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

• ClinicalTrials.gov Identifier: NCT02155647
• Recruitment Status: Completed
• First Posted: June 4, 2014
• Results First Posted: July 22, 2020
• Last Update Posted: March 13, 2024
• Sponsor: EMD Serono Research & Development Institute, Inc.
• 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

Participant Flow

Recruitment Details
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
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	88	116
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Part A: Avelumab	Part B: Avelumab	Total
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
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%

Outcome Measures

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
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 113 weeks

Outcome Measure Data

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
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	10 11.4%
Partial Response	19 21.6%
Stable Disease	9 10.2%
Non-complete Response/ Non-progressive Disease	0 0.0%
Progressive Disease	32 36.4%
Not evaluable	18 20.5%

2. Primary Outcome

Title	Part B: Durable Response Rate (DRR)
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

Outcome Measure Data

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
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
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 325 weeks

Outcome Measure Data

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
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	29
Median (Full Range); Unit of Measure: Months
	40.5; (2.8 to 41.5)

4. Secondary Outcome

Title	Part A: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
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 325 weeks

Outcome Measure Data

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
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 45.6)

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
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 325 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part A: Avelumab
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	68 77.3%
Participants with TR-Serious-TEAEs	9 10.2%
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)
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 325 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part A: Avelumab
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)
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 325 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part A: Avelumab
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)
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 325 weeks

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
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	Time from first administration of trial treatment until death (Up to 325 weeks)

Outcome Measure Data

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
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
	12.6; (0.4 to 71.9)

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
Description	Serum concentration at end of infusion (CEOI) of Avelumab is reported.
Time Frame	Day 1, 43, 85, 169, 253, 337 and 421

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part B: Avelumab
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
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	Time from first administration of trial treatment until death (Up to 396 weeks)

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part B: Avelumab
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 65.8)

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
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 396 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part B: Avelumab
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
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 396 weeks

Outcome Measure Data

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
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
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 396 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part B: Avelumab
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
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 396 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part B: Avelumab
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
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

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Part B: Avelumab
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
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

Outcome Measure Data

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
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
Description	Serum concentration at end of infusion (CEOI) of Avelumab is reported.
Time Frame	At Day 1, 43 and 169

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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%)

