Clinical Trials Register

Summary
EudraCT Number:	2014-000445-79
Sponsor's Protocol Code Number:	EMR100070-003
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-22
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2014-000445-79

A.3

Full title of the trial

A Phase II, open-label, multicenter trial to investigate the clinical activity and safety of avelumab (MSB0010718C) in subjects with Merkel cell
carcinoma

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Avelumab in Subjects With Merkel Cell Carcinoma

A.3.2

Name or abbreviated title of the trial where available

JAVELIN Merkel 200

A.4.1

Sponsor's protocol code number

EMR100070-003

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck KGaA
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck KGaA
B.5.2	Functional name of contact point	Communication Centre Merck KGaA
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Strasse 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496151 725200
B.5.5	Fax number	+496151 722000
B.5.6	E-mail	service@merckgroup.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Bavencio
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono Europe Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/15/1590
D.3 Description of the IMP
D.3.1	Product name	Avelumab
D.3.2	Product code	MSB0010718C
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.2	Current sponsor code	Avelumab
D.3.9.3	Other descriptive name	Anti PD-L1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Merkel Cell Carcinoma

E.1.1.1

Medical condition in easily understood language

A rare skin cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10064025
E.1.2	Term	Merkel cell carcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A: The primary objective of the trial is to assess the clinical activity of Avelumab as determined by the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in subjects with metastatic MCC after failing first-line chemotherapy.
Part B: The primary objective is to evaluate the clinical activity of
avelumab as first-line treatment for metastatic or distally recurrent MCC
as determined by the durable response rate (DRR) according to RECIST
1.1 by an IERC.

E.2.2

Secondary objectives of the trial

Part A: Secondary objectives are as follows:
• To assess the duration of response according to RECIST 1.1
• To assess the progression-free survival time (PFS) according to
RECIST 1.1
• To assess the safety profile of avelumab in subjects with MCC
• To assess the overall survival (OS) time
Part B: Secondary objectives are as follows:
•To assess the OS time
•To assess ORR according to RECIST 1.1
•To assess the duration of response according to RECIST 1.1
•To assess the PFS according to RECIST 1.1
•To assess the safety profile of avelumab in subjects with MCC

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Signed written informed consent
• Age 18 years and above
• Histologically proven MCC as defined in the protocol
• For Part A - Progressive disease after receiving 1 line of chemotherapy
for metastatic MCC
• For Part B – Subjects must not have received any prior systemic
treatment for metastatic MCC. Prior chemotherapy treatment in the
adjuvant setting (no clinically detectable disease; no metastatic disease)
is allowable if the end of treatment occurred at least 6 months prior to
study start)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
to 1
• Estimated life expectancy of more than 12 weeks
• Disease must be measurable with at least 1 uni-dimensional
measurable lesion by RECIST Version 1.1 (including skin lesions)
• Adequate haematological and hepatic function.
• Adequate renal function as per protocol definition
• Fresh Biopsy or Archival Tumor Tissue (as per protocol definition for
Part A and Part B)
• Highly effective contraception for both male and female subjects as per
protocol definition if the risk of conception exists.

E.4

Principal exclusion criteria

1.Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted)
2. Concurrent treatment with a nonpermitted drug
3. Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co regulatory targets such as 4-1BB
4. Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent
5. Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the subject has not fully recovered from the surgery within 4 weeks
6. Concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of systemic steroids (that is, for allergic reactions or the management of irAEs) is allowed while on study. Note:
Subjects receiving bisphosphonate or denosumab are eligible. Also,
subjects requiring hormone replacement with corticosteroids for adrenal
insufficiency are eligible if the steroids are administered only for the
purpose of hormonal replacement and at doses ≤ 10 mg or equivalent
prednisone per day.
7. Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy
8. Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
9. Prior organ transplantation, including allogeneic stem-cell transplantation
10. For Part A, Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS) or any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. For Part B, known history of testing positive for HIV or known AIDS in consultation with the Medical Monitor or HBV or HCV
infection at screening (positive HBV surface antigen or HCV RNA if anti-
HCV antibody screening test positive)
11. Active or history of any autoimmune disease (except for subjects with vitiligo) or immunodeficiencies that required treatment with systemic immunosuppressive drugs
12. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partly controlled asthma)
13. Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v 4.0; however, sensory neuropathy Grade ≤ 2 is acceptable
14. Pregnancy or lactation
15. Known alcohol or drug abuse
16. Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident / stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious cardiac arrhythmia requiring medication
17. All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment
18. Any psychiatric condition that would prohibit the understanding or rendering of informed consent
19. Legal incapacity or limited legal capacity
20. Nononcology vaccine therapies for prevention of infectious disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of trial drug administration. Vaccination while on trial is also prohibited except for administration of inactivated vaccines (for example, inactivated seasonal influenza vaccine)

E.5 End points

E.5.1

Primary end point(s)

Part A: Confirmed BOR for each subject, per RECIST 1.1
Part B: Durable response, defined as objective response (CR or PR)
according to RECIST 1.1, with a duration of at least 6 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 3 years

E.5.2

Secondary end point(s)

Part A: Secondary endpoints include:
• Duration of response
• Progression-Free Survival (PFS) Time
• Number of subjects with Treatment-Emergent Adverse Events
according to the National Cancer Institute Common Terminology Criteria
for Adverse Events (NCI-CTCAE) Version 4.
• Overall Survival (OS) Time
Part B: Secondary endpoints include
• OS time
• confirmed BOR per RECIST 1.1
• duration of response according to RECIST 1.1 as determined by an
IERC
• PFS time according to RECIST 1.1 as determined by an IERC
• Number of subjects with Treatment-Emergent Adverse Events
according to the National Cancer Institute Common Terminology Criteria
for Adverse Events (NCI-CTCAE) Version 4
• serum titers of anti-avelumab antibodies, and
• population PK profile of avelumab (sparse sampling)

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy endpoints: Up to 3 years
Safety endpoints: Baseline up to 10 weeks after last dose administration

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Japan

United States

Austria

France

Spain

Switzerland

Germany

Italy

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Five years after the last subject receives the last dose of avelumab or the last subject dies, whichever occurs first. Under some circumstances, subjects may not be followed for 5 years for survival in this study, for example, subjects may be offered to enroll into a rollover study, or the Sponsor may terminate the study early.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

149

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

101

F.4.2.2

In the whole clinical trial

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After a subject has completed the trial or has withdrawn early, usual treatment will be administered, if required, in accordance with the trial site’s standard of care and generally accepted medical practice and depending on the subject’s individual medical needs.
Upon withdrawal from the trial, subjects may receive whatever care they and their physicians agree upon.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-11-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-04-04

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials