Squamous Cell Carcinoma of the Head and Neck
Conditions
Brief summary
This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.
Interventions
DRUGAvelumab
Avelumab + SOC Chemoradiation
OTHERChemoradiation
Cisplatin + Radiation Therapy
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx * HPV negative disease, Stage III, IVa, IVb; non-oropharyngeal HPV positive disease Stage III, IVa, IVb, HPV positive oropharyngeal disease T4 or N2c or N3 * No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative intent. * Available tumor samples for submission or willing to undergo further tumor biopsies: * Age ≥18 years (≥19 in Korea;20 years in Japan and Taiwan). * ECOG Performance Status 0 or 1 * Adequate bone marrow function * Adequate renal function * Adequate liver function * Pregnancy test (for patients of childbearing potential) negative at screening
Exclusion criteria
* Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways. * Major surgery 4 weeks prior to randomization. * Prior malignancy requiring tumor-directed therapy within the last 2 years prior to enrollment, or concurrent malignancy associated with clinical instability. Exceptions for disease within the 2 years are superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score 6) either curatively treated or deemed to not require treatment, ductal IS carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer. * Active autoimmune disease * Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. * Active infection requiring systemic therapy. * Use of immunosuppressive medication at time of randomization * Prior organ transplantation including allogenic stem-cell transplantation. * Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. * Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection * Vaccination within 4 weeks prior to randomization. * Current use of or anticipated need for treatment with other anti-cancer drugs. * Pregnant female patients, breastfeeding female patients, and male patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator | From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months) | PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (\>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site | From randomization until PD or death (up to 37 months) | pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site. |
| Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator | From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months) | Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method. |
| Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator | From randomization until disease progression or death, whichever occurred first (up to 37 months) | Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than \[\<\] 10 millimeter \[mm\]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (\<10 mm short axis) . PR: Greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized. |
| Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator | From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months) | Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method. |
| Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator | From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months) | DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:\>=30% decrease under baseline of sum of diameters of all target measurable lesions. CR for target disease:complete disappearance of all target lesions with exception of nodal disease.CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. PD is any of following:1)Locoregional PD confirmed by pathology to verify radiographic changes denote true tumor progression and not radiation effects or non-malignant contrast enhancement.2)Locoregional clinically detectable progression confirmed by pathology.3)Surgical removal of primary tumor with tumor present on final pathology.4)Salvage neck dissection \>20 weeks after completion of CRT with tumor present on final pathology.5)Metastatic PD. DOR data was censored on date of last adequate tumor assessment for participants with no overall response. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Baseline up to 44 months | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period. |
| Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Baseline up to 15 months | Grade 1 and 3 ranges are: Anemia:Hb:\<LLN-10.0,\<8.0 g/dL;LC decreased (dec):\<LLN-800/mm\^3,500-200/mm\^3;LC increased (inc):grade 3:\>20,000/mm\^3:NC dec:\<LLN-1500/mm\^3;\<1000-500/mm\^3;PC dec:\<LLN-75,000/mm\^3;\<50,000-25,000/mm\^3;WBC dec:\<LLN-3000/mm\^3;\<2000-1000/mm\^3;ALT inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;ALP & GGT inc:\>ULN-2.5\*ULN;\>5.0-20.0\*ULN;AST inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;BB inc:\>ULN-1.5\*ULN;\>3.0-10.0\*ULN;CH high:\>ULN-300 mg/dL;\>400-500 mg/dL;CPK inc:\>ULN-2.5\*ULN;\>5\*ULN-10\*ULN;Hypercalcemia:\>ULN-11.5;\>12.5-13.5mg/dL;Hyperglycemia:\>ULN-160; \>250-500mg/dL;Hyperkalemia:\>ULN-5.5;\>6.0-7.0mmol/L;Hypermagnesemia:\>ULN-3.0;\>3.0-8.0 mg/dL;Hypernatremia:\>ULN-150; \>155-160 mmol/L;Hypertriglyceridemia;150-300;\>500-1000 mg/dL;Hypoalbuminemia:\<LLN-3;\<2g/dL;Hypocalcemia:\<LLN-8.0;\<8.0-7.0mg/dL;Hypokalemia:\<LLN-3.0;\<3.0-2.5mmol/L;Hypomagnesemia;\<LLN-1.2;\<0.9-0.7 mg/dL;Hyponatremia:\<LLN-130;\<130-120mmol/L; Hypophosphatemia:\<LLN-2.5;\<2.0-1.0mg/dL;lipase & serum amylase inc:\>ULN-1.5\*ULN;\>2.0-5.0\*ULN. |
| Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug) | Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported. |
| Change From Baseline in Vital Sign - Pulse Rate | Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug) | Change from baseline in pulse rate in sitting position in beats per minute was reported. |
| Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) | EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. |
| Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) | EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. |
| Overall Survival (OS) | From randomization to the date of death or censored date, whichever occurred first (up to 37 months) | Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method. |
| Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) | Baseline (prior to first dose) | PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells. |
| Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells | Baseline (prior to first dose) | Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm\^2). |
| Percentage of Participants With Positive and Negative Pathology of Neck Dissection | From randomization until PD as per investigator assessment (up to 37 months) | Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study. |
| Maximum Plasma Concentration (Cmax) of Avelumab | Pre-dose and end of infusion on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1 and 2 (each cycle 28 days) | Maximum observed plasma concentration (Cmax) of Avelumab is reported. |
| Predose Plasma Concentration (Ctrough) of Avelumab | Pre-dose on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1, 2, 5, 8, 11 (each cycle 28 days) | Ctrough refers to plasma concentration of Avelumab observed just before treatment administration. |
| Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin | Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase | Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of total and free Cisplastin (in mg) administered to a participant. |
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin | Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase | Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). AUClast (dn) was calculated by dividing AUClast by the exact dose of cisplastin (in mg) administered to a participant. |
| Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin | Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase | Maximum observed plasma concentration (Cmax) of total and free Cisplatin is reported. |
| Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin | Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase | Time to reach maximum observed plasma concentration (Tmax) of total and free Cisplatin. |
| Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status | pre-dose on Day 1 up to 30 Days after the end of treatment | ADA never-positive was defined as no positive ADA results at any time point; ADA-negative participants (titer less than\< cut point) and ADA ever-positive was defined as at least one positive ADA result at any time point; ADA-positive participants (titer greater than or equal to cut point) |
| Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status | Day 1 of lead-in phase and on Days 8 and 25 of CRT phase | — |
| Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) | The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning. |
Countries
Australia, Austria, Belgium, Canada, China, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Poland, Portugal, Russia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Study had 3 sequential treatment phases: Lead-in, CRT, and Maintenance. There were 3 treatments administered in parallel during CRT phase: Avelumab, Cisplatin and IMRT.
Pre-assignment details
Study had 3 sequential treatment phases: Lead-in, CRT, and Maintenance. There were 3 treatments administered during CRT phase: Avelumab, Cisplatin and IMRT. Reasons for discontinuation of each treatment are summarized separately. 11 participants discontinued all 3 treatments during CRT phase due to death. Two patients discontinued cisplatin due to adverse event and subsequently discontinued avelumab and IMRT due to death.
Participants by arm
| Arm | Count |
|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) Participants with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were administered with avelumab 10 milligram per kilogram (mg/kg) intravenous (IV) injection on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin 100 milligram per square meter (mg/m\^2) on Days 1, 22, 43 and intensity-modulated radiation therapy (IMRT) 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received avelumab 10 mg/kg IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term (LT) follow up period every 16 weeks for survival and new systemic anticancer treatment. | 350 |
| Placebo + SOC CRT Participants with LA SCCHN were administered with placebo IV injection matched to avelumab on Day 1 of the Lead-in Phase (7 days) and on Days 8, 25 and 39 in CRT phase (63 days). In CRT phase participants also received SOC CRT: cisplatin mg/m\^2 on Days 1, 22 and 43 + IMRT 5 days a week. CRT phase was followed by maintenance phase (12 months) in which participants received placebo IV injection every 2 weeks. All participants were followed for safety 30 days after the last study treatment administration or until the time of initiation of new systemic anticancer treatment. If any concern arose participants were followed up on Day 90 via telephone call thereafter in long term follow up period every 16 weeks for survival and new systemic anticancer treatment. | 347 |
| Total | 697 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| CRT for Avelumab or Placebo (63 Days) | Adverse Event | 12 | 12 |
| CRT for Avelumab or Placebo (63 Days) | Death | 5 | 8 |
| CRT for Avelumab or Placebo (63 Days) | Global Deterioration of Health Status | 1 | 0 |
| CRT for Avelumab or Placebo (63 Days) | Lost to Follow-up | 1 | 1 |
| CRT for Avelumab or Placebo (63 Days) | Other | 2 | 1 |
| CRT for Avelumab or Placebo (63 Days) | Physician Decision | 2 | 1 |
| CRT for Avelumab or Placebo (63 Days) | Withdrawal by Subject | 10 | 4 |
| CRT for Cisplatin (63 Days) | Adverse Event | 82 | 81 |
| CRT for Cisplatin (63 Days) | Death | 3 | 8 |
| CRT for Cisplatin (63 Days) | Global Deterioration of Health Status | 1 | 0 |
| CRT for Cisplatin (63 Days) | Lost to Follow-up | 1 | 1 |
| CRT for Cisplatin (63 Days) | Other | 1 | 1 |
| CRT for Cisplatin (63 Days) | Physician Decision | 12 | 10 |
| CRT for Cisplatin (63 Days) | Withdrawal by Subject | 11 | 3 |
| CRT for IMRT (63 Days) | Adverse Event | 5 | 5 |
| CRT for IMRT (63 Days) | Death | 5 | 8 |
| CRT for IMRT (63 Days) | Global Deterioration of Health Status | 1 | 0 |
| CRT for IMRT (63 Days) | Lost to Follow-up | 1 | 1 |
| CRT for IMRT (63 Days) | Other | 1 | 0 |
| CRT for IMRT (63 Days) | Withdrawal by Subject | 10 | 6 |
| Follow-Up Phase (90 Days) | Death | 12 | 10 |
| Follow-Up Phase (90 Days) | Lost to Follow-up | 1 | 1 |
| Follow-Up Phase (90 Days) | Other | 7 | 5 |
| Follow-Up Phase (90 Days) | Study Terminated by Sponsor | 32 | 50 |
| Follow-Up Phase (90 Days) | Withdrawal by Subject | 6 | 2 |
| Lead-In Phase (7 Days) | Adverse Event | 3 | 0 |
| Lead-In Phase (7 Days) | Death | 0 | 1 |
| Lead-In Phase (7 Days) | No Longer Met Eligibility Criteria | 0 | 1 |
| Lead-In Phase (7 Days) | Withdrawal by Subject | 2 | 2 |
| LT Follow-up (up to 45 Months) | Death | 51 | 31 |
| LT Follow-up (up to 45 Months) | Lost to Follow-up | 2 | 4 |
| LT Follow-up (up to 45 Months) | Study Terminated by Sponsor | 187 | 201 |
| LT Follow-up (up to 45 Months) | Withdrawal by Subject | 7 | 1 |
| Maintenance Phase (12 Months) | Adverse Event | 24 | 21 |
| Maintenance Phase (12 Months) | Death | 17 | 11 |
| Maintenance Phase (12 Months) | Global Deterioration of Health Status | 14 | 5 |
| Maintenance Phase (12 Months) | Lost to Follow-up | 1 | 2 |
| Maintenance Phase (12 Months) | Non-compliance With Study Drug | 1 | 1 |
| Maintenance Phase (12 Months) | Other | 2 | 1 |
| Maintenance Phase (12 Months) | Physician Decision | 1 | 1 |
| Maintenance Phase (12 Months) | Progressive disease | 60 | 54 |
| Maintenance Phase (12 Months) | Study Terminated by Sponsor | 1 | 6 |
| Maintenance Phase (12 Months) | Withdrawal by Subject | 31 | 25 |
Baseline characteristics
| Characteristic | Avelumab + Standard of Care Chemotherapy (SOC CRT) | Placebo + SOC CRT | Total |
|---|---|---|---|
| Age, Continuous | 59.36 years STANDARD_DEVIATION 8.56 | 58.88 years STANDARD_DEVIATION 9.09 | 59.12 years STANDARD_DEVIATION 8.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 8 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 312 Participants | 312 Participants | 624 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants | 27 Participants | 52 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 102 Participants | 86 Participants | 188 Participants |
| Race/Ethnicity, Customized Black or African American | 9 Participants | 10 Participants | 19 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 14 Participants | 21 Participants | 35 Participants |
| Race/Ethnicity, Customized White | 224 Participants | 229 Participants | 453 Participants |
| Sex: Female, Male Female | 60 Participants | 62 Participants | 122 Participants |
| Sex: Female, Male Male | 290 Participants | 285 Participants | 575 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 86 / 348 | 62 / 344 |
| other Total, other adverse events | 344 / 348 | 340 / 344 |
| serious Total, serious adverse events | 184 / 348 | 177 / 344 |
Outcome results
Primary
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator
PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (\>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event.
Time frame: From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator | NA months |
| Placebo + SOC CRT | Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator | NA months |
p-value: 0.919995% CI: [0.928, 1.573]Log Rank
Secondary
Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase
The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning.
Time frame: Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | Baseline | 60.56 units on a scale | Standard Deviation 13.731 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 1 | -0.59 units on a scale | Standard Deviation 8.719 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 29 | -14.34 units on a scale | Standard Deviation 16.847 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle1/Day1 | -11.33 units on a scale | Standard Deviation 16.054 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle3/Day1 | -3.81 units on a scale | Standard Deviation 14.017 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle7/Day1 | -0.86 units on a scale | Standard Deviation 12.503 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle7/Day15 | 3.96 units on a scale | Standard Deviation 14.035 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle11/Day1 | 2.68 units on a scale | Standard Deviation 13.367 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle11/Day15 | 3.96 units on a scale | Standard Deviation 14.322 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at End of treatment | -2.35 units on a scale | Standard Deviation 17.428 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle11/Day1 | 4.90 units on a scale | Standard Deviation 14.207 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | Baseline | 61.05 units on a scale | Standard Deviation 13.155 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle7/Day1 | -0.51 units on a scale | Standard Deviation 14.585 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 1 | -0.14 units on a scale | Standard Deviation 9.136 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at End of treatment | 0.79 units on a scale | Standard Deviation 16.509 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 29 | -14.56 units on a scale | Standard Deviation 15.47 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle7/Day15 | 0.92 units on a scale | Standard Deviation 14.454 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle1/Day1 | -12.08 units on a scale | Standard Deviation 14.95 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle11/Day15 | 3.37 units on a scale | Standard Deviation 12.689 |
| Placebo + SOC CRT | Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase | CRT Phase: Change at Cycle3/Day1 | -2.26 units on a scale | Standard Deviation 13.625 |
Secondary
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Time frame: Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)
Population: FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 29 | -0.0915 units on a scale | Standard Deviation 0.22053 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 1 | -0.0078 units on a scale | Standard Deviation 0.13269 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day15 | 0.0552 units on a scale | Standard Deviation 0.18544 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle1/Day1 | -0.0749 units on a scale | Standard Deviation 0.22126 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day1 | 0.0376 units on a scale | Standard Deviation 0.21078 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Baseline | 0.7718 units on a scale | Standard Deviation 0.17822 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day15 | 0.0673 units on a scale | Standard Deviation 0.17227 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle3/Day1 | -0.0203 units on a scale | Standard Deviation 0.2134 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at End of treatment | -0.0051 units on a scale | Standard Deviation 0.24528 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day1 | 0.0088 units on a scale | Standard Deviation 0.1669 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at End of treatment | 0.0074 units on a scale | Standard Deviation 0.24874 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Baseline | 0.7615 units on a scale | Standard Deviation 0.18517 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 1 | 0.0176 units on a scale | Standard Deviation 0.14066 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 29 | -0.0487 units on a scale | Standard Deviation 0.19175 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle1/Day1 | -0.0519 units on a scale | Standard Deviation 0.17253 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle3/Day1 | -0.0160 units on a scale | Standard Deviation 0.18179 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day1 | 0.0140 units on a scale | Standard Deviation 0.1624 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day15 | 0.0472 units on a scale | Standard Deviation 0.1799 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day1 | 0.0792 units on a scale | Standard Deviation 0.19287 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day15 | 0.0389 units on a scale | Standard Deviation 0.18732 |
Secondary
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status.
Time frame: Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug)
Population: FAS included all randomized participants. FAS included all randomized participants. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 29 | -10.9 units on a scale | Standard Deviation 19.94 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Baseline | 75.8 units on a scale | Standard Deviation 18.2 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 1 | -1.1 units on a scale | Standard Deviation 13.49 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle1/Day1 | -7.7 units on a scale | Standard Deviation 19.05 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle3/Day1 | -1.8 units on a scale | Standard Deviation 18 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day1 | -0.6 units on a scale | Standard Deviation 14.91 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day15 | 4.8 units on a scale | Standard Deviation 18.52 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day1 | 0.3 units on a scale | Standard Deviation 17.6 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day15 | 10.1 units on a scale | Standard Deviation 24.69 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at End of treatment | -1.9 units on a scale | Standard Deviation 22.55 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day1 | 4.3 units on a scale | Standard Deviation 16.1 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day1 | 8.6 units on a scale | Standard Deviation 81.42 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Baseline | 74.9 units on a scale | Standard Deviation 18.24 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at End of treatment | 0.7 units on a scale | Standard Deviation 19.28 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 1 | -1.4 units on a scale | Standard Deviation 11.39 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | CRT Phase: Change at Day 29 | -9.2 units on a scale | Standard Deviation 18.7 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle7/Day15 | 3.1 units on a scale | Standard Deviation 19.28 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle1/Day1 | -6.2 units on a scale | Standard Deviation 18.67 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle11/Day15 | 2.4 units on a scale | Standard Deviation 18.2 |
| Placebo + SOC CRT | Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase | Maintenance Phase: Change at Cycle3/Day1 | -0.7 units on a scale | Standard Deviation 16.14 |
Secondary
Change From Baseline in Vital Sign - Pulse Rate
Change from baseline in pulse rate in sitting position in beats per minute was reported.
Time frame: Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)
Population: Safety analysis set included all participants who received at least one dose of study drug. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle13/Day 15 | -1.3 beats per minute | Standard Deviation 15.57 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle7/Day 1 | -0.1 beats per minute | Standard Deviation 14.47 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Baseline | 79.9 beats per minute | Standard Deviation 13.72 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle9/Day 15 | -1.0 beats per minute | Standard Deviation 14.2 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Lead in Phase: Change at Day 1 | -3.5 beats per minute | Standard Deviation 0.71 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle5/Day 1 | 2.6 beats per minute | Standard Deviation 13.88 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 1 | 0.7 beats per minute | Standard Deviation 11.7 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle10/Day 1 | -0.9 beats per minute | Standard Deviation 13.4 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 8 | 1.5 beats per minute | Standard Deviation 13.15 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle7/Day 15 | -0.1 beats per minute | Standard Deviation 14.24 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 22 | 0.5 beats per minute | Standard Deviation 13.86 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle10/Day 15 | -0.5 beats per minute | Standard Deviation 15.33 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 25 | -1.6 beats per minute | Standard Deviation 14.87 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle6/Day 1 | 1.6 beats per minute | Standard Deviation 15.42 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 29 | -11.0 beats per minute | Standard Deviation 20.47 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle11/Day 1 | -1.6 beats per minute | Standard Deviation 14.57 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 39 | 4.0 beats per minute | Standard Deviation 15.46 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle8/Day 1 | -0.2 beats per minute | Standard Deviation 13.84 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 43 | 4.7 beats per minute | Standard Deviation 16.82 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle11/Day 15 | -0.2 beats per minute | Standard Deviation 13.23 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle1/Day 1 | 5.1 beats per minute | Standard Deviation 16.23 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle6/Day 15 | 0.4 beats per minute | Standard Deviation 14.04 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle1/Day 15 | 3.8 beats per minute | Standard Deviation 15.04 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle12/Day 1 | -0.3 beats per minute | Standard Deviation 13.92 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle2/Day 1 | 3.5 beats per minute | Standard Deviation 15.3 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle8/Day 15 | -1.5 beats per minute | Standard Deviation 14.52 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle2/Day 15 | 4.1 beats per minute | Standard Deviation 15.32 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle12/Day 15 | -1.4 beats per minute | Standard Deviation 14.92 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle3/Day 1 | 3.5 beats per minute | Standard Deviation 14.49 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle5/Day 15 | 1.6 beats per minute | Standard Deviation 15.11 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle3/Day 15 | 2.8 beats per minute | Standard Deviation 14.73 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle13/Day 1 | -1.4 beats per minute | Standard Deviation 14.09 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle4/Day 1 | 1.8 beats per minute | Standard Deviation 14.79 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle9/Day 1 | -1.0 beats per minute | Standard Deviation 14.29 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle4/Day 15 | 1.6 beats per minute | Standard Deviation 14.8 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Pulse Rate | EOT | 0.2 beats per minute | Standard Deviation 14.73 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle4/Day 15 | 3.8 beats per minute | Standard Deviation 15.02 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | EOT | 1.9 beats per minute | Standard Deviation 14.09 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle6/Day 1 | 2.7 beats per minute | Standard Deviation 15.72 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle5/Day 1 | 2.9 beats per minute | Standard Deviation 14.82 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle5/Day 15 | 3.3 beats per minute | Standard Deviation 13.74 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle6/Day 15 | 1.4 beats per minute | Standard Deviation 13.66 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle7/Day 1 | 2.5 beats per minute | Standard Deviation 14.18 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle7/Day 15 | 1.4 beats per minute | Standard Deviation 14.33 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle8/Day 1 | 1.0 beats per minute | Standard Deviation 13.67 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle8/Day 15 | 1.5 beats per minute | Standard Deviation 14.86 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle9/Day 1 | -0.1 beats per minute | Standard Deviation 14.06 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle9/Day 15 | 0.2 beats per minute | Standard Deviation 14.44 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle10/Day 1 | 0.7 beats per minute | Standard Deviation 14.52 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle10/Day 15 | 0.7 beats per minute | Standard Deviation 14.66 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle11/Day 1 | 0.2 beats per minute | Standard Deviation 14.01 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle11/Day 15 | 0.3 beats per minute | Standard Deviation 12.93 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle12/Day 1 | 0.4 beats per minute | Standard Deviation 13.67 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle12/Day 15 | -0.5 beats per minute | Standard Deviation 12.47 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle13/Day 1 | -0.1 beats per minute | Standard Deviation 12.22 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle13/Day 15 | 0.4 beats per minute | Standard Deviation 13.24 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Baseline | 86.0 beats per minute | Standard Deviation 43 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Lead in Phase: Change at Day 1 | -8.5 beats per minute | Standard Deviation 19.09 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 1 | 1.3 beats per minute | Standard Deviation 10.92 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 8 | 2.2 beats per minute | Standard Deviation 12.42 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 22 | 2.6 beats per minute | Standard Deviation 12.24 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 25 | -1.2 beats per minute | Standard Deviation 13.9 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 29 | 3.6 beats per minute | Standard Deviation 21.29 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 39 | 4.3 beats per minute | Standard Deviation 14.71 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | CRT Phase: Change at Day 43 | 6.1 beats per minute | Standard Deviation 14.78 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle1/Day 1 | 7.5 beats per minute | Standard Deviation 14.43 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle1/Day 15 | 6.3 beats per minute | Standard Deviation 13.65 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle2/Day 1 | 5.9 beats per minute | Standard Deviation 14.74 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle2/Day 15 | 4.9 beats per minute | Standard Deviation 13.94 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle3/Day 1 | 3.9 beats per minute | Standard Deviation 14.37 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle3/Day 15 | 2.8 beats per minute | Standard Deviation 14.14 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Pulse Rate | Maintenance Phase: Change at Cycle4/Day 1 | 3.8 beats per minute | Standard Deviation 14.95 |
Secondary
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure
Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported.
Time frame: Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug)
Population: Safety analysis set included all participants who received at least one dose of study drug. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number analyzed signifies participants evaluable for each specified category at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 39 | -10.6 millimeter of mercury | Standard Deviation 20.51 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle13/Day 1 | -2.0 millimeter of mercury | Standard Deviation 9.6 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle4/Day 1 | -2.2 millimeter of mercury | Standard Deviation 12.07 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle13/Day 15 | -1.1 millimeter of mercury | Standard Deviation 10.22 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 22 | -4.2 millimeter of mercury | Standard Deviation 11.77 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | DBP: EOT | -2.4 millimeter of mercury | Standard Deviation 11.96 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle4/Day 15 | -2.4 millimeter of mercury | Standard Deviation 11.38 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Lead in Phase: SBP: Change at Day 1 | -5.5 millimeter of mercury | Standard Deviation 2.12 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 25 | -3.4 millimeter of mercury | Standard Deviation 11.91 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 1 | -2.5 millimeter of mercury | Standard Deviation 15.32 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle5/Day 1 | -2.8 millimeter of mercury | Standard Deviation 11.61 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 8 | -8.3 millimeter of mercury | Standard Deviation 17.78 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | SBP: EOT | -7.0 millimeter of mercury | Standard Deviation 19.83 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 22 | -8.9 millimeter of mercury | Standard Deviation 18.54 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle5/Day 15 | -2.5 millimeter of mercury | Standard Deviation 11.89 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 43 | -9.6 millimeter of mercury | Standard Deviation 18.53 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | DBP: Baseline | 77.8 millimeter of mercury | Standard Deviation 10.13 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle1/Day 1 | -9.4 millimeter of mercury | Standard Deviation 17.97 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle6/Day 1 | -3.1 millimeter of mercury | Standard Deviation 11.21 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle1/Day 15 | -9.5 millimeter of mercury | Standard Deviation 17.73 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 39 | -5.7 millimeter of mercury | Standard Deviation 11.83 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle2/Day 1 | -7.0 millimeter of mercury | Standard Deviation 18.03 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle6/Day 15 | -3.8 millimeter of mercury | Standard Deviation 12.2 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at /Cycle2/Day 15 | -7.9 millimeter of mercury | Standard Deviation 18.55 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle3/Day 1 | -2.7 millimeter of mercury | Standard Deviation 11.37 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle3/Day 1 | -7.3 millimeter of mercury | Standard Deviation 18.93 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle7/Day 1 | -4.1 millimeter of mercury | Standard Deviation 11.48 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle3/Day 15 | -8.3 millimeter of mercury | Standard Deviation 17.79 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 43 | -5.0 millimeter of mercury | Standard Deviation 11.49 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle4/Day 1 | -8.4 millimeter of mercury | Standard Deviation 18.01 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle7/Day 15 | -3.8 millimeter of mercury | Standard Deviation 12.05 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle4/Day 15 | -6.2 millimeter of mercury | Standard Deviation 18.2 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Lead in Phase: DBP: Change at Day 1 | -3.0 millimeter of mercury | Standard Deviation 4.24 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Maintenance/Cycle5/Day 1 | -7.6 millimeter of mercury | Standard Deviation 17.57 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle8/Day 1 | -2.9 millimeter of mercury | Standard Deviation 11.29 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle5/Day 15 | -8.4 millimeter of mercury | Standard Deviation 18.69 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle1/Day 1 | -4.8 millimeter of mercury | Standard Deviation 11.43 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle6/Day 1 | -7.6 millimeter of mercury | Standard Deviation 17.67 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle8/Day 15 | -3.4 millimeter of mercury | Standard Deviation 11.48 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle6/Day 15 | -7.1 millimeter of mercury | Standard Deviation 19.35 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 25 | -7.9 millimeter of mercury | Standard Deviation 19.06 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle7/Day 1 | -9.0 millimeter of mercury | Standard Deviation 18.3 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle9/Day 1 | -3.1 millimeter of mercury | Standard Deviation 11.78 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle7/Day 15 | -8.7 millimeter of mercury | Standard Deviation 18.1 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle1/Day 15 | -3.7 millimeter of mercury | Standard Deviation 11.78 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle8/Day 1 | -6.5 millimeter of mercury | Standard Deviation 17 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle9/Day 15 | -2.1 millimeter of mercury | Standard Deviation 11.52 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle8/Day 15 | -6.8 millimeter of mercury | Standard Deviation 16.69 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 1 | -1.5 millimeter of mercury | Standard Deviation 9.52 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle9/Day 1 | -6.1 millimeter of mercury | Standard Deviation 18.49 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle10/Day 1 | -2.2 millimeter of mercury | Standard Deviation 11.58 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle9/Day 15 | -6.3 millimeter of mercury | Standard Deviation 19 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle2/Day 1 | -3.3 millimeter of mercury | Standard Deviation 11.74 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle10/Day 1 | -6.1 millimeter of mercury | Standard Deviation 19.24 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle10/Day 15 | -2.5 millimeter of mercury | Standard Deviation 10.9 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle10/Day 15 | -5.6 millimeter of mercury | Standard Deviation 17.07 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | SBP: Baseline | 129.8 millimeter of mercury | Standard Deviation 16.42 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle11/Day 1 | -6.3 millimeter of mercury | Standard Deviation 19.44 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle11/Day 1 | -2.7 millimeter of mercury | Standard Deviation 11.01 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle11/Day 15 | -6.3 millimeter of mercury | Standard Deviation 18.99 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle2/Day 15 | -2.7 millimeter of mercury | Standard Deviation 11.05 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle12/Day 1 | -6.8 millimeter of mercury | Standard Deviation 18.25 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle11/Day 15 | -2.9 millimeter of mercury | Standard Deviation 10.37 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle12/Day 15 | -7.1 millimeter of mercury | Standard Deviation 19.34 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 8 | -3.8 millimeter of mercury | Standard Deviation 10.46 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle13/Day 1 | -5.8 millimeter of mercury | Standard Deviation 20.04 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle12/Day 1 | -2.1 millimeter of mercury | Standard Deviation 9.51 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle13/Day 15 | -4.9 millimeter of mercury | Standard Deviation 18.82 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle3/Day 15 | -2.7 millimeter of mercury | Standard Deviation 11.09 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle12/Day 15 | -3.3 millimeter of mercury | Standard Deviation 11.78 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | SBP: EOT | -4.9 millimeter of mercury | Standard Deviation 17.97 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | DBP: EOT | -3.2 millimeter of mercury | Standard Deviation 11.17 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 22 | -8.4 millimeter of mercury | Standard Deviation 17.55 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 25 | -5.8 millimeter of mercury | Standard Deviation 19.51 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | DBP: Baseline | 78.1 millimeter of mercury | Standard Deviation 10.91 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Lead in Phase: DBP: Change at Day 1 | -8.0 millimeter of mercury | Standard Deviation 11.31 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 1 | -2.2 millimeter of mercury | Standard Deviation 9.91 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 8 | -3.9 millimeter of mercury | Standard Deviation 10.99 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 22 | -5.0 millimeter of mercury | Standard Deviation 10.95 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 25 | -3.3 millimeter of mercury | Standard Deviation 11.44 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 39 | -5.1 millimeter of mercury | Standard Deviation 12.14 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: DBP: Change at Day 43 | -4.7 millimeter of mercury | Standard Deviation 11.76 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle1/Day 1 | -4.3 millimeter of mercury | Standard Deviation 11.67 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle1/Day 15 | -4.0 millimeter of mercury | Standard Deviation 10.96 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle2/Day 1 | -3.3 millimeter of mercury | Standard Deviation 12.31 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle3/Day 1 | -3.6 millimeter of mercury | Standard Deviation 11.42 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle3/Day 15 | -3.4 millimeter of mercury | Standard Deviation 11.1 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle4/Day 1 | -3.4 millimeter of mercury | Standard Deviation 11.42 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle4/Day 15 | -3.3 millimeter of mercury | Standard Deviation 11.54 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle5/Day 1 | -3.2 millimeter of mercury | Standard Deviation 10.88 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle5/Day 15 | -3.5 millimeter of mercury | Standard Deviation 10.69 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle6/Day 1 | -3.8 millimeter of mercury | Standard Deviation 11.28 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle6/Day 15 | -4.6 millimeter of mercury | Standard Deviation 11.43 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle7/Day 1 | -4.2 millimeter of mercury | Standard Deviation 11.52 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle7/Day 15 | -3.8 millimeter of mercury | Standard Deviation 10.88 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle8/Day 1 | -4.1 millimeter of mercury | Standard Deviation 10.95 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle8/Day 15 | -4.0 millimeter of mercury | Standard Deviation 12.29 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle9/Day 1 | -4.2 millimeter of mercury | Standard Deviation 10.98 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle9/Day 15 | -3.7 millimeter of mercury | Standard Deviation 12.07 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle10/Day 1 | -3.5 millimeter of mercury | Standard Deviation 11.54 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle10/Day 15 | -4.4 millimeter of mercury | Standard Deviation 11.69 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle11/Day 1 | -4.6 millimeter of mercury | Standard Deviation 11.23 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle11/Day 15 | -3.9 millimeter of mercury | Standard Deviation 10.22 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle12/Day 1 | -3.5 millimeter of mercury | Standard Deviation 11.4 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle12/Day 15 | -4.6 millimeter of mercury | Standard Deviation 11.19 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle13/Day 1 | -3.3 millimeter of mercury | Standard Deviation 11.49 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle13/Day 15 | -3.8 millimeter of mercury | Standard Deviation 11.44 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | SBP: Baseline | 130.5 millimeter of mercury | Standard Deviation 17.44 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Lead in Phase: SBP: Change at Day 1 | 12.5 millimeter of mercury | Standard Deviation 6.36 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 1 | -3.5 millimeter of mercury | Standard Deviation 14.82 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 8 | -8.0 millimeter of mercury | Standard Deviation 17.58 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 39 | -10.3 millimeter of mercury | Standard Deviation 19.05 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | CRT Phase: SBP: Change at Day 43 | -9.2 millimeter of mercury | Standard Deviation 19.52 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle1/Day 1 | -9.4 millimeter of mercury | Standard Deviation 20.19 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle1/Day 15 | -8.2 millimeter of mercury | Standard Deviation 19.58 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle2/Day 1 | -7.8 millimeter of mercury | Standard Deviation 20.09 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at /Cycle2/Day 15 | -6.6 millimeter of mercury | Standard Deviation 19.73 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle3/Day 1 | -8.5 millimeter of mercury | Standard Deviation 18.04 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle3/Day 15 | -7.1 millimeter of mercury | Standard Deviation 19.9 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle4/Day 1 | -8.9 millimeter of mercury | Standard Deviation 18.41 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle4/Day 15 | -8.2 millimeter of mercury | Standard Deviation 19.62 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Maintenance/Cycle5/Day 1 | -7.7 millimeter of mercury | Standard Deviation 18.69 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle5/Day 15 | -7.5 millimeter of mercury | Standard Deviation 18.49 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle6/Day 1 | -8.3 millimeter of mercury | Standard Deviation 18.96 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle6/Day 15 | -9.4 millimeter of mercury | Standard Deviation 19.56 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle7/Day 1 | -8.9 millimeter of mercury | Standard Deviation 18.96 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle7/Day 15 | -6.8 millimeter of mercury | Standard Deviation 18.73 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle8/Day 1 | -9.4 millimeter of mercury | Standard Deviation 18.65 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle8/Day 15 | -7.9 millimeter of mercury | Standard Deviation 18.21 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle9/Day 1 | -8.1 millimeter of mercury | Standard Deviation 18.41 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle9/Day 15 | -6.7 millimeter of mercury | Standard Deviation 20.28 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle10/Day 1 | -7.2 millimeter of mercury | Standard Deviation 18.63 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle10/Day 15 | -7.7 millimeter of mercury | Standard Deviation 18.76 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle11/Day 1 | -7.7 millimeter of mercury | Standard Deviation 18.86 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle11/Day 15 | -7.4 millimeter of mercury | Standard Deviation 18.65 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle12/Day 1 | -6.1 millimeter of mercury | Standard Deviation 20.21 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle12/Day 15 | -7.8 millimeter of mercury | Standard Deviation 19.12 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle13/Day 1 | -6.2 millimeter of mercury | Standard Deviation 18.54 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: SBP: Change at Cycle13/Day 15 | -5.6 millimeter of mercury | Standard Deviation 19 |
| Placebo + SOC CRT | Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure | Maintenance Phase: DBP: Change at Cycle2/Day 15 | -2.3 millimeter of mercury | Standard Deviation 11.82 |
Secondary
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin
Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). AUClast (dn) was calculated by dividing AUClast by the exact dose of cisplastin (in mg) administered to a participant.
