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

NCT ID: NCT02155647

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-03
• Study Completion Date: 2023-05-03

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).

Conditions

Carcinoma, Merkel Cell

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

anti-PD-L1; MSB0010718C

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

UCLA Medical Center

Los Angeles, California, United States

The Angeles Clinic and Research Institute - West LA

Los Angeles, California, United States

University of Colorado

Aurora, Colorado, United States

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

National Cancer Institute

Bethesda, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Mount Sinai

New York, New York, United States

Peggy & Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Tasman Oncology Research Ltd

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

St John of God Subiaco Hospital

Perth, Western Australia, Australia

CHU Nice - Hopital de l Archet 2

Nice, Alpes Maritimes, France

Hôpital de la Timone

Marseille, Bouches-du-Rhône, France

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs, France

CHU Nantes - Hôtel Dieu

Nantes, Loire Atlantique, France

Hopital Claude Huriez - CHU Lille

Lille, Nord, France

Hôpital Saint-Louis

Paris, Paris, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, Rhone, France

Institut Gustave Roussy

Villejuif, Val De Marne, France

Groupe Hospitalier Saint André - Hôpital Saint André

Bordeaux, , France

Hôpital Ambroise Paré - Boulogne-Billancourt

Boulogne-Billancourt, , France

CHU Tours - Hôpital Trousseau

Chambray-lès-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

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt am Main, Hesse, Germany

St. Josef-Hospital Universitaetsklinikum

Bochum, North Rhine-Westphalia, Germany

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, Germany

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Fachklinik Hornheide

Münster, North Rhine-Westphalia, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, Germany

Universitaetsklinikum Schleswig-Holstein - Klinik fuer Allgemeine Innere Medizin

Kiel, Schleswig-Holstein, Germany

Universitaetsklinikum Schleswig Holstein - Campus Luebeck

Lübeck, Schleswig-Holstein, Germany

Helios Klinikum Erfurt

Erfurt, Thuringia, Germany

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, , Germany

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

IEO Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori Fondazione G.Pascale

Napoli, , Italy

IOV - Istituto Oncologico Veneto IRCCS

Padua, , Italy

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, , Italy

Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, , Italy

Istituto Nazionale Tumori Regina Elena IRCCS

Roma, , Italy

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

Siena, , Italy

Shizuoka Cancer Center

Shizuoka, Shizuoka, Japan

National Cancer Center Hospital

Chūōku, , Japan

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

Countries

United States; Australia; France; Germany; Italy; Japan; Spain

References

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.

Reference Type: RESULT

PMID: 27592805 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29347993 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29566106 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32414862 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32472503 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29512061 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29273043 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33219092 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32938212 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34921021 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34301810 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32430019 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32375680 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31553054 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29914528 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=100070-003

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

2014-000445-79

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

100070-003

Identifier Type: -

Identifier Source: org_study_id