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Avelumab in Participants With Merkel Cell Carcinoma (JAVELIN Merkel 200)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02155647
Recruitment Status : Active, not recruiting
First Posted : June 4, 2014
Results First Posted : July 22, 2020
Last Update Posted : July 22, 2020
Sponsor:
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Merkel Cell
Intervention Drug: Avelumab
Enrollment 204
Recruitment Details First participant enrolled 03 July 2014. Clinical data cut-off: 03 March 2016 (Part A) and 02 May 2019 (Part B).
Pre-assignment Details A total of 88 participants were enrolled in Part A of the study and a total of 116 participants were enrolled in Part B of the study. Participants enrolled in Part A were not eligible for enrollment in Part B.
Arm/Group Title Part A: Avelumab Part B: Avelumab
Hide Arm/Group Description Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs. Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Period Title: Overall Study
Started 88 116
Completed 47 64
Not Completed 41 52
Reason Not Completed
Still on Treatment             26             26
Off-Treatment, but follow up ongoing             15             26
Arm/Group Title Part A: Avelumab Part B: Avelumab Total
Hide Arm/Group Description Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs. Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs. Total of all reporting groups
Overall Number of Baseline Participants 88 116 204
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 116 participants 204 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
22
  25.0%
22
  19.0%
44
  21.6%
>=65 years
66
  75.0%
94
  81.0%
160
  78.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 116 participants 204 participants
Female
23
  26.1%
35
  30.2%
58
  28.4%
Male
65
  73.9%
81
  69.8%
146
  71.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 116 participants 204 participants
Hispanic or Latino
4
   4.5%
29
  25.0%
33
  16.2%
Not Hispanic or Latino
58
  65.9%
75
  64.7%
133
  65.2%
Unknown or Not Reported
26
  29.5%
12
  10.3%
38
  18.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 116 participants 204 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   3.4%
3
   2.6%
6
   2.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
   1.7%
2
   1.0%
White
81
  92.0%
75
  64.7%
156
  76.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   4.5%
36
  31.0%
40
  19.6%
1.Primary Outcome
Title Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Hide Description Confirmed BOR was determined according to RECIST 1.1and as adjudicated by an Independent Endpoint Review Committee(IERC) and defined as best response of any of complete response (CR), partial response(PR), stable disease(SD) and progressive disease(PD) recorded from date of randomization until disease progression/recurrence(taking smallest measurement recorded since start of treatment as reference). CR:Disappearance of all evidence of target/non-target lesions. PR:At least 30%reduction from baseline in sum of longest diameter(SLD) of all lesions. SD:Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD:at least a20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. CR or PR must be confirmed by a subsequent tumor assessment preferably at next scheduled 6-weekly assessment, but no sooner than 5 weeks after initial documentation of CR or PR.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
8
   9.1%
Partial Response
20
  22.7%
Stable Disease
9
  10.2%
Non-complete Response/ Non-progressive Disease
1
   1.1%
Progressive Disease
32
  36.4%
Not evaluable
18
  20.5%
2.Primary Outcome
Title Part B: Durable Response Rate (DRR)
Hide Description Durable response is defined as an objective response (confirmed complete response [CR] or confirmed Partial response [PR]) according to Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1, determined by the Independent Endpoint Review Committee (IERC), with a duration of at least 6 months. The DRR was determined as the percentage of participants with an objective response in terms of CR or PR according to RECIST 1.1, as determined by the IERC, with a duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time Frame Up to 161 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
30.2
(22.0 to 39.4)
3.Secondary Outcome
Title Part A: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Hide Description The duration of response as determined from IERC tumor assessment was calculated for each participant with a confirmed response (CR or PR) as the time from first observation of response until first observation of documented disease progression or death when death occurs within 12 weeks of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Results were calculated based on Kaplan-Meier estimates.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(8.3 to NA)
[1]
Due to small number of events, estimates (Median and upper limit) from Kaplan-Meier survival curves could not derive.