Time frame: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Population: PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin | Total Cisplatin | 299.1 nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 30 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin | Free Cisplatin | 36.53 nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 51 |
| Placebo + SOC CRT | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin | Free Cisplatin | 29.08 nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 49 |
| Placebo + SOC CRT | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin | Total Cisplatin | 332.7 nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 17 |
Secondary
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin
Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of total and free Cisplastin (in mg) administered to a participant.
Time frame: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Population: PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin | Total Cisplastin | 26.23 nanogram per milliliter per milligram | Geometric Coefficient of Variation 36 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin | Free Cisplastin | 11.84 nanogram per milliliter per milligram | Geometric Coefficient of Variation 29 |
| Placebo + SOC CRT | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin | Free Cisplastin | 7.286 nanogram per milliliter per milligram | Geometric Coefficient of Variation 96 |
| Placebo + SOC CRT | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin | Total Cisplastin | 25.33 nanogram per milliliter per milligram | Geometric Coefficient of Variation 26 |
Secondary
Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator
DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:\>=30% decrease under baseline of sum of diameters of all target measurable lesions. CR for target disease:complete disappearance of all target lesions with exception of nodal disease.CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. PD is any of following:1)Locoregional PD confirmed by pathology to verify radiographic changes denote true tumor progression and not radiation effects or non-malignant contrast enhancement.2)Locoregional clinically detectable progression confirmed by pathology.3)Surgical removal of primary tumor with tumor present on final pathology.4)Salvage neck dissection \>20 weeks after completion of CRT with tumor present on final pathology.5)Metastatic PD. DOR data was censored on date of last adequate tumor assessment for participants with no overall response.
Time frame: From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months)
Population: Analysis population included all randomized participants who had unconfirmed CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator | NA months |
| Placebo + SOC CRT | Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator | NA months |
Secondary
Maximum Plasma Concentration (Cmax) of Avelumab
Maximum observed plasma concentration (Cmax) of Avelumab is reported.
Time frame: Pre-dose and end of infusion on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1 and 2 (each cycle 28 days)
Population: PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'number analyzed' signifies participants evaluable at specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Avelumab | Lead-in/Day 1 | 203.6 microgram per milliliter | Geometric Coefficient of Variation 31 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Avelumab | CRT/Day 8 | 190.9 microgram per milliliter | Geometric Coefficient of Variation 66 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Avelumab | CRT/Day 25 | 162.4 microgram per milliliter | Geometric Coefficient of Variation 114 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Avelumab | Cycle 1 Day 1 | 142 microgram per milliliter | Geometric Coefficient of Variation 117 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Avelumab | Cycle 2 Day 1 | 154.9 microgram per milliliter | Geometric Coefficient of Variation 97 |
Secondary
Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin
Maximum observed plasma concentration (Cmax) of total and free Cisplatin is reported.
Time frame: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Population: PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin | Total Cisplatin | 3781 nanogram per milliliter | Geometric Coefficient of Variation 44 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin | Free Cisplatin | 1710 nanogram per milliliter | Geometric Coefficient of Variation 53 |
| Placebo + SOC CRT | Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin | Total Cisplatin | 4001 nanogram per milliliter | Geometric Coefficient of Variation 34 |
| Placebo + SOC CRT | Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin | Free Cisplatin | 1151 nanogram per milliliter | Geometric Coefficient of Variation 109 |
Secondary
Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells
Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm\^2).
Time frame: Baseline (prior to first dose)
Population: Biomarker analysis set included all participants who had received at least one dose of study drug and who had at least one screening biomarker assessment. Here, 'Overall number of participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells | 4.9 % of tumor area occupied by CD8+ cells | Standard Deviation 6.03 |
| Placebo + SOC CRT | Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells | 5.8 % of tumor area occupied by CD8+ cells | Standard Deviation 6.55 |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
ADA never-positive was defined as no positive ADA results at any time point; ADA-negative participants (titer less than\< cut point) and ADA ever-positive was defined as at least one positive ADA result at any time point; ADA-positive participants (titer greater than or equal to cut point)
Time frame: pre-dose on Day 1 up to 30 Days after the end of treatment
Population: Immunogenicity analysis set was a subset of the safety analysis set which included participants who had at least 1 ADA/nAb sample collected for avelumab in Avelumab + Standard of Care Chemotherapy (SOC CRT) arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status | ADA never-positive | 277 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status | ADA ever-positive | 54 Participants |
Secondary
Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status
Time frame: Day 1 of lead-in phase and on Days 8 and 25 of CRT phase
Population: Since the study was terminated, sponsor decided not to collect data for nAb, hence not reported.
