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Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Pembrolizumab
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring PD1, PD-1, PDL1, PD-L1

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • At least one measurable lesion
  • Adequate organ function

Exclusion criteria:

  • Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent
  • Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study
  • Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (<= Grade 1 or baseline) from adverse events due to a previously administered agent
  • Expected to require any other form of systemic or localized antineoplastic therapy while in study
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
  • Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment
  • Received a live vaccine within 4 weeks prior to the first dose of trial treatment
  • Has a known hypersensitivity to the components of the study drug or another monoclonal antibody
  • History or evidence of active pneumonitis
  • Human immunodeficiency virus (HIV)-positive
  • Has known history of active Hepatitis B or C
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial treatment through 120 days after the last dose of study medication

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Advanced Cutaneous Melanoma

    Advanced Mucosal Melanoma

    Arm Description

    Participants with advanced cutaneous melanoma received pembrolizumab, 2 mg/kg, intravenously (IV) over 30 minutes on Day 1 of each 3-week dosing cycle (Q3W).

    Participants with advanced mucosal melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W.

    Outcomes

    Primary Outcome Measures

    Number of Participants Experiencing Adverse Events (AEs)
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
    Number of Participants Discontinuing Treatment Due to AEs
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
    Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    The ORR, using RECIST 1.1, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review.

    Secondary Outcome Measures

    ORR Per Investigator Assessment Using RECIST 1.1
    The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.
    ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC)
    The ORR, using irRC, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (irCR; complete disappearance of all tumor lesions, whether measureable or not, and no new lesions) or a Partial Response (irPR; decrease in sum of the products of the 2 largest perpendicular diameters of 50% or greater) at any time during the study, based on central radiology review.

    Full Information

    First Posted
    July 1, 2014
    Last Updated
    March 20, 2020
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02180061
    Brief Title
    Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)
    Official Title
    Phase Ib Study of MK-3475 in Subjects With Advanced Melanoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    July 15, 2014 (Actual)
    Primary Completion Date
    August 31, 2017 (Actual)
    Study Completion Date
    August 31, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.
    Detailed Description
    Participants who discontinue pembrolizumab after achieving a complete response (CR) and subsequently develop progressive disease (PD) may be eligible to enter a Second Course Phase and receive pembrolizumab again. The end of the study for each participant will occur with: 1) the marketing approval of pembrolizumab for melanoma, 2) the completion of safety follow up or 3) the time when a possibility of entry to second course of treatment is lost, whichever occurs last.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Melanoma
    Keywords
    PD1, PD-1, PDL1, PD-L1

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    42 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Advanced Cutaneous Melanoma
    Arm Type
    Experimental
    Arm Description
    Participants with advanced cutaneous melanoma received pembrolizumab, 2 mg/kg, intravenously (IV) over 30 minutes on Day 1 of each 3-week dosing cycle (Q3W).
    Arm Title
    Advanced Mucosal Melanoma
    Arm Type
    Experimental
    Arm Description
    Participants with advanced mucosal melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W.
    Intervention Type
    Biological
    Intervention Name(s)
    Pembrolizumab
    Other Intervention Name(s)
    MK-3475
    Intervention Description
    IV infusion
    Primary Outcome Measure Information:
    Title
    Number of Participants Experiencing Adverse Events (AEs)
    Description
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
    Time Frame
    All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months)
    Title
    Number of Participants Discontinuing Treatment Due to AEs
    Description
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
    Time Frame
    Up to last dose of study drug (Up to 24 months)
    Title
    Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    Description
    The ORR, using RECIST 1.1, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review.
    Time Frame
    Up to 24 months
    Secondary Outcome Measure Information:
    Title
    ORR Per Investigator Assessment Using RECIST 1.1
    Description
    The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.
    Time Frame
    Up to 24 months
    Title
    ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC)
    Description
    The ORR, using irRC, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (irCR; complete disappearance of all tumor lesions, whether measureable or not, and no new lesions) or a Partial Response (irPR; decrease in sum of the products of the 2 largest perpendicular diameters of 50% or greater) at any time during the study, based on central radiology review.
    Time Frame
    Up to 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion criteria: Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 At least one measurable lesion Adequate organ function Exclusion criteria: Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (<= Grade 1 or baseline) from adverse events due to a previously administered agent Expected to require any other form of systemic or localized antineoplastic therapy while in study Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment Received a live vaccine within 4 weeks prior to the first dose of trial treatment Has a known hypersensitivity to the components of the study drug or another monoclonal antibody History or evidence of active pneumonitis Human immunodeficiency virus (HIV)-positive Has known history of active Hepatitis B or C Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial treatment through 120 days after the last dose of study medication
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    28283736
    Citation
    Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, Kiyohara Y, Uhara H, Nakagawa K, Furukawa H, Wada H, Noguchi K, Shimamoto T, Yokota K. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017 Apr;79(4):651-660. doi: 10.1007/s00280-016-3237-x. Epub 2017 Mar 11.
    Results Reference
    result
    Links:
    URL
    http://merckoncologyclinicaltrials.com
    Description
    Merck Oncology Clinical Trials Information

    Learn more about this trial

    Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)

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