4.Secondary Outcome
Title Part A: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Hide Description The PFS time (based on IERC tumor assessments), according to the RECIST 1.1, was defined as the time from first administration of study treatment until first observation of PD or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). PFS time (in months) was defined as: (date of PD or death - date of the first dose of study treatment + 1)/30.4375 (months). PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Median (Full Range)
Unit of Measure: Months
2.7
(0.03 to 18.8)
5.Secondary Outcome
Title Part A: Number of Participants With Treatment-Related (TR) Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Serious TEAEs and Treatment-Related TEAEs Leading to Death
Hide Description Related Adverse events (AE) were defined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE) as adverse events with relationship to study treatment reported by the investigator. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. Related TEAEs are defined as events with a relationship of missing, unknown, or yes.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with TR-TEAEs
62
  70.5%
Participants with TR-Serious-TEAEs
5
   5.7%
Participants with TR-TEAEs leading to Death
0
   0.0%
6.Secondary Outcome
Title Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description The laboratory measurements included hematology, liver function and blood chemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (>=) 3 in laboratory values reported as TEAEs were reported. Clinically Significance was decided by investigator.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia
9
  10.2%
Lymphocyte count decreased
18
  20.5%
Neutrophil count decreased
1
   1.1%
Platelet count decreased
1
   1.1%
White blood cell count decreased
1
   1.1%
Hypoalbuminemia
2
   2.3%
Alkaline phosphatase increased
1
   1.1%
Alanine aminotransferase increased
3
   3.4%
Serum amylase increased
1
   1.1%
Aspartate aminotransferase increased
1
   1.1%
Blood bilirubin increased
1
   1.1%
Cholesterol high
1
   1.1%
Creatine phosphokinase increased
1
   1.1%
Creatinine increased
2
   2.3%
Chronic kidney disease
3
   3.4%
Gamma-glutamyltransferase increased
6
   6.8%
Hyperglycemia
7
   8.0%
Hypoglycemia
1
   1.1%
Hyperkalemia
1
   1.1%
Hypokalemia
2
   2.3%
Lipase increased
4
   4.5%
Hypermagnesemia
1
   1.1%
Hypophosphatemia
3
   3.4%
Hyponatremia
11
  12.5%
Hypertriglyceridemia
1
   1.1%
7.Secondary Outcome
Title Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description Vital signs including body temperature, body weight, respiratory rate, heart rate (after 5-minute rest), and arterial blood pressure (after 5-minute rest) were evaluated. Number of participants with clinically significant abnormalities in Vital Signs reported as TEAEs. Clinically Significance was decided by investigator.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Measure Type: Count of Participants
Unit of Measure: Participants
Body temperature Increased
0
   0.0%
Weight Increased
57
  64.8%
Weight Decreased
54
  61.4%
Increased Heart Rate
83
  94.3%
Decreased Heart Rate
84
  95.5%
Increased Systolic Blood Pressure
84
  95.5%
Decreased Systolic Blood Pressure
84
  95.5%
Increased Diastolic Blood Pressure
84
  95.5%
Decreased Diastolic Blood Pressure
84
  95.5%
Increased Respiratory Rate
81
  92.0%
Decreased Respiratory Rate
81
  92.0%
8.Secondary Outcome
Title Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
Hide Description A 12-lead ECG was recorded after the participant has been in a supine position breathing quietly for 5 minutes. The ECG results was used to evaluate the heart rate, atrial ventricular conduction, PR interval, QRS, QTcF and QTcB. Number of participants with clinical significant abnormalities in ECG parameter reported here. Clinically Significance was decided by investigator.
Time Frame Up to 87 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment. Here "Number of participants analyzed" signifies those who were evaluable for this outcome measure.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 81
Measure Type: Count of Participants
Unit of Measure: Participants
PR interval >= 220 ms
16
  19.8%
QRS >= 120 ms
12
  14.8%
QTcF > 30 ms and <= 60 ms
20
  24.7%
QTcF > 60 ms
1
   1.2%
QTcB > 30 ms and <= 60 ms
25
  30.9%
QTcB > 60 ms
2
   2.5%
Heart rate <= 50 bpm
3
   3.7%
Heart rate >= 120 bpm
2
   2.5%
9.Secondary Outcome
Title Part A: Interim Analysis: Overall Survival (OS) Time
Hide Description The OS time was defined as the time from first administration of trial treatment until death. The OS time was analyzed using the Kaplan-Meier method.
Time Frame Up to 87 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 3 Mar 2016)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Median (95% Confidence Interval)
Unit of Measure: Months
11.3
(7.5 to 14.0)
10.Secondary Outcome
Title Part A: Final Analysis: Overall Survival (OS) Time
Hide Description The OS time was defined as the time from first administration of trial treatment until death. The OS time was analyzed using the Kaplan-Meier method.
Time Frame Pre-specified final analysis: Time from first administration of trial treatment until death (Up to 513 weeks)
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months
Hide Description The response status at 6 and 12 months after start of trial treatment according to RECIST 1.1 (as determined by the IERC) was determined. A participant was considered to be in response at the given timepoint (6 or 12 months after the start of the participant's treatment) if the participant had a documented response (PR or CR) prior to that timepoint, and neither died nor experienced disease progression according to the RECIST 1.1 nor was lost to follow-up up to the given timepoint. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Percentage of participants in response and not in response according to RECIST1.1 at 6 and 12 months were reported.
Time Frame At Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Measure Type: Number
Unit of Measure: Percentage of participants
In-response at Month 6 30.7
In-response at Month 12 20.7
Not in-response at Month 6 69.3
Not In-response at Month 12 79.3
12.Secondary Outcome
Title Part A: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies
Hide Description Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of anti-avelumab antibodies. Samples that screened positive were subsequently tested in a confirmatory assay. Those confirmed positive were titered for a quasi-quantitative result. Number of participants with positive treatment emergent anti-Avelumab antibodies were reported. Participants not positive prior to treatment with avelumab and with at least one positive result in the human-Antihuman Antibodies assay were characterized as treatment-emergent.
Time Frame Up to 80 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment. Here "Number of participants analyzed" signifies those who were evaluable for this outcome measure.
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 82
Measure Type: Count of Participants
Unit of Measure: Participants
3
   3.7%
13.Secondary Outcome
Title Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab
Hide Description Serum concentration at end of infusion (CEOI) of Avelumab is reported.
Time Frame Day 1, 43, 85, 169, 253, 337 and 421
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set consists of all participants who received at least 1 dose of avelumab, and provide at least 1 measurable post-dose concentration. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Mean (Standard Deviation)
Unit of Measure: Micrograms per milliliter
Day 1 Number Analyzed 59 participants
252  (129)
Day 43 Number Analyzed 48 participants
266  (74.2)
Day 85 Number Analyzed 30 participants
274  (57.7)
Day 169 Number Analyzed 23 participants
315  (65.0)
Day 253 Number Analyzed 15 participants
318  (70.1)
Day 337 Number Analyzed 6 participants
373  (48.3)
Day 421 Number Analyzed 4 participants
453  (71.5)
14.Secondary Outcome
Title Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb
Hide Description Minimum serum post-dose (Ctrough) concentration of avelumab was reported.
Time Frame Day 15, 29, 43, 57, 71, 85, 99, 169, 211, 253, 337 and 421
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set consists of all participants who received at least 1 dose of avelumab, and provide at least 1 measurable post-dose concentration. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints
Arm/Group Title Part A: Avelumab
Hide Arm/Group Description:
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 88
Mean (Standard Deviation)
Unit of Measure: Micrograms per milliliter
Day 15 Number Analyzed 77 participants
23.8  (28.4)
Day 29 Number Analyzed 69 participants
26.4  (13.7)
Day 43 Number Analyzed 69 participants
32.3  (35.8)
Day 57 Number Analyzed 56 participants
32.7  (18.8)
Day 71 Number Analyzed 52 participants
33.5  (21.1)
Day 85 Number Analyzed 42 participants
45.5  (53.6)
Day 99 Number Analyzed 37 participants
40.3  (24.0)
Day 169 Number Analyzed 24 participants
43.6  (19.6)
Day 211 Number Analyzed 1 participants
57.2
Day 253 Number Analyzed 11 participants
38.4  (15.7)
Day 337 Number Analyzed 4 participants
43.9  (23.7)
Day 421 Number Analyzed 2 participants
61.4  (7.79)
15.Secondary Outcome
Title Part B: Interim Analysis: Overall Survival (OS) Time
Hide Description The OS time was defined as the time from first administration of study treatment until the date of death. OS was calculated using following formula = (date of death - date of the first dose of study treatment + 1)/30.4375 (months).
Time Frame Up to 161 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 2 May 2019)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Median (Full Range)
Unit of Measure: Months
20.3
(0.5 to 34.9)
16.Secondary Outcome
Title Part B: Final Analysis: Overall Survival (OS) Time
Hide Description The OS time was defined as the time from first administration of study treatment until the date of death. OS was calculated using following formula = (date of death - date of the first dose of study treatment + 1)/30.4375 (months).
Time Frame Pre-specified final analysis: Time from first administration of trial treatment until death (Up to 422 weeks)
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Hide Description Confirmed BOR was determined according to RECIST 1.1and as adjudicated by an Independent Endpoint Review Committee(IERC) and defined as best response of any of complete response (CR), partial response(PR), stable disease(SD) and progressive disease(PD) recorded from date of randomization until disease progression/recurrence(taking smallest measurement recorded since start of treatment as reference). CR:Disappearance of all evidence of target/non-target lesions. PR:At least 30%reduction from baseline in sum of longest diameter(SLD) of all lesions. SD:Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD:at least a20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. CR or PR must be confirmed by a subsequent tumor assessment preferably at next scheduled 6-weekly assessment, but no sooner than 5 weeks after initial documentation of CR or PR.
Time Frame Up to 161 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
19
  16.4%
Partial Response
27
  23.3%
Stable Disease
12
  10.3%
Non-complete Response/ Non-progressive Disease
1
   0.9%
Progressive Disease
48
  41.4%
Not evaluable
9
   7.8%
18.Secondary Outcome
Title Part B: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Hide Description The duration of response as determined from IERC tumor assessment was calculated for each participant with a confirmed response (CR or PR) as the time from first observation of response until first observation of documented disease progression or death when death occurs within 12 weeks of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time Frame Up to 161 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 46
Median (Full Range)
Unit of Measure: Months
18.2
(1.2 to 28.3)
19.Secondary Outcome
Title Part B: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Hide Description The PFS time (based on IERC tumor assessments), according to the RECIST 1.1, was defined as the time from first administration of study treatment until first observation of PD or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). PFS time (in months) was defined as: (date of PD or death - date of the first dose of study treatment + 1)/30.4375 (months). PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions.
Time Frame Up to 161 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Median (Full Range)
Unit of Measure: Months
4.1
(0.03 to 29.6)
20.Secondary Outcome
Title Part B: Number of Participants With Treatment-Related (TR) Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Serious TEAEs and Treatment-Related TEAEs Leading to Death
Hide Description Related Adverse events (AE) were defined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE) as adverse events with relationship to study treatment reported by the investigator. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. Related TEAEs are defined as events with a relationship of missing, unknown, or yes.
Time Frame Up to 161 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with TR-TEAEs
94
  81.0%
Participants with TR-Serious-TEAEs
17
  14.7%
Participants with TR-TEAEs leading to Death
0
   0.0%
21.Secondary Outcome
Title Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months
Hide Description The response status at 6 and 12 months after start of trial treatment according to RECIST 1.1 (as determined by the IERC) was determined. A participant was considered to be in response at the given timepoint (6 or 12 months after the start of the participant's treatment) if the participant had a documented response (PR or CR) prior to that timepoint, and neither died nor experienced disease progression according to the RECIST 1.1 nor was lost to follow-up up to the given timepoint. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Percentage of participants in response and not in response according to RECIST1.1 at 6 and 12 months were reported.
Time Frame At Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Measure Type: Number
Unit of Measure: Percentage of Participants
In-response at Month 6 33.6
In-response at Month 12 26.7
Not in-response at Month 6 66.4
Not in-response at Month 12 73.3
22.Secondary Outcome
Title Part B: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies
Hide Description Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay. Those that confirmed positive were titered for a quasi-quantitative result. Number of participants with positive treatment emergent anti-Avelumab antibodies were reported. Participants not positive prior to treatment with avelumab and with at least one positive result in the human-Antihuman Antibodies assay were characterized as treatment-emergent.
Time Frame Up to 161 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who received at least 1 dose of study treatment. Here "Number of Participants analyzed" signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 110
Measure Type: Count of Participants
Unit of Measure: Participants
8
   7.3%
23.Secondary Outcome
Title Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab
Hide Description Serum concentration at end of infusion (CEOI) of Avelumab is reported.
Time Frame At Day 1, 43 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set included all participants who received at least 1 dose of avelumab, and provided at least 1 measurable post-dose concentration. Here "Number analyzed" signifies those participants who were evaluable at specified time-point for this outcome measure.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
Day 1 Number Analyzed 104 participants
237
(31.1%)
Day 43 Number Analyzed 78 participants
244
(32.1%)
Day 169 Number Analyzed 41 participants
255
(27.7%)
24.Secondary Outcome
Title Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb
Hide Description Minimum serum post-dose (Ctrough) concentration of avelumab was reported.
Time Frame Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505, Day 589, Day 673
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set included all participants who received at least 1 dose of avelumab, and provided at least 1 measurable post-dose concentration. Here "Number analyzed" signifies those participants who were evaluable at specified time-point for this outcome measure.
