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Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)

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ClinicalTrials.gov Identifier: NCT03783078
Recruitment Status : Not yet recruiting
First Posted : December 20, 2018
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a single-arm, open-label, multicenter, efficacy, and safety study of pembrolizumab in adult and pediatric participants with previously untreated advanced Merkel Cell Carcinoma (MCC). The primary objective of the trial is to assess the objective response rate, as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following administration of pembrolizumab.

Condition or disease Intervention/treatment Phase
Merkel Cell Carcinoma Drug: Pembrolizumab (MK-3475) Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) as First Line Therapy in Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-913)
Estimated Study Start Date : February 21, 2019
Estimated Primary Completion Date : September 13, 2021
Estimated Study Completion Date : June 16, 2032


Arm Intervention/treatment
Experimental: Pembrolizumab
Pembrolizumab (MK-3475) 200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W) intravenous (IV), for up to 35 administrations (approximately 2 years)
Drug: Pembrolizumab (MK-3475)
200 mg (adult participants) or 2 mg/kg (up to 200 mg; pediatric participants) on Day 1 of each 3-week cycle (Q3W). IV, Up to 35 administrations (approximately 2 years)
Other Name: MK-3475




Primary Outcome Measures :
  1. Objective Response (OR) [ Time Frame: Up to approximately 2 years ]
    Percentage of participants who have a best response as complete response (CR) or partial response (PR). A CR is the disappearance of all target lesions; a PR is at least a 30% decrease in the sum of diameters of target lesions; taking as reference the baseline sum diameters per RECIST 1.1 as assessed by blinded independent central review (BICR).


Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    Duration of Response is the time from first response (CR or PR) to subsequent disease progression, or death from any cause, whichever occurs first as assessed by BICR per RECIST 1.1

  2. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    Progression-Free Survival is the time from the first day of study treatment to the first confirmed disease progression or death due to any cause, whichever occurs first.

  3. Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    Overall Survival is the time from the first day of study treatment to death due to any cause.

  4. Percentage of Participants with One or More Adverse events (AEs) [ Time Frame: Up to approximately 2 years ]
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  5. Study Intervention Discontinuation due to AEs [ Time Frame: Up to approximately 2 years ]
    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.



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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be male or female and at least 12 years of age, at the time of signing the informed consent/assent.
  • Have histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV) as per American Joint Committee on Cancer (AJCC) 8th edition guidelines.
  • Have been untreated for advanced or metastatic disease except as follows:

    1. Prior intratumoral therapy will be permitted.
    2. Prior adjuvant or neoadjuvant therapy containing systemic chemotherapy will be permitted if treatment concluded at least 3 months prior to Cycle 1 Day 1 (C1D1).
    3. Prior adjuvant or neoadjuvant therapy containing anti-PD-1/L1 or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy will not be permitted.
  • Have at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria as determined by the local site investigator/radiology assessment.
  • Toxic effect(s) of the most recent prior therapy have resolved to Grade 1 or less (except alopecia).
  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP)
  • OR
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis).
  • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Lansky Play-Performance Scale (LPS) ≥50 for pediatric participants up to and including 16 years of age.
  • Have adequate organ function

Exclusion Criteria:

  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years with certain exceptions.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis with certain exceptions.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to C1D1.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs).
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
  • Has clinically significant cardiac disease within 6 months of C1D1, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  • Has not received standard locoregional therapy with surgery and/or radiation therapy for the treatment of local or locoregional disease. Note: This exclusion criterion does not apply to participants who are diagnosed with unresectable or metastatic MCC.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
  • Has received prior systemic anticancer therapy including investigational agents within 12 weeks prior to C1D1.
  • Has received radiotherapy within 2 weeks prior to start of study intervention.
  • Has received a live vaccine within 30 days prior to C1D1.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to C1D1.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
  • Has had an allogenic tissue/solid organ transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03783078


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03783078     History of Changes
Other Study ID Numbers: 3475-913
MK-3475-913 ( Other Identifier: Merck Protocol Number )
2018-002601-57 ( EudraCT Number )
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
programmed cell death receptor 1 (PD-1)
programmed cell death ligand 1 (PD-L1)
anti-PD-1
anti-PD-L1
Merkel cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Pembrolizumab
Antineoplastic Agents