%)  9/344 (2.62%) 
Odynophagia * 1  3/348 (0.86%)  1/344 (0.29%) 
Oesophageal obstruction * 1  1/348 (0.29%)  0/344 (0.00%) 
Oesophagitis * 1  1/348 (0.29%)  1/344 (0.29%) 
Oral pain * 1  1/1 (100.00%)  2/344 (0.58%) 
Pneumoperitoneum * 1  1/348 (0.29%)  0/344 (0.00%) 
Salivary hypersecretion * 1  1/348 (0.29%)  0/344 (0.00%) 
Stomatitis * 1  7/348 (2.01%)  4/344 (1.16%) 
Tongue haemorrhage * 1  2/348 (0.57%)  0/344 (0.00%) 
Tongue ulceration * 1  1/348 (0.29%)  0/344 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/348 (0.29%)  0/344 (0.00%) 
Vomiting * 1  11/348 (3.16%)  12/344 (3.49%) 
General disorders     
Asthenia * 1  2/348 (0.57%)  6/344 (1.74%) 
Chest pain * 1  2/348 (0.57%)  1/344 (0.29%) 
Chills * 1  2/348 (0.57%)  0/344 (0.00%) 
Condition aggravated * 1  1/348 (0.29%)  0/344 (0.00%) 
Death * 1  2/348 (0.57%)  1/344 (0.29%) 
Disease progression * 1  1/348 (0.29%)  1/344 (0.29%) 
Fatigue * 1  2/348 (0.57%)  2/344 (0.58%) 
General physical health deterioration * 1  1/348 (0.29%)  6/344 (1.74%) 
Hyperpyrexia * 1  1/348 (0.29%)  0/344 (0.00%) 
Hyperthermia * 1  0/348 (0.00%)  2/344 (0.58%) 
Hypothermia * 1  0/348 (0.00%)  1/344 (0.29%) 
Ill-defined disorder * 1  0/348 (0.00%)  1/344 (0.29%) 
Malaise * 1  0/348 (0.00%)  1/344 (0.29%) 
Mucosal inflammation * 1  5/348 (1.44%)  6/344 (1.74%) 
Pain * 1  0/348 (0.00%)  2/344 (0.58%) 
Performance status decreased * 1  0/348 (0.00%)  1/344 (0.29%) 
Pyrexia * 1  11/348 (3.16%)  3/344 (0.87%) 
Sudden death * 1  0/348 (0.00%)  1/344 (0.29%) 
Swelling * 1  1/348 (0.29%)  0/344 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis * 1  0/348 (0.00%)  1/344 (0.29%) 
Hepatitis * 1  1/348 (0.29%)  0/344 (0.00%) 
Hepatotoxicity * 1  1/348 (0.29%)  0/344 (0.00%) 
Infections and infestations     
Abdominal abscess * 1  1/348 (0.29%)  0/344 (0.00%) 
Abscess oral * 1  0/348 (0.00%)  1/344 (0.29%) 
Anal abscess * 1  0/348 (0.00%)  1/344 (0.29%) 
Appendicitis * 1  0/348 (0.00%)  1/344 (0.29%) 
Bacterial infection * 1  0/348 (0.00%)  1/344 (0.29%) 
Bronchitis * 1  1/348 (0.29%)  1/344 (0.29%) 
Bronchitis bacterial * 1  1/348 (0.29%)  0/344 (0.00%) 
Candida infection * 1  1/348 (0.29%)  0/344 (0.00%) 
Cellulitis * 1  3/348 (0.86%)  2/344 (0.58%) 
Device related infection * 1  2/348 (0.57%)  1/344 (0.29%) 
Device related sepsis * 1  1/348 (0.29%)  0/344 (0.00%) 
Endocarditis * 1  0/348 (0.00%)  1/344 (0.29%) 
Endocarditis candida * 1  1/348 (0.29%)  0/344 (0.00%) 
Enterocolitis infectious * 1  2/348 (0.57%)  0/344 (0.00%) 
Epididymitis * 1  1/348 (0.29%)  0/344 (0.00%) 
Epiglottitis * 1  1/348 (0.29%)  0/344 (0.00%) 
Herpes zoster * 1  1/348 (0.29%)  0/344 (0.00%) 
Infection * 1  1/348 (0.29%)  3/344 (0.87%) 
Infectious pleural effusion * 1  0/348 (0.00%)  1/344 (0.29%) 
Localised infection * 1  1/348 (0.29%)  0/344 (0.00%) 
Lower respiratory tract infection * 1  2/348 (0.57%)  2/344 (0.58%) 
Lower respiratory tract infection bacterial * 1  0/348 (0.00%)  1/344 (0.29%) 
Lung abscess * 1  1/348 (0.29%)  0/344 (0.00%) 
Neutropenic infection * 1  1/348 (0.29%)  0/344 (0.00%) 
Neutropenic sepsis * 1  1/348 (0.29%)  0/344 (0.00%) 
Oesophageal candidiasis * 1  1/348 (0.29%)  0/344 (0.00%) 
Oral candidiasis * 1  0/348 (0.00%)  1/344 (0.29%) 
Oral infection * 1  0/348 (0.00%)  1/344 (0.29%) 
Parotitis * 1  2/348 (0.57%)  1/344 (0.29%) 
Pharyngitis * 1  0/348 (0.00%)  2/344 (0.58%) 
Pneumococcal sepsis * 1  1/348 (0.29%)  0/344 (0.00%) 
Pneumonia * 1  25/348 (7.18%)  20/344 (5.81%) 
Pneumonia bacterial * 1  2/348 (0.57%)  0/344 (0.00%) 
Respiratory tract infection * 1  4/348 (1.15%)  0/344 (0.00%) 
Sepsis * 1  7/348 (2.01%)  5/344 (1.45%) 
Sinusitis * 1  1/348 (0.29%)  0/344 (0.00%) 
Skin infection * 1  1/348 (0.29%)  0/344 (0.00%) 
Soft tissue infection * 1  1/348 (0.29%)  1/344 (0.29%) 
Staphylococcal sepsis * 1  1/348 (0.29%)  0/344 (0.00%) 
Stoma site abscess * 1  1/348 (0.29%)  0/344 (0.00%) 
Stoma site infection * 1  1/348 (0.29%)  1/344 (0.29%) 
Urinary tract infection * 1  2/348 (0.57%)  1/344 (0.29%) 
Vascular device infection * 1  1/348 (0.29%)  0/344 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture * 1  1/348 (0.29%)  0/344 (0.00%) 
Femur fracture * 1  1/348 (0.29%)  0/344 (0.00%) 
Gastrostomy failure * 1  1/348 (0.29%)  0/344 (0.00%) 
Infusion related reaction * 1  2/348 (0.57%)  0/344 (0.00%) 
Nerve injury * 1  0/348 (0.00%)  1/344 (0.29%) 
Overdose * 1  1/348 (0.29%)  0/344 (0.00%) 
Pancreatic injury * 1  0/348 (0.00%)  1/344 (0.29%) 
Post procedural fever * 1  1/348 (0.29%)  0/344 (0.00%) 
Post procedural haemorrhage * 1  2/348 (0.57%)  1/344 (0.29%) 
Radiation associated pain * 1  0/348 (0.00%)  1/344 (0.29%) 
Radiation fibrosis * 1  1/348 (0.29%)  0/344 (0.00%) 
Radiation injury * 1  0/348 (0.00%)  1/344 (0.29%) 
Radiation mucositis * 1  0/348 (0.00%)  2/344 (0.58%) 
Radiation necrosis * 1  0/348 (0.00%)  1/344 (0.29%) 
Radiation skin injury * 1  3/348 (0.86%)  2/344 (0.58%) 
Stoma site inflammation * 1  0/348 (0.00%)  1/344 (0.29%) 
Stoma site pain * 1  0/348 (0.00%)  1/344 (0.29%) 
Subdural haemorrhage * 1  1/348 (0.29%)  0/344 (0.00%) 
Thermal burn * 1  0/348 (0.00%)  1/344 (0.29%) 
Tracheal haemorrhage * 1  2/348 (0.57%)  0/344 (0.00%) 
Tracheal obstruction * 1  1/348 (0.29%)  0/344 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/348 (0.29%)  0/344 (0.00%) 
Blood creatinine increased * 1  7/348 (2.01%)  5/344 (1.45%) 
C-reactive protein increased * 1  0/348 (0.00%)  1/344 (0.29%) 
Eastern Cooperative Oncology Group performance status worsened * 1  0/348 (0.00%)  1/344 (0.29%) 
Hepatic enzyme increased * 1  1/348 (0.29%)  0/344 (0.00%) 
Liver function test abnormal * 1  0/348 (0.00%)  1/344 (0.29%) 
Liver function test increased * 1  1/348 (0.29%)  0/344 (0.00%) 
Lymphocyte count decreased * 1  0/348 (0.00%)  1/344 (0.29%) 
Neutrophil count decreased * 1  4/348 (1.15%)  1/344 (0.29%) 
Oxygen saturation decreased * 1  1/348 (0.29%)  0/344 (0.00%) 
Weight decreased * 1  5/348 (1.44%)  3/344 (0.87%) 
White blood cell count decreased * 1  0/348 (0.00%)  1/344 (0.29%) 
Metabolism and nutrition disorders     
Adult failure to thrive * 1  0/348 (0.00%)  1/344 (0.29%) 
Cachexia * 1  2/348 (0.57%)  2/344 (0.58%) 
Decreased appetite * 1  5/348 (1.44%)  3/344 (0.87%) 
Dehydration * 1  9/348 (2.59%)  15/344 (4.36%) 
Diabetes mellitus inadequate control * 1  1/348 (0.29%)  0/344 (0.00%) 
Diabetic ketoacidosis * 1  0/348 (0.00%)  1/344 (0.29%) 
Electrolyte imbalance * 1  1/348 (0.29%)  0/344 (0.00%) 
Failure to thrive * 1  2/348 (0.57%)  1/344 (0.29%) 
Fluid overload * 1  1/348 (0.29%)  0/344 (0.00%) 
Hypercalcaemia * 1  1/348 (0.29%)  1/344 (0.29%) 
Hyperglycaemia * 1  2/348 (0.57%)  0/344 (0.00%) 
Hyperglycaemic hyperosmolar nonketotic syndrome * 1  1/348 (0.29%)  0/344 (0.00%) 
Hypoalbuminaemia * 1  0/348 (0.00%)  1/344 (0.29%) 
Hypocalcaemia * 1  0/348 (0.00%)  2/344 (0.58%) 
Hypoglycaemia * 1  0/348 (0.00%)  1/344 (0.29%) 
Hypokalaemia * 1  4/348 (1.15%)  3/344 (0.87%) 
Hyponatraemia * 1  4/348 (1.15%)  7/344 (2.03%) 
Hypophagia * 1  1/348 (0.29%)  0/344 (0.00%) 
Ketoacidosis * 1  0/348 (0.00%)  1/344 (0.29%) 
Malnutrition * 1  2/348 (0.57%)  3/344 (0.87%) 
Metabolic disorder * 1  0/348 (0.00%)  1/344 (0.29%) 
Musculoskeletal and connective tissue disorders     
Arthritis * 1  1/348 (0.29%)  0/344 (0.00%) 
Back pain * 1  0/348 (0.00%)  1/344 (0.29%) 
Haematoma muscle * 1  0/348 (0.00%)  1/344 (0.29%) 
Neck pain * 1  1/348 (0.29%)  1/344 (0.29%) 
Oligoarthritis * 1  1/348 (0.29%)  0/344 (0.00%) 
Osteonecrosis of jaw * 1  0/348 (0.00%)  1/344 (0.29%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant melanoma * 1  0/348 (0.00%)  1/344 (0.29%) 
Non-small cell lung cancer * 1  1/348 (0.29%)  0/344 (0.00%) 
Oesophageal carcinoma * 1  0/348 (0.00%)  1/344 (0.29%) 
Oesophageal neoplasm * 1  1/348 (0.29%)  0/344 (0.00%) 
Plasmacytoma * 1  0/348 (0.00%)  1/344 (0.29%) 
Transitional cell cancer of the renal pelvis and ureter * 1  1/348 (0.29%)  0/344 (0.00%) 
Tumour haemorrhage * 1  4/348 (1.15%)  4/344 (1.16%) 
Nervous system disorders     
Brain hypoxia * 1  1/348 (0.29%)  0/344 (0.00%) 
Cerebral ischaemia * 1  0/348 (0.00%)  1/344 (0.29%) 
Cerebrovascular accident * 1  1/348 (0.29%)  1/344 (0.29%) 
Coma * 1  1/348 (0.29%)  0/344 (0.00%) 
Depressed level of consciousness * 1  0/348 (0.00%)  1/344 (0.29%) 
Dizziness * 1  0/348 (0.00%)  1/344 (0.29%) 
Epilepsy * 1  1/348 (0.29%)  1/344 (0.29%) 
Headache * 1  1/348 (0.29%)  0/344 (0.00%) 
Presyncope * 1  0/348 (0.00%)  1/344 (0.29%) 
Seizure * 1  0/348 (0.00%)  1/344 (0.29%) 
Subacute combined cord degeneration * 1  0/348 (0.00%)  1/344 (0.29%) 
Syncope * 1  2/348 (0.57%)  0/344 (0.00%) 
Product Issues     
Device dislocation * 1  1/348 (0.29%)  3/344 (0.87%) 
Device malfunction * 1  1/348 (0.29%)  0/344 (0.00%) 
Embedded device * 1  0/348 (0.00%)  1/344 (0.29%) 
Psychiatric disorders     
Confusional state * 1  3/348 (0.86%)  0/344 (0.00%) 
Delirium * 1  1/348 (0.29%)  1/344 (0.29%) 
Suicidal ideation * 1  0/348 (0.00%)  1/344 (0.29%) 
Suicide attempt * 1  0/348 (0.00%)  1/344 (0.29%) 
Renal and urinary disorders     
Acute kidney injury * 1  12/348 (3.45%)  12/344 (3.49%) 
Hydronephrosis * 1  1/348 (0.29%)  0/344 (0.00%) 
Nephritis * 1  1/348 (0.29%)  0/344 (0.00%) 
Oliguria * 1  0/348 (0.00%)  1/344 (0.29%) 
Renal disorder * 1  1/348 (0.29%)  0/344 (0.00%) 
Renal failure * 1  0/348 (0.00%)  4/344 (1.16%) 
Renal tubular necrosis * 1  1/348 (0.29%)  0/344 (0.00%) 
Urinary retention * 1  0/348 (0.00%)  1/344 (0.29%) 
Reproductive system and breast disorders     
Scrotal oedema * 1  0/348 (0.00%)  1/344 (0.29%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  1/348 (0.29%)  0/344 (0.00%) 
Acute respiratory failure * 1  2/348 (0.57%)  1/344 (0.29%) 
Asphyxia * 1  1/348 (0.29%)  2/344 (0.58%) 
Aspiration * 1  1/348 (0.29%)  1/344 (0.29%) 
Atelectasis * 1  0/348 (0.00%)  1/344 (0.29%) 
Chronic obstructive pulmonary disease * 1  0/348 (0.00%)  1/344 (0.29%) 
Cough * 1  0/348 (0.00%)  1/344 (0.29%) 
Dyspnoea * 1  5/348 (1.44%)  7/344 (2.03%) 
Haemoptysis * 1  2/348 (0.57%)  3/344 (0.87%) 
Hypoxia * 1  1/348 (0.29%)  3/344 (0.87%) 
Laryngeal haemorrhage * 1  0/348 (0.00%)  1/344 (0.29%) 
Laryngeal inflammation * 1  2/348 (0.57%)  0/344 (0.00%) 
Laryngeal necrosis * 1  0/348 (0.00%)  1/344 (0.29%) 