Arm/Group Title Part B: Avelumab
Hide Arm/Group Description:
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Overall Number of Participants Analyzed 116
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
Day 15 Number Analyzed 100 participants
22.2
(57.5%)
Day 29 Number Analyzed 86 participants
27.8
(80.2%)
Day 43 Number Analyzed 76 participants
27.5
(89.4%)
Day 85 Number Analyzed 61 participants
29.4
(130.4%)
Day 127 Number Analyzed 54 participants
37.0
(65.6%)
Day 169 Number Analyzed 45 participants
45.6
(60.3%)
Day 253 Number Analyzed 47 participants
39.9
(53.0%)
Day 337 Number Analyzed 36 participants
39.5
(37.3%)
Day 421 Number Analyzed 24 participants
43.6
(30.3%)
Day 505 Number Analyzed 14 participants
41.8
(30.4%)
Day 589 Number Analyzed 4 participants
57.5
(24.1%)
Day 673 Number Analyzed 5 participants
44.9
(21.4%)
Time Frame Part A: Up to 87 weeks; Part B: Up to 161 weeks
Adverse Event Reporting Description Adverse events were reported as per MedDRA v18.1 for Part A arm and MedDRA v22.0 for Part B.
 
Arm/Group Title Part A: Avelumab Part B: Avelumab
Hide Arm/Group Description Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs. Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
All-Cause Mortality
Part A: Avelumab Part B: Avelumab
Affected / at Risk (%) Affected / at Risk (%)
Total   43/88 (48.86%)   58/116 (50.00%) 
Hide Serious Adverse Events
Part A: Avelumab Part B: Avelumab
Affected / at Risk (%) Affected / at Risk (%)
Total   36/88 (40.91%)   58/116 (50.00%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/88 (3.41%)  1/116 (0.86%) 
Leukocytosis * 1  1/88 (1.14%)  0/116 (0.00%) 
Microcytic anaemia * 1  1/88 (1.14%)  0/116 (0.00%) 
Normochromic normocytic anaemia * 1  1/88 (1.14%)  0/116 (0.00%) 
Cardiac disorders     
Atrial flutter * 1  1/88 (1.14%)  0/116 (0.00%) 
Pericardial effusion * 1  1/88 (1.14%)  0/116 (0.00%) 
Tachycardia * 1  1/88 (1.14%)  0/116 (0.00%) 
Bundle branch block right * 1  0/88 (0.00%)  1/116 (0.86%) 
Myocarditis * 1  0/88 (0.00%)  1/116 (0.86%) 
Eye disorders     
Eyelid function disorder * 1  1/88 (1.14%)  0/116 (0.00%) 
Glaucoma * 1  1/88 (1.14%)  0/116 (0.00%) 
Retinal artery occlusion * 1  1/88 (1.14%)  0/116 (0.00%) 
Ulcerative keratitis * 1  1/88 (1.14%)  0/116 (0.00%) 
Diplopia * 1  0/88 (0.00%)  1/116 (0.86%) 
Gastrointestinal disorders     
Abdominal pain * 1  2/88 (2.27%)  2/116 (1.72%) 
Enterocolitis * 1  1/88 (1.14%)  0/116 (0.00%) 
Faecaloma * 1  1/88 (1.14%)  0/116 (0.00%) 
Gastric haemorrhage * 1  1/88 (1.14%)  0/116 (0.00%) 
Gastrointestinal haemorrhage * 1  1/88 (1.14%)  0/116 (0.00%) 
Ileus * 1  1/88 (1.14%)  1/116 (0.86%) 
Oesophageal spasm * 1  1/88 (1.14%)  0/116 (0.00%) 
Abdominal pain upper * 1  0/88 (0.00%)  1/116 (0.86%) 
Colitis * 1  0/88 (0.00%)  1/116 (0.86%) 
Diverticulum * 1  0/88 (0.00%)  1/116 (0.86%) 
Dysphagia * 1  0/88 (0.00%)  2/116 (1.72%) 
Faeces discoloured * 1  0/88 (0.00%)  1/116 (0.86%) 
Large intestine perforation * 1  0/88 (0.00%)  1/116 (0.86%) 
Upper gastrointestinal haemorrhage * 1  0/88 (0.00%)  1/116 (0.86%) 
Vomiting * 1  0/88 (0.00%)  2/116 (1.72%) 
General disorders     
Asthenia * 1  2/88 (2.27%)  2/116 (1.72%) 
Chest pain * 1  1/88 (1.14%)  1/116 (0.86%) 
Disease progression * 1  4/88 (4.55%)  10/116 (8.62%) 
Fatigue * 1  1/88 (1.14%)  0/116 (0.00%) 
General physical health deterioration * 1  2/88 (2.27%)  6/116 (5.17%) 
Non-cardiac chest pain * 1  1/88 (1.14%)  0/116 (0.00%) 
Pain * 1  1/88 (1.14%)  0/116 (0.00%) 
Gait disturbance * 1  0/88 (0.00%)  1/116 (0.86%) 
Influenza like illness * 1  0/88 (0.00%)  1/116 (0.86%) 
Multiple organ dysfunction syndrome * 1  0/88 (0.00%)  1/116 (0.86%) 
Pyrexia * 1  0/88 (0.00%)  1/116 (0.86%) 
Hepatobiliary disorders     
Hepatic failure * 1  1/88 (1.14%)  0/116 (0.00%) 
Liver injury * 1  1/88 (1.14%)  0/116 (0.00%) 
Infections and infestations     
Cellulitis * 1  2/88 (2.27%)  0/116 (0.00%) 
Diabetic foot infection * 1  1/88 (1.14%)  0/116 (0.00%) 
Erysipelas * 1  1/88 (1.14%)  0/116 (0.00%) 
Klebsiella sepsis * 1  1/88 (1.14%)  1/116 (0.86%) 
Lung infection * 1  1/88 (1.14%)  1/116 (0.86%) 
Pneumonia * 1  1/88 (1.14%)  1/116 (0.86%) 
Streptococcal sepsis * 1  1/88 (1.14%)  0/116 (0.00%) 
Urinary tract infection * 1  1/88 (1.14%)  1/116 (0.86%) 
Endocarditis * 1  0/88 (0.00%)  1/116 (0.86%) 
Infection * 1  0/88 (0.00%)  1/116 (0.86%) 
Infective exacerbation of bronchiectasis * 1  0/88 (0.00%)  1/116 (0.86%) 
Peritonitis * 1  0/88 (0.00%)  1/116 (0.86%) 
Sepsis * 1  0/88 (0.00%)  4/116 (3.45%) 
Streptococcal infection * 1  0/88 (0.00%)  1/116 (0.86%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  1/88 (1.14%)  3/116 (2.59%) 
Hip fracture * 1  0/88 (0.00%)  1/116 (0.86%) 
Radiation mucositis * 1  0/88 (0.00%)  1/116 (0.86%) 
Radiation skin injury * 1  0/88 (0.00%)  1/116 (0.86%) 
Tendon rupture * 1  0/88 (0.00%)  1/116 (0.86%) 
Investigations     
Transaminases increased * 1  1/88 (1.14%)  0/116 (0.00%) 
Liver function test increased * 1  0/88 (0.00%)  1/116 (0.86%) 
Weight decreased * 1  0/88 (0.00%)  1/116 (0.86%) 
Metabolism and nutrition disorders     
Diabetes mellitus * 1  1/88 (1.14%)  2/116 (1.72%) 
Hyponatraemia * 1  1/88 (1.14%)  3/116 (2.59%) 
Decreased appetite * 1  0/88 (0.00%)  1/116 (0.86%) 
Dehydration * 1  0/88 (0.00%)  2/116 (1.72%) 
Tumour lysis syndrome * 1  0/88 (0.00%)  1/116 (0.86%) 
Musculoskeletal and connective tissue disorders     
Bone pain * 1  1/88 (1.14%)  0/116 (0.00%) 
Chondrocalcinosis * 1  1/88 (1.14%)  0/116 (0.00%) 
Flank pain * 1  1/88 (1.14%)  0/116 (0.00%) 
Musculoskeletal pain * 1  1/88 (1.14%)  0/116 (0.00%) 
Synovitis * 1  1/88 (1.14%)  1/116 (0.86%) 
Arthritis * 1  0/88 (0.00%)  1/116 (0.86%) 
Myopathy * 1  0/88 (0.00%)  1/116 (0.86%) 
Myositis * 1  0/88 (0.00%)  1/116 (0.86%) 
Spondylitis * 1  0/88 (0.00%)  1/116 (0.86%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression * 1  1/88 (1.14%)  2/116 (1.72%) 
Metastases to meninges * 1  1/88 (1.14%)  0/116 (0.00%) 
Neoplasm progression * 1  1/88 (1.14%)  0/116 (0.00%) 
Pericardial effusion malignant * 1  1/88 (1.14%)  0/116 (0.00%) 
