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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03486873
Ethics application status
Date submitted
29/03/2018
Date registered
3/04/2018
Date last updated
11/06/2024

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 3 Study to Evaluate the Long-term Safety and Efficacy in Participants Who Are Currently on Treatment or in Follow-up in Studies That Include Pembrolizumab
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
Hematologic Malignancies 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

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

Experimental: Pembrolizumab 200 mg - 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 400 mg - Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 17 administrations or more for First Course participants and up to 8 administrations for Second Course participants.

Experimental: Pembrolizumab 200 mg + 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.

Experimental: Pembrolizumab 400 mg + SOC (Per Parent Study) - Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle PLUS SOC treatment (or per parent study if there is no SOC) for up to 17 administrations or more for First Course participants and up to 8 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 dose matched non-pembrolizumab SOC treatment (e.g. chemotherapy) they were receiving as per parent study protocol.

Experimental: Lenvatinib 20 mg - Participants with body weight (BW)\>60kg receive Lenvatinib 20mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Experimental: Lenvatinib 24 mg - Participants with body weight (BW)\>60 kg receive Lenvatinib 24 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Experimental: Lenvatinib 12 mg - Participants with body weight (BW)\>60 kg receive Lenvatinib 12 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Experimental: Lenvatinib 8 mg - Participants with body weight (BW)\<60 kg receive Lenvatinib 8 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.


Treatment: Drugs: Pembrolizumab
200 or 400 mg IV infusion

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

Treatment: Drugs: Lenvatinib
Oral capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
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
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
Timepoint [2] 0 0
Up to approximately 10 years
Secondary outcome [3] 0 0
Number of Participants Who Experience Serious Adverse Events (SAEs)
Timepoint [3] 0 0
Up to approximately 42 months (Up to 90 days after last dose of study treatment)
Secondary outcome [4] 0 0
Number of Participants Who Experience Adverse Events of Special Interest (AEOSI)
Timepoint [4] 0 0
Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary outcome [5] 0 0
Number of Participants Who Experience Clinically Significant Adverse Events (CSAE)
Timepoint [5] 0 0
Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary outcome [6] 0 0
Number of Participants Who Experience Events of Clinical Interest (ECI)
Timepoint [6] 0 0
Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary outcome [7] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [7] 0 0
Up to approximately 39 months

Eligibility
Key inclusion criteria
* Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready.
* Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase.

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.
* 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.

Additional eligibility criteria for participants who enter dosing with Lenvatinib:

* Adequately controlled blood pressure (BP) to <150/90 mmHg, with or without antihypertensive medications.
* For male agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for 7 days after the last dose of lenvatinib.
* Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for =4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) or is a WOCBP who is abstinent from heterosexual intercourse.
Minimum age
18 Years
Maximum age
No limit
Sex
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.
* Non-small cell lung cancer (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. For parent studies where inclusion of participants with hepatitis was permitted, MK-3475-587 will follow the parent study eligibility criteria for hepatitis.
* 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).

Additional exclusion criteria for participants who enter dosing with Lenvatinib:

* Has had major surgery within 3 weeks prior to first dose of study intervention(s).
* Has preexisting =Grade 3 gastrointestinal or non-gastrointestinal fistula.
* Has urine protein =1 g/24 hours.
* Has LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
* Prolongation of QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval to >480 ms.
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
* Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
* Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
* Has a history of any contraindication or has a severe hypersensitivity to any components of lenvatinib.

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
21/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/08/2043
Actual
Sample size
Target
3500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 3003) - Camperdown
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital-A.W. Morrow Gastroenterology and Liver Centre ( Site 3016) - Camperdown
Recruitment hospital [3] 0 0
Liverpool Hospital-Medical Oncology ( Site 3021) - Liverpool
Recruitment hospital [4] 0 0
Macquarie University ( Site 3010) - Macquarie University
Recruitment hospital [5] 0 0
Mater Hospital Sydney ( Site 3007) - North Sydney
Recruitment hospital [6] 0 0
Orange Hospital-Clinical Trials Unit ( Site 3027) - Orange
Recruitment hospital [7] 0 0
Port Macquarie - Mid North Coast Cancer Institute-Medical Oncology ( Site 3020) - Port Macquarie
Recruitment hospital [8] 0 0
Royal North Shore Hospital-Medical Oncology Clinical Trials ( Site 3025) - St Leonards
Recruitment hospital [9] 0 0
Calvary Mater Newcastle ( Site 3005) - Waratah
Recruitment hospital [10] 0 0
Westmead Hospital ( Site 3000) - Westmead
Recruitment hospital [11] 0 0
Melanoma Institute Australia ( Site 3001) - Wollstonecraft
Recruitment hospital [12] 0 0
Mater Misericordiae Limited-Medical Oncology ( Site 3019) - Brisbane
Recruitment hospital [13] 0 0
Gallipoli Medical Research Ltd ( Site 3011) - Brisbane
Recruitment hospital [14] 0 0
Royal Brisbane and Women s Hospital ( Site 3009) - Herston
Recruitment hospital [15] 0 0
Tasman Oncology Research Pty Ltd ( Site 3012) - Southport
Recruitment hospital [16] 0 0
The Townsville Hospital ( Site 3017) - Townsville
Recruitment hospital [17] 0 0
Princess Alexandra Hospital ( Site 3002) - Woolloongabba
Recruitment hospital [18] 0 0
Royal Adelaide Hospital ( Site 3014) - Adelaide
Recruitment hospital [19] 0 0
The Queen Elizabeth Hospital ( Site 3026) - Woodville
Recruitment hospital [20] 0 0
Monash Health ( Site 3015) - Clayton
Recruitment hospital [21] 0 0
Austin Health-Austin Hospital ( Site 3004) - Heidelberg
Recruitment hospital [22] 0 0
Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 3008) - Melbourne
Recruitment hospital [23] 0 0
St Vincent's Hospital-Oncology Clinical Trials ( Site 3018) - Melbourne
Recruitment hospital [24] 0 0
Western Health-Sunshine & Footscray Hospitals ( Site 3023) - St Albans
Recruitment hospital [25] 0 0
Ballarat Oncology & Haematology Services ( Site 3022) - Wendouree
Recruitment hospital [26] 0 0
Sir Charles Gairdner Hospital ( Site 3006) - Nedlands
Recruitment hospital [27] 0 0
St John of God Subiaco Hospital ( Site 3013) - Subiaco
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2109 - Macquarie University
Recruitment postcode(s) [4] 0 0
2060 - North Sydney
Recruitment postcode(s) [5] 0 0
2800 - Orange
Recruitment postcode(s) [6] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [7] 0 0
2065 - St Leonards
Recruitment postcode(s) [8] 0 0
2298 - Waratah
Recruitment postcode(s) [9] 0 0
2145 - Westmead
Recruitment postcode(s) [10] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [11] 0 0
4101 - Brisbane
Recruitment postcode(s) [12] 0 0
4120 - Brisbane
Recruitment postcode(s) [13] 0 0
4029 - Herston
Recruitment postcode(s) [14] 0 0
4215 - Southport
Recruitment postcode(s) [15] 0 0
4814 - Townsville
Recruitment postcode(s) [16] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [17] 0 0
5000 - Adelaide
Recruitment postcode(s) [18] 0 0
5011 - Woodville
Recruitment postcode(s) [19] 0 0
3168 - Clayton
Recruitment postcode(s) [20] 0 0
3084 - Heidelberg
Recruitment postcode(s) [21] 0 0
3000 - Melbourne
Recruitment postcode(s) [22] 0 0
3065 - Melbourne
Recruitment postcode(s) [23] 0 0
3021 - St Albans
Recruitment postcode(s) [24] 0 0
3355 - Wendouree
Recruitment postcode(s) [25] 0 0
6009 - Nedlands
Recruitment postcode(s) [26] 0 0
6008 - Subiaco
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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District of Columbia
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Florida
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Georgia
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Hawaii
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Illinois
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Iowa
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United States of America
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Kentucky
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Nevada
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United States of America
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New Jersey
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United States of America
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New York
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North Carolina
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North Dakota
