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 Description

Brief Summary:

This is a multicenter, international, single-arm, open-label, Phase 2 trial to evaluate the efficacy and safety of avelumab in participants with metastatic Merkel cell carcinoma (MCC).

Condition or disease	Intervention/treatment	Phase
Carcinoma, Merkel Cell	Drug: Avelumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 204 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open-Label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab (MSB0010718C) in Subjects With Merkel Cell Carcinoma
• Actual Study Start Date: July 3, 2014
• Actual Primary Completion Date: May 2, 2019
• Actual Study Completion Date: May 3, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Avelumab; Avelumab was administered 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.; Other Names: anti-PD-L1; MSB0010718C
Experimental: 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.	Drug: Avelumab; Avelumab was administered 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.; Other Names: anti-PD-L1; MSB0010718C

Outcome Measures

Primary Outcome Measures :

1. Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Up to 113 weeks ]
   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.
2. Part B: Durable Response Rate (DRR) [ Time Frame: Up to 161 weeks ]
   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.

Secondary Outcome Measures :

1. Part A: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Up to 325 weeks ]
   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.
2. Part A: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Up to 325 weeks ]
   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.
3. 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 [ Time Frame: Up to 325 weeks ]
   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.
4. Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 325 weeks ]
   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.
5. Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 325 weeks ]
   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.
6. Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) [ Time Frame: Up to 325 weeks ]
   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.
7. Part A: Interim Analysis: Overall Survival (OS) Time [ Time Frame: Up to 87 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 3 Mar 2016) ]
   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.
8. Part A: Final Analysis: Overall Survival (OS) Time [ Time Frame: Time from first administration of trial treatment until death (Up to 325 weeks) ]
   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.
9. Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months [ Time Frame: At Month 6 and 12 ]
   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.
10. Part A: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies [ Time Frame: 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.
11. Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab [ Time Frame: Day 1, 43, 85, 169, 253, 337 and 421 ]
    Serum concentration at end of infusion (CEOI) of Avelumab is reported.
12. Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb [ Time Frame: Day 15, 29, 43, 57, 71, 85, 99, 169, 211, 253, 337 and 421 ]
    Minimum serum post-dose (Ctrough) concentration of avelumab was reported.
13. Part B: Interim Analysis: Overall Survival (OS) Time [ Time Frame: Up to 161 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 2 May 2019) ]
    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).
14. Part B: Final Analysis: Overall Survival (OS) Time [ Time Frame: Time from first administration of trial treatment until death (Up to 396 weeks) ]
    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).
15. Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Up to 396 weeks ]
    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.
16. Part B: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Up to 396 weeks ]
    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.
17. Part B: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Up to 396 weeks ]
    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.
18. 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 [ Time Frame: Up to 396 weeks ]
    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.
19. Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months [ Time Frame: At Month 6 and 12 ]
    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.
20. Part B: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies [ Time Frame: Up to 161 weeks ]
    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.
21. Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab [ Time Frame: At Day 1, 43 and 169 ]
    Serum concentration at end of infusion (CEOI) of Avelumab is reported.
22. Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb [ 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 ]
    Minimum serum post-dose (Ctrough) concentration of avelumab was reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed written informed consent
• Age 18 years and above
• Histologically proven MCC
• Participants must have received at least 1 line of chemotherapy for metastatic MCC and must have progressed after the most recent line of chemotherapy
• For Part B - Participants 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
• Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST Version 1.1 (including skin lesions)
• Adequate hematological, hepatic and renal function (renal function considered adequate as per protocol definition)
• Highly effective contraception for both male and female participants, if the risk of conception exists
• Fresh Biopsy or Archival Tumor Tissue
• Estimated life expectancy of more than 12 weeks

Exclusion Criteria:

• Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted)
• Concurrent treatment with a non permitted drug
• Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (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
• 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
• Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the participant has not fully recovered from the surgery within 4 weeks
• 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 immune-related adverse events [irAE]) while on study is allowed. Also, participants 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. Note: Participants receiving bisphosphonate or denosumab are eligible.
• Participants with active central nervous system (CNS) metastases are excluded. Participants 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
• Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin and for Part A cervical carcinoma in situ or for Part B carcinoma in situ (skin, bladder, cervical, colorectal, breast or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer)
• Prior organ transplantation, including allogeneic stem-cell transplantation
• 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).
• Active or history of any autoimmune disease (except for participants with vitiligo) or immunodeficiencies that required treatment with systemic immunosuppressive drugs
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to (>=) 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v 4.0; however, sensory neuropathy Grade <= 2 is acceptable 14. Pregnancy or lactation
• Known alcohol or drug abuse
• 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
• All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the participant's tolerance of trial treatment
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Legal incapacity or limited legal capacity
• Non oncology 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)

Contacts and Locations

Locations

United States, California

UCLA Medical Center

Los Angeles, California, United States, 90024

The Angeles Clinic and Research Institute - West LA

Los Angeles, California, United States, 90025

United States, Colorado

University of Colorado

Aurora, Colorado, United States, 80045

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States, 33612

United States, Maryland

National Cancer Institute

Bethesda, Maryland, United States, 20892

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215-5418

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08901-1914

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10021

Mount Sinai

New York, New York, United States, 10029

United States, Oklahoma

Peggy & Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

United States, Washington

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

Australia, New South Wales

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia, 2444

Royal North Shore Hospital

St Leonards, New South Wales, Australia, 2065

Australia, Queensland

Tasman Oncology Research Ltd

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia, 4102

Australia, Victoria

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia, 3128

Australia, Western Australia

St John of God Subiaco Hospital

Perth, Western Australia, Australia, 6000

France

CHU Nice - Hopital de l Archet 2

Nice cedex 3, Alpes Maritimes, France, 06202

Hôpital de la Timone

Marseille cedex 05, Bouches-du-Rhône, France, 13385

CHU Besançon - Hôpital Jean Minjoz

Besançon Cedex, Doubs, France, 25030

CHU Nantes - Hôtel Dieu

Nantes Cedex 1, Loire Atlantique, France, 44093

Hopital Claude Huriez - CHU Lille

Lille cedex, Nord, France, 59037

Hôpital Saint-Louis

Paris Cedex 10, Paris, France, 75475

Centre Hospitalier Lyon Sud

Pierre Benite cedex, Rhone, France, 69495

Institut Gustave Roussy

Villejuif cedex, Val De Marne, France, 94805

Groupe Hospitalier Saint André - Hôpital Saint André

Bordeaux, France

Hôpital Ambroise Paré - Boulogne-Billancourt

Boulogne Billancourt, France

CHU Tours - Hôpital Trousseau

Chambray Les Tours, France

CHU de Dijon - Hopital du Bocage

Dijon, France

CHU de Grenoble - Hôpital A Michallon

Grenoble, France

CHU de Limoges - Hôpital Dupuytren

Limoges, France

Germany

Universitaetsklinikum Heidelberg

Heidelberg, Baden Wuerttemberg, Germany, 69120

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, Hessen, Germany, 60590

St. Josef-Hospital Universitaetsklinikum

Bochum, Nordrhein Westfalen, Germany, 44791

Universitaetsklinikum Essen

Essen, Nordrhein Westfalen, Germany, 45122

Universitaetsklinikum Koeln

Koeln, Nordrhein Westfalen, Germany, 50937

Fachklinik Hornheide

Muenster, Nordrhein Westfalen, Germany, 48157

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Sachsen, Germany, 01307

Universitaetsklinikum Schleswig-Holstein - Klinik fuer Allgemeine Innere Medizin

Kiel, Schleswig Holstein, Germany, 24105

Universitaetsklinikum Schleswig Holstein - Campus Luebeck

Luebeck, Schleswig Holstein, Germany, 23538

Helios Klinikum Erfurt

Erfurt, Thueringen, Germany, 99089

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, Germany, 10117

Italy

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy, 10060

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, Italy, 20133

IEO Istituto Europeo di Oncologia

Milano, Italy, 20141

Istituto Nazionale Tumori Fondazione G.Pascale

Napoli, Italy, 80131

IOV - Istituto Oncologico Veneto IRCCS

Padova, Italy, 35128

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, Italy, 06156

Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, Italy, 42100

Istituto Nazionale Tumori Regina Elena IRCCS

Roma, Italy, 00144

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, Italy, 53100

Japan

Shizuoka Cancer Center

Shizuoka, Shizuoka-Ken, Japan, 411-8777

National Cancer Center Hospital

Chuo-ku, Japan

Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain, 08036

Hospital General Universitario Gregorio Marañon

Madrid, Spain, 28007

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital General Universitario de Valencia

Valencia, Spain, 46014

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.

Investigators

• Study Director: Medical Responsible; Merck KGaA, Darmstadt, Germany

  Study Documents (Full-Text)

Documents provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Study Protocol  [PDF] May 25, 2018

Statistical Analysis Plan  [PDF] March 31, 2016

More Information

Additional Information:

Trial Awareness and Transparency website 

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 Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT02155647
• Other Study ID Numbers: 100070-003; 2014-000445-79 ( EudraCT Number )
• First Posted: June 4, 2014
• Results First Posted: July 22, 2020
• Last Update Posted: March 13, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• URL: http://bit.ly/IPD21

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Carcinoma, Merkel Cell; MSB0010718C; avelumab; Bavencio; anti PD-L1; JAVELIN Merkel 200

Additional relevant MeSH terms:

Carcinoma, Merkel Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue; Avelumab; Antineoplastic Agents, Immunological; Antineoplastic Agents