Squamous cell carcinoma * 1  1/88 (1.14%)  0/116 (0.00%) 
Squamous cell carcinoma of skin * 1  1/88 (1.14%)  0/116 (0.00%) 
Basal cell carcinoma * 1  0/88 (0.00%)  1/116 (0.86%) 
Bowen's disease * 1  0/88 (0.00%)  1/116 (0.86%) 
Lung adenocarcinoma * 1  0/88 (0.00%)  1/116 (0.86%) 
Metastases to central nervous system * 1  0/88 (0.00%)  2/116 (1.72%) 
Metastasis * 1  0/88 (0.00%)  1/116 (0.86%) 
Paraneoplastic syndrome * 1  0/88 (0.00%)  1/116 (0.86%) 
Prostate cancer * 1  0/88 (0.00%)  1/116 (0.86%) 
Tumour compression * 1  0/88 (0.00%)  1/116 (0.86%) 
Nervous system disorders     
Encephalopathy * 1  1/88 (1.14%)  1/116 (0.86%) 
Post herpetic neuralgia * 1  1/88 (1.14%)  0/116 (0.00%) 
Autoimmune neuropathy * 1  0/88 (0.00%)  1/116 (0.86%) 
Cerebrovascular accident * 1  0/88 (0.00%)  1/116 (0.86%) 
Dizziness * 1  0/88 (0.00%)  1/116 (0.86%) 
Dysarthria * 1  0/88 (0.00%)  1/116 (0.86%) 
Paraneoplastic encephalomyelitis * 1  0/88 (0.00%)  1/116 (0.86%) 
Polyneuropathy * 1  0/88 (0.00%)  1/116 (0.86%) 
Polyneuropathy in malignant disease * 1  0/88 (0.00%)  1/116 (0.86%) 
Transient ischaemic attack * 1  0/88 (0.00%)  1/116 (0.86%) 
Psychiatric disorders     
Anxiety * 1  0/88 (0.00%)  1/116 (0.86%) 
Confusional state * 1  0/88 (0.00%)  1/116 (0.86%) 
Delirium * 1  0/88 (0.00%)  1/116 (0.86%) 
Renal and urinary disorders     
Acute kidney injury * 1  4/88 (4.55%)  1/116 (0.86%) 
Tubulointerstitial nephritis * 1  1/88 (1.14%)  0/116 (0.00%) 
Hydronephrosis * 1  0/88 (0.00%)  3/116 (2.59%) 
Renal impairment * 1  0/88 (0.00%)  1/116 (0.86%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/88 (1.14%)  1/116 (0.86%) 
Dyspnoea exertional * 1  1/88 (1.14%)  0/116 (0.00%) 
Pleural effusion * 1  1/88 (1.14%)  0/116 (0.00%) 
Epiglottic cyst * 1  0/88 (0.00%)  1/116 (0.86%) 
Hypoxia * 1  0/88 (0.00%)  1/116 (0.86%) 
Pleural thickening * 1  0/88 (0.00%)  1/116 (0.86%) 
Pneumonitis * 1  0/88 (0.00%)  1/116 (0.86%) 
Productive cough * 1  0/88 (0.00%)  1/116 (0.86%) 
Pulmonary embolism * 1  0/88 (0.00%)  2/116 (1.72%) 
Respiratory failure * 1  0/88 (0.00%)  1/116 (0.86%) 
Skin and subcutaneous tissue disorders     
Vascular purpura * 1  0/88 (0.00%)  1/116 (0.86%) 
Surgical and medical procedures     
Knee arthroplasty * 1  0/88 (0.00%)  1/116 (0.86%) 
Vascular disorders     
Deep vein thrombosis * 1  1/88 (1.14%)  0/116 (0.00%) 
Superior vena cava syndrome * 1  1/88 (1.14%)  0/116 (0.00%) 
Hypotension * 1  0/88 (0.00%)  1/116 (0.86%) 
Lymphoedema * 1  0/88 (0.00%)  2/116 (1.72%) 
Shock haemorrhagic * 1  0/88 (0.00%)  1/116 (0.86%) 
1
Term from vocabulary, MedDRA v18.1and 22.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: Avelumab Part B: Avelumab
Affected / at Risk (%) Affected / at Risk (%)
Total   86/88 (97.73%)   114/116 (98.28%) 
Blood and lymphatic system disorders     
Anaemia * 1  12/88 (13.64%)  19/116 (16.38%) 
Lymphopenia * 1  6/88 (6.82%)  9/116 (7.76%) 
Eosinophilia * 1  0/88 (0.00%)  6/116 (5.17%) 
Gastrointestinal disorders     
Abdominal pain * 1  9/88 (10.23%)  11/116 (9.48%) 