Secondary
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters
Grade 1 and 3 ranges are: Anemia:Hb:\<LLN-10.0,\<8.0 g/dL;LC decreased (dec):\<LLN-800/mm\^3,500-200/mm\^3;LC increased (inc):grade 3:\>20,000/mm\^3:NC dec:\<LLN-1500/mm\^3;\<1000-500/mm\^3;PC dec:\<LLN-75,000/mm\^3;\<50,000-25,000/mm\^3;WBC dec:\<LLN-3000/mm\^3;\<2000-1000/mm\^3;ALT inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;ALP & GGT inc:\>ULN-2.5\*ULN;\>5.0-20.0\*ULN;AST inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;BB inc:\>ULN-1.5\*ULN;\>3.0-10.0\*ULN;CH high:\>ULN-300 mg/dL;\>400-500 mg/dL;CPK inc:\>ULN-2.5\*ULN;\>5\*ULN-10\*ULN;Hypercalcemia:\>ULN-11.5;\>12.5-13.5mg/dL;Hyperglycemia:\>ULN-160; \>250-500mg/dL;Hyperkalemia:\>ULN-5.5;\>6.0-7.0mmol/L;Hypermagnesemia:\>ULN-3.0;\>3.0-8.0 mg/dL;Hypernatremia:\>ULN-150; \>155-160 mmol/L;Hypertriglyceridemia;150-300;\>500-1000 mg/dL;Hypoalbuminemia:\<LLN-3;\<2g/dL;Hypocalcemia:\<LLN-8.0;\<8.0-7.0mg/dL;Hypokalemia:\<LLN-3.0;\<3.0-2.5mmol/L;Hypomagnesemia;\<LLN-1.2;\<0.9-0.7 mg/dL;Hyponatremia:\<LLN-130;\<130-120mmol/L; Hypophosphatemia:\<LLN-2.5;\<2.0-1.0mg/dL;lipase & serum amylase inc:\>ULN-1.5\*ULN;\>2.0-5.0\*ULN.
Time frame: Baseline up to 15 months
Population: Safety population include all participants who received at least one dose of study drug. Here Overall Number of Participants analyzed signifies number of participants evaluable for this outcome measure and 'Number analyzed' signifies number of participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | White Blood Cell (WBC) Decreased: New or worsened to grade >=1 | 309 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypercalcemia: New or worsened to grade >=1 | 67 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | White Blood Cell Decreased: New or worsened to grade >=3 | 121 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypercalcemia: New or worsened to grade >=3 | 1 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Platelet Count Decreased: New or worsened to grade >=3 | 20 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperglycemia: New or worsened to grade >=1 | 144 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperglycemia: New or worsened to grade >=3 | 28 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Alanine aminotransferase (ALT) increased: New or worsened to grade >=1 | 152 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperkalemia: New or worsened to grade >=1 | 106 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Anemia: New or worsened to grade >=3 | 42 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperkalemia: New or worsened to grade >=3 | 9 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypermagnesemia: New or worsened to grade >=1 | 39 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Aspartate aminotransferase (AST) increased: New or worsened to grade >=1 | 146 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypermagnesemia: New or worsened to grade >=3 | 10 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Alkaline phosphatase increased (ALP): New or worsened to grade >=1 | 72 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypernatremia: New or worsened to grade >=1 | 22 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count Decreased: New or worsened to grade >=1 | 336 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypernatremia: New or worsened to grade >=3 | 1 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Blood bilirubin (BB) increased (BB): New or worsened to grade >=1 | 58 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypertriglyceridemia: New or worsened to grade >=1 | 35 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Aspartate aminotransferase increased: New or worsened to grade >=3 | 11 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypertriglyceridemia: New or worsened to grade >=3 | 1 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count (LC) Decreased: New or worsened to grade >=3 | 279 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoalbuminemia: New or worsened to grade >=1 | 195 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Blood bilirubin increased: New or worsened to grade >=3 | 9 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoalbuminemia: New or worsened to grade >=3 | 7 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count (LC) Increased: New or worsened to grade >=1 | 7 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypocalcemia: New or worsened to grade >=1 | 82 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Cholesterol (CH) high: New or worsened to grade >=1 | 25 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypocalcemia: New or worsened to grade >=3 | 8 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | ALT increased: New or worsened to grade >=3 | 13 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoglycemia: New or worsened to grade >=1 | 56 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Cholesterol high: New or worsened to grade >=3 | 0 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoglycemia: New or worsened to grade >=3 | 2 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count Increased: New or worsened to grade >=3 | 0 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypokalemia: New or worsened to grade >=1 | 140 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | CPK increased: New or worsened to grade >=1 | 7 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypokalemia: New or worsened to grade >=3 | 55 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Alkaline phosphatase increased: New or worsened to grade >=3 | 1 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypomagnesemia: New or worsened to grade >=1 | 180 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | CPK increased: New or worsened to grade >=3 | 0 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypomagnesemia: New or worsened to grade >=3 | 8 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyponatremia: New or worsened to grade >=1 | 232 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Creatinine increased: New or worsened to grade >=1 | 334 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyponatremia: New or worsened to grade >=3 | 74 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Neutrophil Count Decreased: New or worsened to grade >=3 | 120 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypophosphatemia: New or worsened to grade >=1 | 108 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Creatinine increased: New or worsened to grade >=3 | 36 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypophosphatemia: New or worsened to grade >=3 | 21 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Anemia: New or worsened to grade >=1 | 314 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lipase increased: New or worsened to grade >=1 | 19 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | GGT increased: New or worsened to grade >=1 | 37 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lipase increased: New or worsened to grade >=3 | 11 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Platelet Count (PC) Decreased : New or worsened to grade >=1 | 157 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Serum amylase increased: New or worsened to grade >=1 | 13 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | GGT increased: New or worsened to grade >=3 | 10 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Serum amylase increased: New or worsened to grade >=3 | 9 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Neutrophil Count (NC) Decreased: New or worsened to grade >=1 | 257 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Serum amylase increased: New or worsened to grade >=3 | 5 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Platelet Count (PC) Decreased : New or worsened to grade >=1 | 154 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Platelet Count Decreased: New or worsened to grade >=3 | 7 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | White Blood Cell (WBC) Decreased: New or worsened to grade >=1 | 307 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Alkaline phosphatase increased: New or worsened to grade >=3 | 1 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperkalemia: New or worsened to grade >=3 | 17 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperglycemia: New or worsened to grade >=1 | 137 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Anemia: New or worsened to grade >=1 | 311 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Anemia: New or worsened to grade >=3 | 49 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count Decreased: New or worsened to grade >=1 | 330 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count (LC) Decreased: New or worsened to grade >=3 | 284 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count (LC) Increased: New or worsened to grade >=1 | 7 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lymphocyte Count Increased: New or worsened to grade >=3 | 0 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Neutrophil Count (NC) Decreased: New or worsened to grade >=1 | 237 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Neutrophil Count Decreased: New or worsened to grade >=3 | 101 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | White Blood Cell Decreased: New or worsened to grade >=3 | 129 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Alanine aminotransferase (ALT) increased: New or worsened to grade >=1 | 135 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | ALT increased: New or worsened to grade >=3 | 2 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Alkaline phosphatase increased (ALP): New or worsened to grade >=1 | 49 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Aspartate aminotransferase (AST) increased: New or worsened to grade >=1 | 111 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Aspartate aminotransferase increased: New or worsened to grade >=3 | 4 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Blood bilirubin (BB) increased (BB): New or worsened to grade >=1 | 54 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Blood bilirubin increased: New or worsened to grade >=3 | 4 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Cholesterol (CH) high: New or worsened to grade >=1 | 21 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Cholesterol high: New or worsened to grade >=3 | 0 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | CPK increased: New or worsened to grade >=1 | 7 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | CPK increased: New or worsened to grade >=3 | 1 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Creatinine increased: New or worsened to grade >=1 | 325 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Creatinine increased: New or worsened to grade >=3 | 37 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | GGT increased: New or worsened to grade >=1 | 23 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | GGT increased: New or worsened to grade >=3 | 5 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypercalcemia: New or worsened to grade >=1 | 59 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypercalcemia: New or worsened to grade >=3 | 5 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperglycemia: New or worsened to grade >=3 | 29 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyperkalemia: New or worsened to grade >=1 | 113 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypermagnesemia: New or worsened to grade >=1 | 40 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypermagnesemia: New or worsened to grade >=3 | 10 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypernatremia: New or worsened to grade >=1 | 20 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypernatremia: New or worsened to grade >=3 | 0 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypertriglyceridemia: New or worsened to grade >=1 | 26 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypertriglyceridemia: New or worsened to grade >=3 | 2 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoalbuminemia: New or worsened to grade >=1 | 170 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoalbuminemia: New or worsened to grade >=3 | 5 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypocalcemia: New or worsened to grade >=1 | 88 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypocalcemia: New or worsened to grade >=3 | 14 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoglycemia: New or worsened to grade >=1 | 44 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypoglycemia: New or worsened to grade >=3 | 2 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypokalemia: New or worsened to grade >=1 | 122 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypokalemia: New or worsened to grade >=3 | 49 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypomagnesemia: New or worsened to grade >=1 | 158 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypomagnesemia: New or worsened to grade >=3 | 12 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyponatremia: New or worsened to grade >=1 | 212 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hyponatremia: New or worsened to grade >=3 | 70 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypophosphatemia: New or worsened to grade >=1 | 100 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Hypophosphatemia: New or worsened to grade >=3 | 19 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lipase increased: New or worsened to grade >=1 | 13 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Lipase increased: New or worsened to grade >=3 | 3 Participants |
| Placebo + SOC CRT | Number of Participants With Shift From Baseline in Clinical Laboratory Parameters | Serum amylase increased: New or worsened to grade >=1 | 10 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period.