Laryngeal oedema * 1  4/348 (1.15%)  4/344 (1.16%) 
Laryngeal stenosis * 1  2/348 (0.57%)  0/344 (0.00%) 
Obstructive airways disorder * 1  0/348 (0.00%)  1/344 (0.29%) 
Oropharyngeal pain * 1  1/348 (0.29%)  2/344 (0.58%) 
Pharyngeal haemorrhage * 1  2/348 (0.57%)  2/344 (0.58%) 
Pharyngeal inflammation * 1  2/348 (0.57%)  0/344 (0.00%) 
Pharyngeal necrosis * 1  1/348 (0.29%)  0/344 (0.00%) 
Pharyngeal oedema * 1  1/348 (0.29%)  0/344 (0.00%) 
Pharyngeal stenosis * 1  1/348 (0.29%)  0/344 (0.00%) 
Pharyngeal ulceration * 1  2/348 (0.57%)  0/344 (0.00%) 
Pneumonia aspiration * 1  5/348 (1.44%)  5/344 (1.45%) 
Pneumonitis * 1  6/348 (1.72%)  1/344 (0.29%) 
Pneumothorax * 1  1/348 (0.29%)  2/344 (0.58%) 
Productive cough * 1  1/348 (0.29%)  1/344 (0.29%) 
Pulmonary embolism * 1  2/348 (0.57%)  0/344 (0.00%) 
Respiratory arrest * 1  0/348 (0.00%)  1/344 (0.29%) 
Respiratory distress * 1  2/348 (0.57%)  1/344 (0.29%) 
Respiratory failure * 1  0/348 (0.00%)  2/344 (0.58%) 
Respiratory tract oedema * 1  1/348 (0.29%)  0/344 (0.00%) 
Stridor * 1  2/348 (0.57%)  1/344 (0.29%) 
Tonsillar haemorrhage * 1  1/348 (0.29%)  0/344 (0.00%) 
Tracheal stenosis * 1  1/348 (0.29%)  1/344 (0.29%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme * 1  1/348 (0.29%)  0/344 (0.00%) 
Rash * 1  1/348 (0.29%)  0/344 (0.00%) 
Surgical and medical procedures     
Gastrostomy * 1  1/348 (0.29%)  0/344 (0.00%) 
Vascular disorders     
Capillary leak syndrome * 1  0/348 (0.00%)  1/344 (0.29%) 
Circulatory collapse * 1  0/348 (0.00%)  1/344 (0.29%) 
Embolism * 1  1/348 (0.29%)  0/344 (0.00%) 
Haematoma * 1  0/348 (0.00%)  1/344 (0.29%) 
Haemorrhage * 1  1/348 (0.29%)  1/344 (0.29%) 
Hypotension * 1  2/348 (0.57%)  4/344 (1.16%) 
Lymphorrhoea * 1  0/348 (0.00%)  1/344 (0.29%) 
Phlebitis superficial * 1  1/348 (0.29%)  0/344 (0.00%) 
Shock * 1  1/348 (0.29%)  0/344 (0.00%) 
Vascular rupture * 1  1/348 (0.29%)  0/344 (0.00%) 
Vasculitis * 1  1/348 (0.29%)  0/344 (0.00%) 
Venous haemorrhage * 1  0/348 (0.00%)  1/344 (0.29%) 
1
Term from vocabulary, MedDRA Version 22.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Avelumab + Standard of Care Chemotherapy (SOC CRT) Placebo + SOC CRT
Affected / at Risk (%) Affected / at Risk (%)
Total   344/348 (98.85%)   340/344 (98.84%) 
Blood and lymphatic system disorders     
Anaemia * 1  205/348 (58.91%)  192/344 (55.81%) 
Leukopenia * 1  64/348 (18.39%)  46/344 (13.37%) 
Lymphopenia * 1  33/348 (9.48%)  27/344 (7.85%) 
Neutropenia * 1  102/348 (29.31%)  98/344 (28.49%) 
Thrombocytopenia * 1  45/348 (12.93%)  41/344 (11.92%) 
Ear and labyrinth disorders     
Ear pain * 1  23/348 (6.61%)  12/344 (3.49%) 
Hypoacusis * 1  29/348 (8.33%)  29/344 (8.43%) 
Tinnitus * 1  59/348 (16.95%)  65/344 (18.90%) 
Endocrine disorders     
Hyperthyroidism * 1  24/348 (6.90%)  7/344 (2.03%) 
Hypothyroidism * 1  51/348 (14.66%)  43/344 (12.50%) 
Gastrointestinal disorders     
Abdominal pain * 1  11/348 (3.16%)  20/344 (5.81%) 
Abdominal pain upper * 1  14/348 (4.02%)  18/344 (5.23%) 
Constipation * 1  178/348 (51.15%)  154/344 (44.77%) 
Diarrhoea * 1  83/348 (23.85%)  66/344 (19.19%) 
Dry mouth * 1  151/348 (43.39%)  157/344 (45.64%) 
Dyspepsia * 1  23/348 (6.61%)  21/344 (6.10%) 
Dysphagia * 1  143/348 (41.09%)  152/344 (44.19%) 
Nausea * 1  210/348 (60.34%)  199/344 (57.85%) 
Odynophagia * 1  62/348 (17.82%)  48/344 (13.95%) 
Oral pain * 1  39/348 (11.21%)  43/344 (12.50%) 
Stomatitis * 1  93/348 (26.72%)  96/344 (27.91%) 
Vomiting * 1  112/348 (32.18%)  121/344 (35.17%) 
General disorders     
Asthenia * 1  63/348 (18.10%)  57/344 (16.57%) 
Chills * 1  39/348 (11.21%)  7/344 (2.03%) 
Fatigue * 1  116/348 (33.33%)  127/344 (36.92%) 
Localised oedema * 1  22/348 (6.32%)  20/344 (5.81%) 
Malaise * 1  20/348 (5.75%)  23/344 (6.69%) 
Mucosal inflammation * 1  146/348 (41.95%)  130/344 (37.79%) 
Oedema peripheral * 1  19/348 (5.46%)  16/344 (4.65%) 
Pain * 1  23/348 (6.61%)  28/344 (8.14%) 
Pyrexia * 1  87/348 (25.00%)  44/344 (12.79%) 
Infections and infestations     
Oral candidiasis * 1  25/348 (7.18%)  31/344 (9.01%) 
Pneumonia * 1  36/348 (10.34%)  25/344 (7.27%) 
Upper respiratory tract infection * 1  24/348 (6.90%)  20/344 (5.81%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  24/348 (6.90%)  6/344 (1.74%) 
Radiation skin injury * 1  135/348 (38.79%)  136/344 (39.53%) 
Investigations     
Alanine aminotransferase increased * 1  56/348 (16.09%)  30/344 (8.72%) 
Amylase increased * 1  22/348 (6.32%)  10/344 (2.91%) 
Aspartate aminotransferase increased * 1  55/348 (15.80%)  24/344 (6.98%) 
Blood alkaline phosphatase increased * 1  22/348 (6.32%)  9/344 (2.62%) 
Blood creatinine increased * 1  88/348 (25.29%)  73/344 (21.22%) 
Blood urea increased * 1  18/348 (5.17%)  17/344 (4.94%) 
Gamma-glutamyltransferase increased * 1  22/348 (6.32%)  15/344 (4.36%) 
Lymphocyte count decreased * 1  41/348 (11.78%)  43/344 (12.50%) 
Neutrophil count decreased * 1  64/348 (18.39%)  60/344 (17.44%) 
Platelet count decreased * 1  40/348 (11.49%)  33/344 (9.59%) 
Weight decreased * 1  157/348 (45.11%)  170/344 (49.42%) 
White blood cell count decreased * 1  69/348 (19.83%)  64/344 (18.60%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  128/348 (36.78%)  124/344 (36.05%) 
Dehydration * 1  31/348 (8.91%)  29/344 (8.43%) 
Hyperglycaemia * 1  31/348 (8.91%)  33/344 (9.59%) 
Hyperkalaemia * 1  34/348 (9.77%)  32/344 (9.30%) 
Hypoalbuminaemia * 1  42/348 (12.07%)  36/344 (10.47%) 
Hypocalcaemia * 1  28/348 (8.05%)  23/344 (6.69%) 
Hypokalaemia * 1  87/348 (25.00%)  71/344 (20.64%) 
Hypomagnesaemia * 1  92/348 (26.44%)  84/344 (24.42%) 
Hyponatraemia * 1  83/348 (23.85%)  67/344 (19.48%) 
Hypophosphataemia * 1  23/348 (6.61%)  32/344 (9.30%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  17/348 (4.89%)  20/344 (5.81%) 
Neck pain * 1  30/348 (8.62%)  25/344 (7.27%) 
Nervous system disorders     
Dizziness * 1  41/348 (11.78%)  33/344 (9.59%) 
Dysgeusia * 1  106/348 (30.46%)  119/344 (34.59%) 
Headache * 1  44/348 (12.64%)  40/344 (11.63%) 
Neuropathy peripheral * 1  11/348 (3.16%)  28/344 (8.14%) 
Psychiatric disorders     
Anxiety * 1  26/348 (7.47%)  34/344 (9.88%) 
Depression * 1  10/348 (2.87%)  18/344 (5.23%) 
Insomnia * 1  56/348 (16.09%)  44/344 (12.79%) 
Renal and urinary disorders     
Acute kidney injury * 1  18/348 (5.17%)  22/344 (6.40%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  73/348 (20.98%)  63/344 (18.31%) 
Dysphonia * 1  51/348 (14.66%)  47/344 (13.66%) 
Dyspnoea * 1  32/348 (9.20%)  31/344 (9.01%) 
Hiccups * 1  26/348 (7.47%)  23/344 (6.69%) 
Oropharyngeal pain * 1  75/348 (21.55%)  91/344 (26.45%) 
Pharyngeal inflammation * 1  24/348 (6.90%)  23/344 (6.69%) 
Productive cough * 1  39/348 (11.21%)  31/344 (9.01%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  22/348 (6.32%)  20/344 (5.81%) 
Dermatitis * 1  52/348 (14.94%)  42/344 (12.21%) 
Dry skin * 1  18/348 (5.17%)  24/344 (6.98%) 
Erythema * 1  24/348 (6.90%)  27/344 (7.85%) 
Pruritus * 1  38/348 (10.92%)  24/344 (6.98%) 
Rash * 1  43/348 (12.36%)  35/344 (10.17%) 
Vascular disorders     
Hypertension * 1  32/348 (9.20%)  28/344 (8.14%) 
Hypotension * 1  22/348 (6.32%)  14/344 (4.07%) 
Lymphoedema * 1  18/348 (5.17%)  15/344 (4.36%) 
1
Term from vocabulary, MedDRA Version 22.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02952586    
Other Study ID Numbers: B9991016
2016-001456-21 ( EudraCT Number )
LOCALLY ADVANCED HEAD AND NECK ( Other Identifier: Alias Study Number )
First Submitted: October 31, 2016
First Posted: November 2, 2016
Results First Submitted: December 21, 2020
Results First Posted: February 24, 2021
Last Update Posted: June 22, 2021