Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    KEYNOTE 716
Previous Study | Return to List | Next Study

Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03553836
Recruitment Status : Active, not recruiting
First Posted : June 12, 2018
Last Update Posted : November 12, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk Stage II melanoma. Participants in Part 1 will receive either pembrolizumab or placebo in a double-blind design for up to 17 cycles (each cycle = 21 days). Participants who receive placebo or who stop treatment after receiving 17 cycles of pembrolizumab in Part 1, do not experience disease recurrence within 6 months of completing pembrolizumab in Part 1, and do not stop treatment with pembrolizumab for disease recurrence or intolerability, may be eligible to receive up to 35 additional cycles of pembrolizumab in Part 2 in an open-label design. The primary hypothesis of this study is that pembrolizumab increases recurrence-free survival (RFS) compared to placebo.

Condition or disease Intervention/treatment Phase
Melanoma Biological: Pembrolizumab Other: Placebo Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 954 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716)
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : October 26, 2022
Estimated Study Completion Date : October 12, 2033

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Pembrolizumab
Pediatric participants receive 2 mg/kg (200 mg maximum) pembrolizumab by intravenous (IV) infusion every 3 weeks (Q3W; 21-day cycles) for up to 17 cycles (up to ~1 year) in a double-blind design in Part 1. Adult participants receive 200 mg pembrolizumab by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to ~1 year) in a double-blind design in Part 1. Participants that complete 17 cycles of pembrolizumab and experience disease recurrence may be eligible to receive additional cycles of pembrolizumab in Part 2 in an open-label design. In Part 2, participants will receive up to 17 cycles (up to ~1 year) of pembrolizumab for local/distant recurrence following disease resection or up to 35 cycles (up to ~2 years) of pembrolizumab for unresectable disease recurrence. Participants with distant metastasis who undergo complete resection will receive 17 cycles (up to ~1 year) of pembrolizumab but can receive up to 35 cycles (up to ~2 years) of pembrolizumab under certain circumstances.
 Biological: Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475
Placebo Comparator: Placebo
Participants receive saline placebo by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to ~1 year) in a double-blind design in Part 1. Participants that complete 17 cycles of placebo and experience disease recurrence may be eligible to receive pembrolizumab in Part 2 in an open-label design. In Part 2, participants will receive up to 17 cycles (up to ~1 year) of pembrolizumab for local/distant recurrence following disease resection or up to 35 cycles (up to ~2 years) of pembrolizumab for disease that cannot be resected or metastatic disease.
 Biological: Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Other: Placebo
Administered as an IV infusion every 3 weeks (Q3W)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Recurrence-free Survival (RFS) [ Time Frame: Up to 4 Years ]
    RFS is defined as the time from randomization to any of the following events: recurrence of melanoma at any site (local, in-transit or regional lymph nodes or distant recurrence) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause.


Secondary Outcome Measures :
  1. Distant Metastasis-free Survival (DMFS) [ Time Frame: Up to 9 Years ]
    DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis per RECIST 1.1. Distant metastasis refers to cancer that has spread from the original (primary) tumor and beyond local tissues and lymph nodes to distant organs or distant lymph nodes.

  2. Overall Survival (OS) [ Time Frame: Up to 15 Years ]
    OS is the time from randomization to death due to any cause.

  3. Incidence of Adverse Events (AEs) [ Time Frame: From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 39 months) ]
    Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.

  4. Incidence of Discontinuations [ Time Frame: From time of signing the ICF until the end of study treatment (up to approximately 36 months) ]
    Percentage of participants discontinuing study drug due to an AE.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion:

  • Has surgically resected and histologically/pathologically confirmed new diagnosis of Stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer (AJCC) 8th edition guidelines
  • Has not been previously treated for melanoma beyond complete surgical resection
  • Has ≤12 weeks between final surgical resection and randomization
  • Has no evidence of metastatic disease on imaging as determined by investigator
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or Lansky Play-Performance Scale (LPS) score ≥50 for participants ≤16 years old, or a Karnofsky Performance Scale (KPS) score ≥50 for participants >16 and <18 years old
  • Has recovered adequately from toxicity and/or complications from surgery prior to study start
  • Female participants must not be pregnant or breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment if they are a woman of childbearing potential (WOCBP)

Exclusion:

  • Has a known additional malignancy that is progressing or has required active antineoplastic therapy (including hormonal) within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Has recovered adequately from major surgery or the toxicity and/or complications from the intervention prior to starting study treatment
  • WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Has received prior therapy with an 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 with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
  • Has received prior systemic anti-cancer therapy for melanoma including investigational agents
  • Has received a live vaccine within 30 days prior to the first dose of study treatment
  • 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 the first dose of study treatment
  • Has severe hypersensitivity (≥Grade 3) to any excipients of pembrolizumab
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has a history of (noninfectious) 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 reactive) or known active Hepatitis C virus (defined as Hepatitis C virus ribonucleic acid ((RNA)) [qualitative] is detected) infection
  • Has a history of active tuberculosis (Bacillus tuberculosis)
  • 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 had an allogeneic tissue/solid organ transplant
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03553836


Locations
Show Show 159 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03553836    
Other Study ID Numbers: 3475-716
2018-000669-35 ( EudraCT Number )
MK-3475-716 ( Other Identifier: Merck Protocol Number )
KEYNOTE-716 ( Other Identifier: Merck )
205203 ( Registry Identifier: JAPIC-CTI )
First Posted: June 12, 2018    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: November 2020
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

Layout table for additional information
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 (PD1)
Programmed Cell Death Receptor 1 (PD-1)
Programmed Cell Death Receptor Ligand 1 (PDL1)
Programmed Cell Death Receptor Ligand 1 (PD-L1)
Additional relevant MeSH terms:
Layout table for 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, Immunological
Antineoplastic Agents