Adverse Events

Time Frame	Part A: Up to 325 weeks; Part B: Up to 396 weeks
Adverse Event Reporting Description	Adverse events were reported as per MedDRA v21.1 for Part A arm and MedDRA v22.0 for Part B.
Arm/Group Title	Part A: Avelumab	Part B: Avelumab
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	63/88 (71.59%)	72/116 (62.07%)
Serious Adverse Events
	Part A: Avelumab	Part B: Avelumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	48/88 (54.55%)	58/116 (50.00%)
Blood and lymphatic system disorders
Anaemia * 1	4/88 (4.55%)	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%)
Thrombocytopenia * 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%)
Cardiac tamponade * 1	1/88 (1.14%)	0/116 (0.00%)
Endocrine disorders
Diabetes insipidus * 1	1/88 (1.14%)	0/116 (0.00%)
Hypothyroidism * 1	1/88 (1.14%)	0/116 (0.00%)
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	3/88 (3.41%)	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	2/88 (2.27%)	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%)
Abdominal hernia * 1	1/88 (1.14%)	0/116 (0.00%)
Autoimmune colitis * 1	1/88 (1.14%)	0/116 (0.00%)
General disorders
Asthenia * 1	1/88 (1.14%)	2/116 (1.72%)
Chest pain * 1	1/88 (1.14%)	1/116 (0.86%)
Disease progression * 1	9/88 (10.23%)	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%)
Immune system disorders
Autoimmune disorder * 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	2/88 (2.27%)	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%)
Eye infection * 1	1/88 (1.14%)	0/116 (0.00%)
Haematoma infection * 1	1/88 (1.14%)	0/116 (0.00%)
Herpes zoster * 1	1/88 (1.14%)	0/116 (0.00%)
Spinal cord infection * 1	1/88 (1.14%)	0/116 (0.00%)
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%)
Femoral neck fracture * 1	1/88 (1.14%)	0/116 (0.00%)
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%)
Intraocular pressure increased * 1	1/88 (1.14%)	0/116 (0.00%)
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%)
Hypernatraemia * 1	1/88 (1.14%)	0/116 (0.00%)
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%)
Muscle spasms * 1	1/88 (1.14%)	0/116 (0.00%)
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	1/88 (1.14%)	1/116 (0.86%)
Confusional state * 1	1/88 (1.14%)	1/116 (0.86%)
Delirium * 1	1/88 (1.14%)	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%)
Haematuria * 1	1/88 (1.14%)	0/116 (0.00%)
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	1/88 (1.14%)	2/116 (1.72%)
Respiratory failure * 1	0/88 (0.00%)	1/116 (0.86%)
Chronic obstructive pulmonary disease * 1	1/88 (1.14%)	0/116 (0.00%)
Skin and subcutaneous tissue disorders
Vascular purpura * 1	0/88 (0.00%)	1/116 (0.86%)
Diabetic foot * 1	1/88 (1.14%)	0/116 (0.00%)
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 v21.1and 22.0; * Indicates events were collected by non-systematic assessment
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	14/88 (15.91%)	19/116 (16.38%)
Lymphopenia * 1	7/88 (7.95%)	9/116 (7.76%)
Eosinophilia * 1	0/88 (0.00%)	6/116 (5.17%)
Endocrine disorders
Hypothyroidism * 1	6/88 (6.82%)	0/116 (0.00%)
Eye disorders
Vision blurred * 1	5/88 (5.68%)	0/116 (0.00%)
Gastrointestinal disorders
Abdominal pain * 1	11/88 (12.50%)	11/116 (9.48%)
Constipation * 1	16/88 (18.18%)	29/116 (25.00%)
Diarrhoea * 1	23/88 (26.14%)	18/116 (15.52%)
Nausea * 1	24/88 (27.27%)	22/116 (18.97%)
Vomiting * 1	13/88 (14.77%)	10/116 (8.62%)
General disorders
Asthenia * 1	10/88 (11.36%)	24/116 (20.69%)
Chills * 1	10/88 (11.36%)	14/116 (12.07%)
Fatigue * 1	34/88 (38.64%)	27/116 (23.28%)
Oedema peripheral * 1	19/88 (21.59%)	15/116 (12.93%)
Pyrexia * 1	9/88 (10.23%)	13/116 (11.21%)
Infections and infestations
Nasopharyngitis * 1	8/88 (9.09%)	8/116 (6.90%)
Upper respiratory tract infection * 1	6/88 (6.82%)	8/116 (6.90%)
Bronchitis * 1	5/88 (5.68%)	7/116 (6.03%)
Cellulitis * 1	5/88 (5.68%)	0/116 (0.00%)
Sinusitis * 1	5/88 (5.68%)	0/116 (0.00%)
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	7/88 (7.95%)	9/116 (7.76%)
Aspartate aminotransferase increased * 1	7/88 (7.95%)	6/116 (5.17%)
Blood bilirubin increased * 1	0/88 (0.00%)	6/116 (5.17%)
Blood creatinine increased * 1	6/88 (6.82%)	10/116 (8.62%)
Blood creatine phosphokinase increased * 1	7/88 (7.95%)	7/116 (6.03%)
Lipase increased * 1	5/88 (5.68%)	10/116 (8.62%)
Weight decreased * 1	14/88 (15.91%)	18/116 (15.52%)
Weight increased * 1	5/88 (5.68%)	0/116 (0.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	21/88 (23.86%)	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%)
Dehydration * 1	6/88 (6.82%)	0/116 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	16/88 (18.18%)	10/116 (8.62%)
Back pain * 1	13/88 (14.77%)	13/116 (11.21%)
Muscle spasms * 1	7/88 (7.95%)	0/116 (0.00%)
Pain in extremity * 1	17/88 (19.32%)	0/116 (0.00%)
Muscular weakness * 1	7/88 (7.95%)	0/116 (0.00%)
Arthritis * 1	6/88 (6.82%)	0/116 (0.00%)
Myalgia * 1	6/88 (6.82%)	0/116 (0.00%)
Flank pain * 1	5/88 (5.68%)	0/116 (0.00%)
Nervous system disorders
Dizziness * 1	12/88 (13.64%)	0/116 (0.00%)
Headache * 1	10/88 (11.36%)	0/116 (0.00%)
Psychiatric disorders
Insomnia * 1	6/88 (6.82%)	0/116 (0.00%)
Anxiety * 1	7/88 (7.95%)	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	16/88 (18.18%)	28/116 (24.14%)
Dyspnoea * 1	9/88 (10.23%)	16/116 (13.79%)
Skin and subcutaneous tissue disorders
Actinic keratosis * 1	0/88 (0.00%)	9/116 (7.76%)
Dry skin * 1	5/88 (5.68%)	9/116 (7.76%)
Erythema * 1	5/88 (5.68%)	7/116 (6.03%)
Pruritus * 1	12/88 (13.64%)	18/116 (15.52%)
Rash * 1	13/88 (14.77%)	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%)
Lymphoedema * 1	6/88 (6.82%)	0/116 (0.00%)
Hypotension * 1	5/88 (5.68%)	0/116 (0.00%)
1 Term from vocabulary, MedDRA v21.1and 22.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is 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

• Name/Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany
• Phone: +49-6151-72-5200
• EMail: service@emdgroup.com

Publications of Results:

Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbe C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016 Oct;17(10):1374-1385. doi: 10.1016/S1470-2045(16)30364-3. Epub 2016 Sep 1.

Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbe C, Milella M, Brownell I, Lewis KD, Lorch JH, von Heydebreck A, Hennessy M, Nghiem P. Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after >/=1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer. 2018 Jan 19;6(1):7. doi: 10.1186/s40425-017-0310-x.

D'Angelo SP, Russell J, Lebbe C, Chmielowski B, Gambichler T, Grob JJ, Kiecker F, Rabinowits G, Terheyden P, Zwiener I, Bajars M, Hennessy M, Kaufman HL. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial. JAMA Oncol. 2018 Sep 1;4(9):e180077. doi: 10.1001/jamaoncol.2018.0077. Epub 2018 Sep 13.

D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbe C, Lewis KD, Linette GP, Milella M, Georges S, Shah P, Ellers-Lenz B, Bajars M, Guzel G, Nghiem PT. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. 2020 May;8(1):e000674. doi: 10.1136/jitc-2020-000674.

Lambert J, Marrel A, D'Angelo SP, Burgess MA, Chmielowski B, Fazio N, Gambichler T, Grob JJ, Lebbe C, Robert C, Russell J, Guzel G, Bharmal M. Patient Experiences with Avelumab in Treatment-Naive Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial. Patient. 2020 Aug;13(4):457-467. doi: 10.1007/s40271-020-00428-5.

Kaufman HL, Dias Barbosa C, Guillemin I, Lambert J, Mahnke L, Bharmal M. Living with Merkel Cell Carcinoma (MCC): Development of a Conceptual Model of MCC Based on Patient Experiences. Patient. 2018 Aug;11(4):439-449. doi: 10.1007/s40271-018-0301-0.

Bharmal M, Fofana F, Barbosa CD, Williams P, Mahnke L, Marrel A, Schlichting M. Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma. Health Qual Life Outcomes. 2017 Dec 22;15(1):247. doi: 10.1186/s12955-017-0815-5. Erratum In: Health Qual Life Outcomes. 2019 Mar 27;17(1):52.

Kelly K, Manitz J, Patel MR, D'Angelo SP, Apolo AB, Rajan A, Kasturi V, Speit I, Bajars M, Warth J, Gulley JL. Efficacy and immune-related adverse event associations in avelumab-treated patients. J Immunother Cancer. 2020 Nov;8(2):e001427. doi: 10.1136/jitc-2020-001427.

Bharmal M, Nolte S, Lebbe C, Mortier L, Brohl AS, Fazio N, Grob JJ, Pusceddu S, Hanna GJ, Hassel JC, Kiecker F, Ellers-Lenz B, Bajars M, Guzel G, Nghiem P, Hunger M, Schlichting M, Henry-Szatkowski M, D'Angelo SP. Health-related quality of life trajectory of treatment-naive patients with Merkel cell carcinoma receiving avelumab. Future Oncol. 2020 Sep;16(27):2089-2099. doi: 10.2217/fon-2020-0426. Epub 2020 Sep 17.

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

Grisic AM, Xiong W, Tanneau L, Jonsson S, Friberg LE, Karlsson MO, Dai H, Zheng J, Girard P, Khandelwal A. Model-Based Characterization of the Bidirectional Interaction Between Pharmacokinetics and Tumor Growth Dynamics in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab. Clin Cancer Res. 2022 Apr 1;28(7):1363-1371. doi: 10.1158/1078-0432.CCR-21-2662.

D'Angelo SP, Lebbe C, Mortier L, Brohl AS, Fazio N, Grob JJ, Prinzi N, Hanna GJ, Hassel JC, Kiecker F, Georges S, Ellers-Lenz B, Shah P, Guzel G, Nghiem P. First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. J Immunother Cancer. 2021 Jul;9(7):e002646. doi: 10.1136/jitc-2021-002646.

Bharmal M, Nolte S, Henry-Szatkowski M, Hennessy M, Schlichting M. Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naive and previously treated patients with metastatic Merkel cell carcinoma. Health Qual Life Outcomes. 2020 May 19;18(1):145. doi: 10.1186/s12955-020-01402-3.

Bullement A, Willis A, Amin A, Schlichting M, Hatswell AJ, Bharmal M. Evaluation of survival extrapolation in immuno-oncology using multiple pre-planned data cuts: learnings to aid in model selection. BMC Med Res Methodol. 2020 May 6;20(1):103. doi: 10.1186/s12874-020-00997-x.

Novakovic AM, Wilkins JJ, Dai H, Wade JR, Neuteboom B, Brar S, Bello CL, Girard P, Khandelwal A. Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma. Clin Pharmacol Ther. 2020 Mar;107(3):588-596. doi: 10.1002/cpt.1645. Epub 2019 Nov 18.

Bharmal M, Guillemin I, Marrel A, Arnould B, Lambert J, Hennessy M, Fofana F. How to address the challenges of evaluating treatment benefits-risks in rare diseases? A convergent mixed methods approach applied within a Merkel cell carcinoma phase 2 clinical trial. Orphanet J Rare Dis. 2018 Jun 18;13(1):95. doi: 10.1186/s13023-018-0835-1.

• 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: March 13, 2024