Constipation * 1  15/88 (17.05%)  29/116 (25.00%) 
Diarrhoea * 1  20/88 (22.73%)  18/116 (15.52%) 
Nausea * 1  18/88 (20.45%)  22/116 (18.97%) 
Vomiting * 1  10/88 (11.36%)  10/116 (8.62%) 
General disorders     
Asthenia * 1  9/88 (10.23%)  24/116 (20.69%) 
Chills * 1  6/88 (6.82%)  14/116 (12.07%) 
Fatigue * 1  32/88 (36.36%)  27/116 (23.28%) 
Oedema peripheral * 1  16/88 (18.18%)  15/116 (12.93%) 
Pyrexia * 1  6/88 (6.82%)  13/116 (11.21%) 
Infections and infestations     
Nasopharyngitis * 1  6/88 (6.82%)  8/116 (6.90%) 
Upper respiratory tract infection * 1  5/88 (5.68%)  8/116 (6.90%) 
Bronchitis * 1  0/88 (0.00%)  7/116 (6.03%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  12/88 (13.64%)  10/116 (8.62%) 
Fall * 1  0/88 (0.00%)  9/116 (7.76%) 
Investigations     
Alanine aminotransferase increased * 1  6/88 (6.82%)  9/116 (7.76%) 
Aspartate aminotransferase increased * 1  5/88 (5.68%)  6/116 (5.17%) 
Blood bilirubin increased * 1  0/88 (0.00%)  6/116 (5.17%) 
Blood creatinine increased * 1  5/88 (5.68%)  10/116 (8.62%) 
Blood creatine phosphokinase increased * 1  0/88 (0.00%)  7/116 (6.03%) 
Lipase increased * 1  0/88 (0.00%)  10/116 (8.62%) 
Weight decreased * 1  12/88 (13.64%)  18/116 (15.52%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  17/88 (19.32%)  16/116 (13.79%) 
Hyperkalaemia * 1  0/88 (0.00%)  9/116 (7.76%) 
Hypomagnesaemia * 1  0/88 (0.00%)  7/116 (6.03%) 
Hyponatraemia * 1  0/88 (0.00%)  11/116 (9.48%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  14/88 (15.91%)  10/116 (8.62%) 
Back pain * 1  9/88 (10.23%)  13/116 (11.21%) 
Muscle spasms * 1  6/88 (6.82%)  0/116 (0.00%) 
Pain in extremity * 1  13/88 (14.77%)  0/116 (0.00%) 
Nervous system disorders     
Dizziness * 1  11/88 (12.50%)  0/116 (0.00%) 
Headache * 1  8/88 (9.09%)  0/116 (0.00%) 
Psychiatric disorders     
Insomnia * 1  6/88 (6.82%)  0/116 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  0/88 (0.00%)  6/116 (5.17%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  15/88 (17.05%)  28/116 (24.14%) 
Dyspnoea * 1  0/88 (0.00%)  16/116 (13.79%) 
Skin and subcutaneous tissue disorders     
Actinic keratosis * 1  0/88 (0.00%)  9/116 (7.76%) 
Dry skin * 1  0/88 (0.00%)  9/116 (7.76%) 
Erythema * 1  0/88 (0.00%)  7/116 (6.03%) 
Pruritus * 1  8/88 (9.09%)  18/116 (15.52%) 
Rash * 1  10/88 (11.36%)  11/116 (9.48%) 
Rash maculo-papular * 1  5/88 (5.68%)  7/116 (6.03%) 
Vascular disorders     
Hypertension * 1  11/88 (12.50%)  11/116 (9.48%) 
1
Term from vocabulary, MedDRA v18.1and 22.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Communication Center
Organization: Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
EMail: service@emdgroup.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
ClinicalTrials.gov Identifier: NCT02155647    
Other Study ID Numbers: 100070-003
2014-000445-79 ( EudraCT Number )
First Submitted: June 2, 2014
First Posted: June 4, 2014
Results First Submitted: April 24, 2020
Results First Posted: July 22, 2020
Last Update Posted: July 22, 2020