Trial Outcomes & Findings for Avelumab in Participants With Merkel Cell Carcinoma (JAVELIN Merkel 200) (NCT NCT02155647)

Last Updated: 2024-03-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

204 participants

Primary outcome timeframe

Up to 113 weeks

Results posted on

2024-03-13

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Part A: Avelumab 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.	Part B: Avelumab 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 Study STARTED	88	116
Overall Study COMPLETED	88	116
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Avelumab n=88 Participants 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.	Part B: Avelumab n=116 Participants 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 n=204 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	66 Participants n=5 Participants	94 Participants n=7 Participants	160 Participants n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	35 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	81 Participants n=7 Participants	146 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	29 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants	75 Participants n=7 Participants	133 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants	12 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	81 Participants n=5 Participants	75 Participants n=7 Participants	156 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	36 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 113 weeks

Population: Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Complete Response	10 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Partial Response	19 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Stable Disease	9 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Non-complete Response/ Non-progressive Disease	0 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Progressive Disease	32 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Not evaluable	18 Participants

PRIMARY outcome

Timeframe: Up to 161 weeks

Population: Full analysis set (FAS) included all participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Durable Response Rate (DRR)	30.2 Percentage of participants Interval 22.0 to 39.4

SECONDARY outcome

Timeframe: Up to 325 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=29 Participants 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.
Part A: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1	40.5 Months Interval 2.8 to 41.5

SECONDARY outcome

Timeframe: Up to 325 weeks

Population: Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1	2.7 Months Interval 0.03 to 45.6

SECONDARY outcome

Timeframe: Up to 325 weeks

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

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
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 Participants with TR-TEAEs	68 Participants
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 Participants with TR-TEAEs leading to Death	0 Participants
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 Participants with TR-Serious-TEAEs	9 Participants

SECONDARY outcome

Timeframe: Up to 325 weeks

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

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Anemia	9 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Lymphocyte count decreased	18 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Neutrophil count decreased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Platelet count decreased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) White blood cell count decreased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hypoalbuminemia	2 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Alkaline phosphatase increased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Alanine aminotransferase increased	3 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Serum amylase increased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Aspartate aminotransferase increased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Blood bilirubin increased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Cholesterol high	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Creatine phosphokinase increased	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Creatinine increased	2 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Chronic kidney disease	3 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Gamma-glutamyltransferase increased	6 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hyperglycemia	7 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hypoglycemia	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hyperkalemia	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hypokalemia	2 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Lipase increased	4 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hypermagnesemia	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hypophosphatemia	3 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hyponatremia	11 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) Hypertriglyceridemia	1 Participants

SECONDARY outcome

Timeframe: Up to 325 weeks

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

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Increased Respiratory Rate	81 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Decreased Respiratory Rate	81 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Body temperature Increased	0 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Weight Increased	57 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Weight Decreased	54 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Increased Heart Rate	83 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Decreased Heart Rate	84 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Increased Systolic Blood Pressure	84 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Decreased Systolic Blood Pressure	84 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Increased Diastolic Blood Pressure	84 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) Decreased Diastolic Blood Pressure	84 Participants

SECONDARY outcome

Timeframe: Up to 325 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=81 Participants 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.
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) PR interval >= 220 ms	16 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) QRS >= 120 ms	12 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) QTcF > 30 ms and <= 60 ms	20 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) QTcF > 60 ms	1 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) QTcB > 30 ms and <= 60 ms	25 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) QTcB > 60 ms	2 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Heart rate <= 50 bpm	3 Participants
Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Heart rate >= 120 bpm	2 Participants

SECONDARY outcome

Timeframe: Up to 87 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 3 Mar 2016)

Population: Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Interim Analysis: Overall Survival (OS) Time	11.3 Months Interval 7.5 to 14.0

SECONDARY outcome

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

Population: Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Final Analysis: Overall Survival (OS) Time	12.6 months Interval 0.4 to 71.9

SECONDARY outcome

Timeframe: At Month 6 and 12

Population: Intent-to-Treat analysis set included all participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months In-response at Month 6	30.7 Percentage of participants
Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months In-response at Month 12	20.7 Percentage of participants
Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months Not in-response at Month 6	69.3 Percentage of participants
Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months Not In-response at Month 12	79.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to 80 weeks

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=82 Participants 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.
Part A: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies	3 Participants

SECONDARY outcome

Timeframe: Day 1, 43, 85, 169, 253, 337 and 421

Population: 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

Serum concentration at end of infusion (CEOI) of Avelumab is reported.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 1	252 Micrograms per milliliter Standard Deviation 129
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 43	266 Micrograms per milliliter Standard Deviation 74.2
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 85	274 Micrograms per milliliter Standard Deviation 57.7
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 169	315 Micrograms per milliliter Standard Deviation 65.0
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 253	318 Micrograms per milliliter Standard Deviation 70.1
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 337	373 Micrograms per milliliter Standard Deviation 48.3
Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 421	453 Micrograms per milliliter Standard Deviation 71.5

SECONDARY outcome

Timeframe: Day 15, 29, 43, 57, 71, 85, 99, 169, 211, 253, 337 and 421

Minimum serum post-dose (Ctrough) concentration of avelumab was reported.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=88 Participants 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.
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 421	61.4 Micrograms per milliliter Standard Deviation 7.79
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 15	23.8 Micrograms per milliliter Standard Deviation 28.4
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 29	26.4 Micrograms per milliliter Standard Deviation 13.7
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 43	32.3 Micrograms per milliliter Standard Deviation 35.8
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 57	32.7 Micrograms per milliliter Standard Deviation 18.8
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 71	33.5 Micrograms per milliliter Standard Deviation 21.1
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 85	45.5 Micrograms per milliliter Standard Deviation 53.6
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 99	40.3 Micrograms per milliliter Standard Deviation 24.0
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 169	43.6 Micrograms per milliliter Standard Deviation 19.6
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 211	57.2 Micrograms per milliliter
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 253	38.4 Micrograms per milliliter Standard Deviation 15.7
Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 337	43.9 Micrograms per milliliter Standard Deviation 23.7

SECONDARY outcome

Timeframe: Up to 161 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 2 May 2019)

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

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).

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Interim Analysis: Overall Survival (OS) Time	20.3 Months Interval 0.5 to 34.9

SECONDARY outcome

Timeframe: Time from first administration of trial treatment until death (Up to 396 weeks)

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

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Final Analysis: Overall Survival (OS) Time	20.3 months Interval 0.5 to 65.8

SECONDARY outcome

Timeframe: Up to 396 weeks

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

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Complete Response	19 Participants
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Partial Response	27 Participants
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Stable Disease	12 Participants
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Non-complete Response/ Non-progressive Disease	1 Participants
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Progressive Disease	48 Participants
Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 Not evaluable	9 Participants

SECONDARY outcome

Timeframe: Up to 396 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=46 Participants 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.
Part B: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1	18.2 Months Interval 1.2 to 28.3

SECONDARY outcome

Timeframe: Up to 396 weeks

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

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1	4.1 Months Interval 0.03 to 29.6

SECONDARY outcome

Timeframe: Up to 396 weeks

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

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
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 Participants with TR-TEAEs	94 Participants
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 Participants with TR-Serious-TEAEs	17 Participants
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 Participants with TR-TEAEs leading to Death	0 Participants

SECONDARY outcome

Timeframe: At Month 6 and 12

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

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months In-response at Month 6	33.6 Percentage of Participants Interval 25.1 to 43.0
Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months In-response at Month 12	26.7 Percentage of Participants Interval 18.9 to 35.7
Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months Not in-response at Month 6	66.4 Percentage of Participants
Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months Not in-response at Month 12	73.3 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 161 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=110 Participants 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.
Part B: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies	8 Participants

SECONDARY outcome

Timeframe: At Day 1, 43 and 169

Population: 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.

Serum concentration at end of infusion (CEOI) of Avelumab is reported.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 1	237 Microgram per milliliter Geometric Coefficient of Variation 31.1
Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 43	244 Microgram per milliliter Geometric Coefficient of Variation 32.1
Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab Day 169	255 Microgram per milliliter Geometric Coefficient of Variation 27.7

SECONDARY outcome

Timeframe: Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505, Day 589, Day 673

Minimum serum post-dose (Ctrough) concentration of avelumab was reported.

Outcome measures

Outcome measures
Measure	Part A: Avelumab n=116 Participants 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.
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 15	22.2 Microgram per milliliter Geometric Coefficient of Variation 57.5
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 29	27.8 Microgram per milliliter Geometric Coefficient of Variation 80.2
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 43	27.5 Microgram per milliliter Geometric Coefficient of Variation 89.4
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 85	29.4 Microgram per milliliter Geometric Coefficient of Variation 130.4
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 127	37.0 Microgram per milliliter Geometric Coefficient of Variation 65.6
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 169	45.6 Microgram per milliliter Geometric Coefficient of Variation 60.3
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 253	39.9 Microgram per milliliter Geometric Coefficient of Variation 53.0
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 337	39.5 Microgram per milliliter Geometric Coefficient of Variation 37.3
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 421	43.6 Microgram per milliliter Geometric Coefficient of Variation 30.3
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 505	41.8 Microgram per milliliter Geometric Coefficient of Variation 30.4
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 589	57.5 Microgram per milliliter Geometric Coefficient of Variation 24.1
Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb Day 673	44.9 Microgram per milliliter Geometric Coefficient of Variation 21.4

Adverse Events

Part A: Avelumab

Serious events: 48 serious events

Other events: 86 other events

Deaths: 63 deaths

Part B: Avelumab

Serious events: 58 serious events

Other events: 114 other events

Deaths: 72 deaths

Serious adverse events

Other adverse events

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place