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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03553836




Registration number
NCT03553836
Ethics application status
Date submitted
1/06/2018
Date registered
12/06/2018
Date last updated
21/09/2020

Titles & IDs
Public title
Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)
Scientific title
Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716)
Secondary ID [1] 0 0
2018-000669-35
Secondary ID [2] 0 0
3475-716
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Other interventions - Placebo

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 unresectable disease recurrence. Participants with distant metastasis who undergo complete resection will receive 17 cycles of pembrolizumab but can receive up to 35 cycles of pembrolizumab under certain circumstances.

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.


Other interventions: Pembrolizumab
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

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

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-free Survival (RFS) - 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.
Timepoint [1] 0 0
Up to 4 Years
Secondary outcome [1] 0 0
Distant Metastasis-free Survival (DMFS) - 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.
Timepoint [1] 0 0
Up to 9 Years
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is the time from randomization to death due to any cause.
Timepoint [2] 0 0
Up to 15 Years
Secondary outcome [3] 0 0
Incidence of Adverse Events (AEs) - 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.
Timepoint [3] 0 0
From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 39 months)
Secondary outcome [4] 0 0
Incidence of Discontinuations - Percentage of participants discontinuing study drug due to an AE.
Timepoint [4] 0 0
From time of signing the ICF until the end of study treatment (up to approximately 36 months)

Eligibility
Key inclusion 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

- 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)
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia ( Site 0856) - North Sydney
Recruitment hospital [2] 0 0
Westmead Hospital ( Site 0853) - Westmead
Recruitment hospital [3] 0 0
Cairns Base Hospital ( Site 0859) - Cairns
Recruitment hospital [4] 0 0
Tasman Oncology Research Pty Ltd ( Site 0858) - Southport
Recruitment hospital [5] 0 0
Princess Alexandra Hospital ( Site 0857) - Woolloongabba
Recruitment hospital [6] 0 0
Royal Adelaide Hospital ( Site 0861) - Adelaide
Recruitment hospital [7] 0 0
Ashford Cancer Centre Research ( Site 0860) - Kurralta Park
Recruitment hospital [8] 0 0
The Alfred Hospital ( Site 0852) - Melbourne
Recruitment hospital [9] 0 0
Fiona Stanley Hospital ( Site 0851) - Murdoch
Recruitment postcode(s) [1] 0 0
2065 - North Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4870 - Cairns
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Colorado
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Connecticut
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Florida
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Georgia
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Illinois
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Iowa
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Maryland
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Michigan
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Ohio
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Oregon
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Wisconsin
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Antwerpen
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Bayern
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Thuringen
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Mazowieckie
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Slaskie
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Gauteng
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South Africa
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Western Cape
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Spain
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Gipuzkoa
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Spain
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Valenciana, Comunitat
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Barcelona
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Berne
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Geneve
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Grisons
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Switzerland
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Vaud
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Wallis
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Zürich
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Cambridgeshire
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London, City Of
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Surrey
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United Kingdom
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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. 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.
Trial website
https://clinicaltrials.gov/show/NCT03553836
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03553836