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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03486873




Registration number
NCT03486873
Ethics application status
Date submitted
29/03/2018
Date registered
3/04/2018
Date last updated
25/06/2020

Titles & IDs
Public title
Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587)
Scientific title
A Multicenter, Open Label, Phase III Extension Trial to Study the Long-term Safety and Efficacy in Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab Trial
Secondary ID [1] 0 0
MK-3475-587
Secondary ID [2] 0 0
3475-587
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Standard of Care (SOC)

Experimental: Pembrolizumab - Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants.

Experimental: Pembrolizumab+SOC (Per Parent Study) - Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle PLUS standard of care (SOC) treatment (or per parent study if there is no SOC) for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants. Participants receiving a pembrolizumab-based combination treatment will receive the dose regimen of the combination drug(s) which is recommended per SOC, or was used in the parent study protocol if there is no SOC recommendation.

Active Comparator: SOC (Per Parent Study) - Participants receive the same non-pembrolizumab SOC treatment (e.g. chemotherapy) they were receiving in the parent study for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants.


Other interventions: Pembrolizumab
200 mg IV infusion

Treatment: Drugs: Standard of Care (SOC)
IV infusion or oral tablets

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - OS is defined as the time from randomization or start of study treatment for non-randomized participants (on the parent study) to death due to any cause. Participants without documented death at the time of analysis will be censored at the date of the last follow-up.
Timepoint [1] 0 0
Up to approximately 10 years
Secondary outcome [1] 0 0
Duration of Response (DOR) Per Evaluation Criteria Used in the Parent Study - DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response on the parent study until earliest date of disease progression or death from any cause, whichever comes first based upon investigator assessment. The DOR will be presented.
Timepoint [1] 0 0
Up to approximately 10 years
Secondary outcome [2] 0 0
Duration of Complete Response (DOCR) Per Evaluation Criteria Used in the Parent Study - DOCR is determined by disease assessment and is defined as the time from the date of complete response (CR) on the parent study until earliest date of disease progression or death from any cause, whichever comes first based upon investigator assessment. The DOCR will be presented.
Timepoint [2] 0 0
Up to approximately 10 years
Secondary outcome [3] 0 0
Serious Adverse Events (SAEs) - A SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience a SAE in this study will be presented.
Timepoint [3] 0 0
Up to approximately 42 months (Up to 90 days after last dose of study treatment)
Secondary outcome [4] 0 0
Adverse Events of Special Interest (AEOSI) - AEOSI for this study include selected preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 for the following higher-level terms: Pneumonitis, Colitis, Hepatitis, Nephritis, Adrenal Insufficiency, Hypophysitis, Hyperthyroidism, Hypothyroidism, Thyroiditis, Type 1 Diabetes Mellitus, Severe Skin Reactions Including Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): or If grade 3 or higher, Uveitis, Pancreatitis, Myositis, Guillain-Barre Syndrome, Myocarditis, Encephalitis, Sarcoidosis, Infusion Reactions and Myasthenic Syndrome. The number of participants who experience an AEOSI in this study will be presented.
Timepoint [4] 0 0
Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary outcome [5] 0 0
Events of Clinical Interest (ECI) - ECIs for this study include: 1) An overdose of Sponsor's product, that is not associated with clinical symptoms or abnormal laboratory results or 2) An elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is =3X the upper limit of normal (ULN) and an elevated total bilirubin lab value that is =2X ULN and, at the same time, an alkaline phosphatase lab value that is <2X ULN, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing. The number of participants who experience an ECI in this study will be presented.
Timepoint [5] 0 0
Up to approximately 40 months (Up to 30 days after last dose of study treatment)

Eligibility
Key inclusion criteria
- Advanced unresectable or metastatic tumor(s)

- Currently enrolled in a Merck-sponsored pembrolizumab study and is receiving study
treatment or in a Follow-up Phase at the time MK-3475-587 is open. The parent studies
must have completed all regulatory requirements and submissions, if any, or have fully
addressed their primary endpoint(s) before all their participants roll over into this
MK-3475-587 extension study.

Additional eligibility criteria for participants who enter Second Course Phase once they
are enrolled on MK-3475-587:

- Has not received any anticancer systemic treatment since the last dose of
pembrolizumab or a pembrolizumab-based combination in First Course Phase

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Demonstrates adequate organ function

- Have resolution of any toxic effect(s) of First Course Phase trial treatment with
pembrolizumab or a pembrolizumab-based combination to Grade 1 or less (except
alopecia) before trial treatment in Second Course Phase is started. If participant
received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered
from the toxicity and/or complications of the intervention.

- Male participant must agree to use contraception during the Second Course Phase study
treatment period and for =120 days, corresponding to time needed to eliminate any
study combination treatment(s), plus 75 days (a spermatogenesis cycle) for study
treatments with evidence of genotoxicity at any dose after the last dose of study
treatment and refrain from donating sperm during this period.

- A female participant is eligible to enroll if she is not pregnant, not breastfeeding,
and =1 of the following conditions applies: A woman of childbearing potential (WOCBP)
who agrees to use contraception during the study treatment period and for =120 days
(corresponding to time needed to eliminate any study combination treatment(s) plus 30
days (a menstruation cycle) for study treatments with risk of genotoxicity.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-There are no exclusion criteria to participate in MK-3475-587.

Participants are excluded from entering Second Course trial treatment once they are
enrolled on MK-3475-587 if any of the following criteria applies:

- Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients

- Has received a live vaccine within 30 days prior to the first dose of Second Course
Phase trial treatment

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the Cycle 1 Day 1 of Second Course
Phase

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with
curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast
cancer that has undergone potentially curative therapy.

- Has known active central nervous system metastases and/or carcinomatous meningitis

- Has an active autoimmune disease that has required systemic treatment in the past 2
years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed.

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis. Note: Participants that experienced pneumonitis during First Course that
did not meet the criteria for permanent discontinuation are eligible.

- NSCLC participants only: Has interstitial lung disease

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has a known history of or is positive for hepatitis B or hepatitis C

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the Second Course Phase eligibility
Visit through 120 days after the last dose of study treatment.

- Has severe cardiovascular disease, i.e., arrhythmias, requiring chronic treatment,
congestive heart failure (New York Heart Association Class III or IV) or symptomatic
ischemic heart disease.

- Has hepatic decompensation (Child-Pugh score >6 [class B and C])

- Has uncontrolled thyroid dysfunction

- Has uncontrolled diabetes mellitus

- Has had an allogeneic tissue/solid organ transplant

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



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,VIC,WA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 3003) - Camperdown
Recruitment hospital [2] 0 0
Mater Hospital Sydney ( Site 3007) - North Sydney
Recruitment hospital [3] 0 0
Melanoma Institute Australia ( Site 3001) - North Sydney
Recruitment hospital [4] 0 0
Calvary Mater Newcastle ( Site 3005) - Waratah
Recruitment hospital [5] 0 0
Westmead Hospital ( Site 3000) - Westmead
Recruitment hospital [6] 0 0
Princess Alexandra Hospital ( Site 3002) - Woolloongabba
Recruitment hospital [7] 0 0
Austin Health-Austin Hospital ( Site 3004) - Heidelberg
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre ( Site 3008) - Melbourne
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital ( Site 3006) - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
2065 - North Sydney
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3000 - Melbourne
Recruitment postcode(s) [9] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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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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United States of America
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Illinois
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Iowa
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United States of America
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Maryland
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Massachusetts
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Minnesota
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Nevada
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New Jersey
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New York
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North Carolina
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Pennsylvania
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Tennessee
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Texas
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Virginia
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United States of America
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Washington
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Austria
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Steiermark
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Austria
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Tirol
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Austria
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Wien
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Belgium
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Bruxelles-Capitale, Region De
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Belgium
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Vlaams-Brabant
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Brazil
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Sao Paulo
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Alberta
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Ontario
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Canada
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Quebec
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Chile
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Region Metropolitana De Santiago
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Colombia
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Valle Del Cauca
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Czechia
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Praha 5
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Denmark
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Finistere
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Gironde
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Nord
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Rhone
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France
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Val-de-Marne
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France
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Paris
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Germany
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Germany
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Thuringen
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Hungary
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Jasz-Nagykun-Szolnok
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Hungary
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Kaposvar
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Israel
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HaMerkaz
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Israel
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HaTsafon
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Israel
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Tell Abib
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Israel
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Yerushalayim
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Israel
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Ramat gan
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Italy
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Torino
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Italy
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Napoli
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Italy
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Pordenone
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Japan
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Aichi
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Japan
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Ehime
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Japan
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Fukuoka
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Japan
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Hokkaido
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Japan
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Hyogo
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tokyo
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Japan
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Chiba
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Japan
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Okayama
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul-teukbyeolsi [Seoul]
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Netherlands
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Groningen
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New Zealand
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Canterbury
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New Zealand
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Wellington
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Norway
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Vestfold
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Norway
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Oslo
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Puerto Rico
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San Juan
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Russian Federation
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Moskva
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Spain
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Barcelona [Barcelona]
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Spain
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Madrid
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Spain
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Valenciana, Comunitat
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Spain
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Zaragoza
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Sweden
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Stockholms Lan [se-01]
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Sweden
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Uppsala Lan [se-03]
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Sweden
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Vasterbottens Lan [se-24]
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Switzerland
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Zurich
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Taiwan
State/province [86] 0 0
Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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United Kingdom
State/province [89] 0 0
Edinburgh, City Of
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United Kingdom
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Glasgow City
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United Kingdom
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London, City Of
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United Kingdom
State/province [92] 0 0
Broomfield

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab
(MK-3475) in participants from previous Merck pembrolizumab-based parent studies who
roll-over into this extension study.

This study will consist of three phases: 1) First Course Phase, 2) Survival Follow-up Phase
or 3) Second Course Phase. Each participant will roll-over to this extension study in one of
the following three phases, depending on the study phase they were in at the completion of
the parent study. Participants who were in the First Course Phase of study treatment in their
parent study will enter the First Course Phase of this study and complete up to 35 cycles of
study treatment with pembrolizumab or a pembrolizumab-based combination. Participants who
were in the Follow-up Phase in the parent study (post-treatment or Survival Follow-up Phase)
will enter the Survival Follow-up Phase of this study. Participants who were in the Second
Course Phase in their parent study will enter Second Course Phase of this study and complete
up to 17 cycles of study treatment with pembrolizumab or a pembrolizumab-based combination.

Any participant originating from a parent trial where crossover to pembrolizumab was
permitted upon disease progression may be eligible for 35 doses (approximately 2 years) of
pembrolizumab, if they progress while on the control arm and pembrolizumab is approved for
the indication in the country where the potential eligible crossover participant is being
evaluated.
Trial website
https://clinicaltrials.gov/show/NCT03486873
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/NCT03486873