Time frame: Baseline up to 44 months
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 2 | 30 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 4 | 59 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 3 | 224 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 5 | 22 Participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 1 | 10 Participants |
| Placebo + SOC CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 5 | 17 Participants |
| Placebo + SOC CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 1 | 8 Participants |
| Placebo + SOC CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 2 | 53 Participants |
| Placebo + SOC CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 3 | 215 Participants |
| Placebo + SOC CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Grade 4 | 49 Participants |
Secondary
Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator
Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than \[\<\] 10 millimeter \[mm\]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (\<10 mm short axis) . PR: Greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized.
Time frame: From randomization until disease progression or death, whichever occurred first (up to 37 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator | 74.0 percentage of participants |
| Placebo + SOC CRT | Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator | 74.9 percentage of participants |
p-value: 0.622995% CI: [0.663, 1.352]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method.
Time frame: From randomization to the date of death or censored date, whichever occurred first (up to 37 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Overall Survival (OS) | NA months |
| Placebo + SOC CRT | Overall Survival (OS) | NA months |
p-value: 0.937295% CI: [0.927, 1.849]Log Rank
Secondary
Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site
pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site.
Time frame: From randomization until PD or death (up to 37 months)
Population: All randomized participants who had salvage surgery at the primary site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site | 0 percentage of participants |
| Placebo + SOC CRT | Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site | 14.3 percentage of participants |
Secondary
Percentage of Participants With Positive and Negative Pathology of Neck Dissection
Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study.
Time frame: From randomization until PD as per investigator assessment (up to 37 months)
Population: Analysis population included all participants who had received at least one dose of study drug and who had salvage neck dissection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Percentage of Participants With Positive and Negative Pathology of Neck Dissection | Positive pathology | 71.43 percentage of participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Percentage of Participants With Positive and Negative Pathology of Neck Dissection | Pathology not reported | 21.43 percentage of participants |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Percentage of Participants With Positive and Negative Pathology of Neck Dissection | Negative Pathology | 7.14 percentage of participants |
| Placebo + SOC CRT | Percentage of Participants With Positive and Negative Pathology of Neck Dissection | Negative Pathology | 26.70 percentage of participants |
| Placebo + SOC CRT | Percentage of Participants With Positive and Negative Pathology of Neck Dissection | Positive pathology | 40.00 percentage of participants |
| Placebo + SOC CRT | Percentage of Participants With Positive and Negative Pathology of Neck Dissection | Pathology not reported | 33.30 percentage of participants |
Secondary
Predose Plasma Concentration (Ctrough) of Avelumab
Ctrough refers to plasma concentration of Avelumab observed just before treatment administration.
Time frame: Pre-dose on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1, 2, 5, 8, 11 (each cycle 28 days)
Population: PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'number analyzed' signifies participants evaluable at specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | Lead-in/Day 1 | 2.988 microgram per milliliter | Geometric Coefficient of Variation 1590 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | CRT/Day 8 | 11.9 microgram per milliliter | Geometric Coefficient of Variation 63 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | CRT/Day 25 | 6.284 microgram per milliliter | Geometric Coefficient of Variation 138 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | Cycle 1/Day 1 | 2.354 microgram per milliliter | Geometric Coefficient of Variation 131 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | Cycle 2/Day 1 | 17.56 microgram per milliliter | Geometric Coefficient of Variation 70 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | Cycle 5/Day 1 | 24.35 microgram per milliliter | Geometric Coefficient of Variation 66 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | Cycle 8/Day 1 | 29.59 microgram per milliliter | Geometric Coefficient of Variation 69 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Predose Plasma Concentration (Ctrough) of Avelumab | Cycle 11/Day 1 | 30.85 microgram per milliliter | Geometric Coefficient of Variation 79 |
Secondary
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells.
Time frame: Baseline (prior to first dose)
Population: Biomarker analysis set was a subset of the safety analysis set included participants who had at least one screening biomarker assessment. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) | Positive Immune Cells | 7.4 % of PD-L1+ cells | Standard Deviation 7.06 |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) | Tumor Staining Cells | 12.7 % of PD-L1+ cells | Standard Deviation 24.9 |
| Placebo + SOC CRT | Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) | Tumor Staining Cells | 18.3 % of PD-L1+ cells | Standard Deviation 31.12 |
| Placebo + SOC CRT | Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) | Positive Immune Cells | 8.3 % of PD-L1+ cells | Standard Deviation 8.47 |
Secondary
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin
Time to reach maximum observed plasma concentration (Tmax) of total and free Cisplatin.
Time frame: Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase
Population: PK concentration analysis was a subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab or cisplatin. Here' 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin | Total Cisplatin | 1.000 hour |
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin | Free Cisplatin | 1.000 hour |
| Placebo + SOC CRT | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin | Total Cisplatin | 1.170 hour |
| Placebo + SOC CRT | Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin | Free Cisplatin | 1.000 hour |
Secondary
Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator
Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method.
Time frame: From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator | NA months |
| Placebo + SOC CRT | Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator | NA months |
p-value: 0.906195% CI: [0.909, 1.624]Log Rank
Secondary
Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator
Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method.
Time frame: From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months)
Population: FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab + Standard of Care Chemotherapy (SOC CRT) | Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator | NA months |
| Placebo + SOC CRT | Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator | NA months |
p-value: 0.931695% CI: [0.93, 1.694]Log Rank