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

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ClinicalTrials.gov Identifier: NCT03553836
Recruitment Status : Recruiting
First Posted : June 12, 2018
Last Update Posted : January 11, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

June 1, 2018
June 12, 2018
January 11, 2019
September 12, 2018
October 26, 2022   (Final data collection date for primary outcome measure)
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 Modified Response Evaluation Criteria in Solid Tumors Version 1.1 for immune-based therapeutics (iRECIST 1.1) or death due to any cause.
Same as current
Complete list of historical versions of study NCT03553836 on ClinicalTrials.gov Archive Site
  • 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 iRECIST 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.
  • Overall Survival (OS) [ Time Frame: Up to 15 Years ]
    OS is the time from randomization to death due to any cause.
  • 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.
  • 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.
Same as current
Not Provided
Not Provided
 
Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)
Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716)
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. 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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Melanoma
  • 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)
  • Experimental: Pembrolizumab
    Pediatric participants receive up to 17 cycles of 2 mg/kg (200 mg maximum) pembrolizumab by intravenous (IV) infusion every 3 weeks (Q3W) in a double-blind design in Part 1. Adult participants receive up to 17 cycles of 200 mg pembrolizumab by IV infusion Q3W 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 of pembrolizumab for local/distant recurrence following resection of disease or up to 35 cycles of pembrolizumab for disease that cannot be resected or metastatic disease.
    Intervention: Biological: Pembrolizumab
  • Placebo Comparator: Placebo
    Participants receive up to 17 cycles of saline placebo by IV infusion Q3W 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 of pembrolizumab for local/distant recurrence following resection of disease or up to 35 cycles of pembrolizumab for disease that cannot be resected or metastatic disease.
    Interventions:
    • Biological: Pembrolizumab
    • Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
954
Same as current
October 21, 2033
October 26, 2022   (Final data collection date for primary outcome measure)

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 of the current primary melanoma lesion
  • Has ≤12 weeks between surgical resection and first study treatment
  • 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 ≥50 for children up to and including 16 years of age at the time of enrollment
  • Has recovered adequately from toxicity and/or complications from surgery prior to study start
  • Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
  • 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) or surgery treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement, 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 or treatment allocation. 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 co-inhibitory 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 (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 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
  • 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 treatment
  • Has had an allogeneic tissue/solid organ transplant
Sexes Eligible for Study: All
12 Years and older   (Child, Adult, Older Adult)
No
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Australia,   Belgium,   Canada,   Chile,   France,   Israel,   Italy,   Poland,   Spain,   Switzerland,   United Kingdom,   United States
 
 
NCT03553836
3475-716
2018-000669-35 ( EudraCT Number )
MK-3475-716 ( Other Identifier: Merck Protocol Number )
KEYNOTE 716 ( Other Identifier: Merck Secondary Study Name )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP