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Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/KEYNOTE-054)

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ClinicalTrials.gov Identifier: NCT02362594
Recruitment Status : Active, not recruiting
First Posted : February 13, 2015
Last Update Posted : June 12, 2018
Sponsor:
Collaborator:
European Organisation for Research and Treatment of Cancer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This study will assess whether post-resection adjuvant therapy with pembrolizumab improves recurrence-free survival (RFS) as compared to placebo for high-risk participants with melanoma (Stage IIIA [> 1 mm metastasis], IIIB and IIIC). The study will also assess whether pembrolizumab improves RFS versus placebo in the subgroup of participants with programmed cell death ligand 1 (PD-L1)-positive tumor expression. Participants will be stratified for stage of disease and region and then will be randomly assigned to receive either pembrolizumab or placebo.

An interim analysis of efficacy is planned after approximately 330 RFS events have been reported and will be based on efficacy in the intention to treat population (primary efficacy population). If the superiority of pembrolizumab compared to placebo is confirmed, the final analysis will occur immediately after the interim analysis. The study will continue until 409 RFS events have been reported if superiority is not confirmed.


Condition or disease Intervention/treatment Phase
Melanoma Biological: pembrolizumab Other: placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1019 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Adjuvant Immunotherapy With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK- 3475) Versus Placebo After Complete Resection of High-risk Stage III Melanoma: A Randomized, Double- Blind Phase 3 Trial of the EORTC Melanoma Group
Actual Study Start Date : July 16, 2015
Actual Primary Completion Date : January 8, 2018
Estimated Study Completion Date : July 19, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 1 year
Biological: pembrolizumab
Other Names:
  • KEYTRUDA®
  • MK-3475

Placebo Comparator: Placebo
Participants receive placebo IV on Day 1 of each 21-day cycle for up to 1 year
Other: placebo
Locally sourced placebo




Primary Outcome Measures :
  1. Recurrence-free survival (RFS) for All Participants [ Time Frame: Up to 3 years from first participant in ]
  2. RFS for Participants with PD-L1-positive Tumor Expression [ Time Frame: Up to 3 years from first participant in ]

Secondary Outcome Measures :
  1. Distant Metastases-free Survival (DMFS) in All Participants [ Time Frame: Up to 5 years from first participant in ]
  2. DMFS for Participants with PD-L1-positive Tumor Expression [ Time Frame: Up to 5 years from first participant in ]
  3. Overall Survival (OS) in All Participants [ Time Frame: Up to 8.5 years from first participant in ]
  4. OS in for Participants with PD-L1-positive Tumor Expression [ Time Frame: Up to 8.5 years from first participant in ]


Information from the National Library of Medicine

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

Inclusion criteria:

  • Completely resected Stage III melanoma
  • Tumor tissue available for evaluation of PD-L1 expression
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function
  • No prior therapy for melanoma except surgery for primary melanoma lesions (or previously treated with interferon for thick primary melanomas without evidence of lymph node involvement are eligible)
  • Female participants of childbearing potential should be willing to use adequate methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
  • Male participants should agree to use an adequate method of birth control starting with the first dose of study therapy through 120 days after the last dose of study medication

Exclusion criteria:

  • Mucosal or ocular melanoma
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • History of or current interstitial lung disease
  • History of hematologic or primary solid tumor malignancy, unless no evidence of that disease for 5 years
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Active infection requiring therapy
  • Unstable hyperthyroidism or hypothyroidism
  • Diagnosis of immunodeficiency
  • Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
  • Known history of human immunodeficiency virus (HIV), active Hepatitis B or C
  • Treatment with live vaccine within 30 days prior to the first dose of study medication are not eligible
  • Prior treatment with any anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody or anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent, or prior participation in any Merck pembrolizumab clinical trial
  • Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study medication
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study medication
  • Patient is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial without prospective Institutional Review Board approval (by chair or designee) is given

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): NCT02362594


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
European Organisation for Research and Treatment of Cancer
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02362594     History of Changes
Other Study ID Numbers: 3475-054
1325-MG ( Other Identifier: EORTC study number )
2014-004944-37 ( EudraCT Number )
163277 ( Registry Identifier: JAPIC-CTI )
First Posted: February 13, 2015    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

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.:
PD-1
PD1
Programmed Cell Death-1
Programmed Cell Death 1
Programmed Cell Death-Ligand 1 (PD-L1)
Programmed Cell Death-Ligand 2 (PD-L2)
PDL1
PDL2

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Antineoplastic Agents