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

NCT02155647 | Completed Phase 2 Results DMC

• 2 other identifiers: 100070-0032014-000445-79
• Study Type: interventional
• Target: 204
• Locations: 7 countries
• Sites: 61

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1

  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.

  Up to 113 weeks

• Part B: Durable Response Rate (DRR)

  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.

  Up to 161 weeks

Secondary Outcomes (22)

• Part A: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1

  Up to 325 weeks

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

  Up to 325 weeks

• 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

  Up to 325 weeks

• Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)

  Up to 325 weeks

• Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)

  Up to 325 weeks

Study Arms (2)

Part A: Avelumab

EXPERIMENTAL

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

Part B: Avelumab

EXPERIMENTAL

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

Interventions

Avelumab 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.

Also known as: anti-PD-L1, MSB0010718C

Part A: Avelumab; Part B: Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead

Study Sites (61)

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

The Angeles Clinic and Research Institute - West LA

Los Angeles, California, 90025, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, 33612, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5418, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

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

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Peggy & Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Tasman Oncology Research Ltd

Southport, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3128, Australia

Location

St John of God Subiaco Hospital

Perth, Western Australia, 6000, Australia

Location

CHU Nice - Hopital de l Archet 2

Nice, Alpes Maritimes, 06202, France

Location

Hôpital de la Timone

Marseille, Bouches-du-Rhône, 13385, France

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs, 25030, France

Location

CHU Nantes - Hôtel Dieu

Nantes, Loire Atlantique, 44093, France

Location

Hopital Claude Huriez - CHU Lille

Lille, Nord, 59037, France

Location

Hôpital Saint-Louis

Paris, Paris, 75475, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Rhone, 69495, France

Location

Institut Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

Groupe Hospitalier Saint André - Hôpital Saint André

Bordeaux, France

Location

Hôpital Ambroise Paré - Boulogne-Billancourt

Boulogne-Billancourt, France

Location

CHU Tours - Hôpital Trousseau

Chambray-lès-Tours, France

Location

CHU de Dijon - Hopital du Bocage

Dijon, France

Location

CHU de Grenoble - Hôpital A Michallon

Grenoble, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, France

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt am Main, Hesse, 60590, Germany

Location

St. Josef-Hospital Universitaetsklinikum

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Fachklinik Hornheide

Münster, North Rhine-Westphalia, 48157, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 01307, Germany

Location

Universitaetsklinikum Schleswig-Holstein - Klinik fuer Allgemeine Innere Medizin

Kiel, Schleswig-Holstein, 24105, Germany

Location

Universitaetsklinikum Schleswig Holstein - Campus Luebeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Helios Klinikum Erfurt

Erfurt, Thuringia, 99089, Germany

Location

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, 10117, Germany

Location

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, 10060, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori Fondazione G.Pascale

Napoli, 80131, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, 06156, Italy

Location

Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, 42100, Italy

Location

Istituto Nazionale Tumori Regina Elena IRCCS

Roma, 00144, Italy

Location

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

Siena, 53100, Italy

Location

Shizuoka Cancer Center

Shizuoka, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Chūōku, Japan

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Related Publications (15)

• 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.

  PMID: 27592805 RESULT

• 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.

  PMID: 29347993 RESULT

• 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.

  PMID: 29566106 RESULT

• 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.

  PMID: 32414862 RESULT

• 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.

  PMID: 32472503 RESULT

• 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.

  PMID: 29512061 RESULT

• 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.

  PMID: 29273043 RESULT

• 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.

  PMID: 33219092 RESULT

• 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.

  PMID: 32938212 RESULT

• 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.

  PMID: 34921021 DERIVED

• 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.

  PMID: 34301810 DERIVED

• 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.

  PMID: 32430019 DERIVED

• 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.

  PMID: 32375680 DERIVED

• 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.

  PMID: 31553054 DERIVED

• 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.

  PMID: 29914528 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

avelumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2014
• First Posted: June 4, 2014
• Study Start: July 3, 2014
• Primary Completion: May 2, 2019
• Study Completion: May 3, 2023
• Last Updated: March 13, 2024
• Results First Posted: July 22, 2020

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

AU (6); ES (5); IT (9); DE (11); JP (2); US (14); FR (14)