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Ohio
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United States of America
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Oklahoma
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Oregon
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Pennsylvania
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South Dakota
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Tennessee
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Texas
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United States of America
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Virginia
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United States of America
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Washington
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Argentina
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Buenos Aires
Country [31] 0 0
Argentina
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Caba
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Argentina
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Rio Negro
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Argentina
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Santa Fe
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Argentina
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Cordoba
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Argentina
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La Rioja
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Argentina
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Tucuman
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Austria
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Oberosterreich
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Austria
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Steiermark
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Austria
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Tirol
Country [40] 0 0
Austria
State/province [40] 0 0
Salzburg
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Austria
State/province [41] 0 0
Wien
Country [42] 0 0
Belgium
State/province [42] 0 0
Antwerpen
Country [43] 0 0
Belgium
State/province [43] 0 0
Bruxelles-Capitale, Region De
Country [44] 0 0
Belgium
State/province [44] 0 0
Namur
Country [45] 0 0
Belgium
State/province [45] 0 0
Oost-Vlaanderen
Country [46] 0 0
Belgium
State/province [46] 0 0
Vlaams-Brabant
Country [47] 0 0
Brazil
State/province [47] 0 0
Ceara
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Brazil
State/province [48] 0 0
Rio Grande Do Sul
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Brazil
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Santa Catarina
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Brazil
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Sao Paulo
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Brazil
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Rio de Janeiro
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Canada
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Alberta
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Canada
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Ontario
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Canada
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Quebec
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Chile
State/province [55] 0 0
Araucania
Country [56] 0 0
Chile
State/province [56] 0 0
Region M. De Santiago
Country [57] 0 0
Chile
State/province [57] 0 0
Valparaiso
Country [58] 0 0
China
State/province [58] 0 0
Anhui
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China
State/province [59] 0 0
Beijing
Country [60] 0 0
China
State/province [60] 0 0
Chongqing
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China
State/province [61] 0 0
Fujian
Country [62] 0 0
China
State/province [62] 0 0
Guangdong
Country [63] 0 0
China
State/province [63] 0 0
Heilongjiang
Country [64] 0 0
China
State/province [64] 0 0
Hubei
Country [65] 0 0
China
State/province [65] 0 0
Hunan
Country [66] 0 0
China
State/province [66] 0 0
Jiangsu
Country [67] 0 0
China
State/province [67] 0 0
Jilin
Country [68] 0 0
China
State/province [68] 0 0
Shaanxi
Country [69] 0 0
China
State/province [69] 0 0
Shanghai
Country [70] 0 0
China
State/province [70] 0 0
Sichuan
Country [71] 0 0
China
State/province [71] 0 0
Tianjin
Country [72] 0 0
China
State/province [72] 0 0
Zhejiang
Country [73] 0 0
Colombia
State/province [73] 0 0
Antioquia
Country [74] 0 0
Colombia
State/province [74] 0 0
Cordoba
Country [75] 0 0
Colombia
State/province [75] 0 0
Distrito Capital De Bogota
Country [76] 0 0
Colombia
State/province [76] 0 0
Valle Del Cauca
Country [77] 0 0
Czechia
State/province [77] 0 0
Brno-mesto
Country [78] 0 0
Czechia
State/province [78] 0 0
Olomoucky Kraj
Country [79] 0 0
Czechia
State/province [79] 0 0
Praha 4
Country [80] 0 0
Czechia
State/province [80] 0 0
Praha 5
Country [81] 0 0
Czechia
State/province [81] 0 0
Olomouc
Country [82] 0 0
Denmark
State/province [82] 0 0
Syddanmark
Country [83] 0 0
Estonia
State/province [83] 0 0
Tartumaa
Country [84] 0 0
Finland
State/province [84] 0 0
Pirkanmaa
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Finland
State/province [85] 0 0
Varsinais-Suomi
Country [86] 0 0
France
State/province [86] 0 0
Alpes-Maritimes
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France
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Alsace
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France
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Aquitaine
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France
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Auvergne
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France
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Bouches-du-Rhone
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France
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Cote-d Or
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France
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Doubs
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France
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Finistere
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France
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Gironde
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France
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Haute-Garonne
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France
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Hauts-de-Seine
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France
State/province [97] 0 0
Ile-de-France
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France
State/province [98] 0 0
Ille-et-Vilaine
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France
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Indre-et-Loire
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France
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Loire-Atlantique
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France
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Lorraine
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France
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Nord
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France
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Puy-de-Dome
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France
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Rhone-Alpes
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France
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Rhone
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France
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Sarthe
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France
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Seine-Saint-Denis
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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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Hessen
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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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Saarland
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Germany
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Sachsen
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Germany
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Schleswig-Holstein
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Germany
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Thuringen
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Germany
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Berlin
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Germany
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Hamburg
Country [121] 0 0
Greece
State/province [121] 0 0
Attiki
Country [122] 0 0
Guatemala
State/province [122] 0 0
Guatemala
Country [123] 0 0
Hong Kong
State/province [123] 0 0
Hksar
Country [124] 0 0
Hungary
State/province [124] 0 0
Bekes
Country [125] 0 0
Hungary
State/province [125] 0 0
Borsod-Abauj-Zemplen
Country [126] 0 0
Hungary
State/province [126] 0 0
Fejer
Country [127] 0 0
Hungary
State/province [127] 0 0
Jasz-Nagykun-Szolnok
Country [128] 0 0
Hungary
State/province [128] 0 0
Pest
Country [129] 0 0
Hungary
State/province [129] 0 0
Vas
Country [130] 0 0
Hungary
State/province [130] 0 0
Veszprem
Country [131] 0 0
Hungary
State/province [131] 0 0
Budapest
Country [132] 0 0
Hungary
State/province [132] 0 0
Debrecen
Country [133] 0 0
Hungary
State/province [133] 0 0
Kaposvar
Country [134] 0 0
Hungary
State/province [134] 0 0
Zalaegerszeg
Country [135] 0 0
Ireland
State/province [135] 0 0
Leinster
Country [136] 0 0
Ireland
State/province [136] 0 0
Dublin
Country [137] 0 0
Israel
State/province [137] 0 0
Haifa
Country [138] 0 0
Israel
State/province [138] 0 0
Jerusalem
Country [139] 0 0
Israel
State/province [139] 0 0
Petah-Tikva
Country [140] 0 0
Israel
State/province [140] 0 0
Ramat Gan
Country [141] 0 0
Israel
State/province [141] 0 0
Tel Aviv
Country [142] 0 0
Israel
State/province [142] 0 0
Zerifin
Country [143] 0 0
Italy
State/province [143] 0 0
Lazio
Country [144] 0 0
Italy
State/province [144] 0 0
Milano
Country [145] 0 0
Italy
State/province [145] 0 0
Piemonte
Country [146] 0 0
Italy
State/province [146] 0 0
Pordenone
Country [147] 0 0
Italy
State/province [147] 0 0
Torino
Country [148] 0 0
Italy
State/province [148] 0 0
Umbria
Country [149] 0 0
Italy
State/province [149] 0 0
Bergamo
Country [150] 0 0
Italy
State/province [150] 0 0
Brescia
Country [151] 0 0
Italy
State/province [151] 0 0
Genova
Country [152] 0 0
Italy
State/province [152] 0 0
Napoli
Country [153] 0 0
Italy
State/province [153] 0 0
Parma
Country [154] 0 0
Italy
State/province [154] 0 0
Roma
Country [155] 0 0
Italy
State/province [155] 0 0
Siena
Country [156] 0 0
Italy
State/province [156] 0 0
Terni
Country [157] 0 0
Japan
State/province [157] 0 0
Aichi
Country [158] 0 0
Japan
State/province [158] 0 0
Chiba
Country [159] 0 0
Japan
State/province [159] 0 0
Ehime
Country [160] 0 0
Japan
State/province [160] 0 0
Fukuoka
Country [161] 0 0
Japan
State/province [161] 0 0
Hokkaido
Country [162] 0 0
Japan
State/province [162] 0 0
Hyogo
Country [163] 0 0
Japan
State/province [163] 0 0
Ishikawa
Country [164] 0 0
Japan
State/province [164] 0 0
Kagawa
Country [165] 0 0
Japan
State/province [165] 0 0
Kanagawa
Country [166] 0 0
Japan
State/province [166] 0 0
Miyagi
Country [167] 0 0
Japan
State/province [167] 0 0
Nara
Country [168] 0 0
Japan
State/province [168] 0 0
Okayama
Country [169] 0 0
Japan
State/province [169] 0 0
Okinawa
Country [170] 0 0
Japan
State/province [170] 0 0
Osaka
Country [171] 0 0
Japan
State/province [171] 0 0
Saitama
Country [172] 0 0
Japan
State/province [172] 0 0
Shizuoka
Country [173] 0 0
Japan
State/province [173] 0 0
Tochigi
Country [174] 0 0
Japan
State/province [174] 0 0
Tokyo
Country [175] 0 0
Japan
State/province [175] 0 0
Yamaguchi
Country [176] 0 0
Japan
State/province [176] 0 0
Gifu
Country [177] 0 0
Japan
State/province [177] 0 0
Hiroshima
Country [178] 0 0
Japan
State/province [178] 0 0
Kochi
Country [179] 0 0
Japan
State/province [179] 0 0
Wakayama
Country [180] 0 0
Korea, Republic of
State/province [180] 0 0
Jeonranamdo
Country [181] 0 0
Korea, Republic of
State/province [181] 0 0
Kyonggi-do
Country [182] 0 0
Korea, Republic of
State/province [182] 0 0
Seoul
Country [183] 0 0
Korea, Republic of
State/province [183] 0 0
Taegu-Kwangyokshi
Country [184] 0 0
Korea, Republic of
State/province [184] 0 0
Taejon-Kwangyokshi
Country [185] 0 0
Latvia
State/province [185] 0 0
Liepaja
Country [186] 0 0
Latvia
State/province [186] 0 0
Riga
Country [187] 0 0
Lithuania
State/province [187] 0 0
Klaipedos Miestas
Country [188] 0 0
Lithuania
State/province [188] 0 0
Vilniaus Miestas
Country [189] 0 0
Lithuania
State/province [189] 0 0
Vilnius
Country [190] 0 0
Malaysia
State/province [190] 0 0
Pahang
Country [191] 0 0
Malaysia
State/province [191] 0 0
Pulau Pinang
Country [192] 0 0
Malaysia
State/province [192] 0 0
Kuala Lumpur
Country [193] 0 0
Mexico
State/province [193] 0 0
Distrito Federal
Country [194] 0 0
Mexico
State/province [194] 0 0
Nuevo Leon
Country [195] 0 0
Mexico
State/province [195] 0 0
Oaxaca
Country [196] 0 0
Mexico
State/province [196] 0 0
Yucatan
Country [197] 0 0
Mexico
State/province [197] 0 0
Cdmx
Country [198] 0 0
Netherlands
State/province [198] 0 0
Gelderland
Country [199] 0 0
Netherlands
State/province [199] 0 0
Noord-Holland
Country [200] 0 0
Netherlands
State/province [200] 0 0
Zuid-Holland
Country [201] 0 0
Netherlands
State/province [201] 0 0
Groningen
Country [202] 0 0
New Zealand
State/province [202] 0 0
Canterbury
Country [203] 0 0
New Zealand
State/province [203] 0 0
Waikato
Country [204] 0 0
New Zealand
State/province [204] 0 0
Auckland
Country [205] 0 0
New Zealand
State/province [205] 0 0
Wellington
Country [206] 0 0
Norway
State/province [206] 0 0
Vestfold
Country [207] 0 0
Norway
State/province [207] 0 0
Oslo
Country [208] 0 0
Peru
State/province [208] 0 0
Lima
Country [209] 0 0
Philippines
State/province [209] 0 0
National Capital Region
Country [210] 0 0
Poland
State/province [210] 0 0
Kujawsko-pomorskie
Country [211] 0 0
Poland
State/province [211] 0 0
Lodzkie
Country [212] 0 0
Poland
State/province [212] 0 0
Malopolskie
Country [213] 0 0
Poland
State/province [213] 0 0
Mazowieckie
Country [214] 0 0
Poland
State/province [214] 0 0
Opolskie
Country [215] 0 0
Poland
State/province [215] 0 0
Podlaskie
Country [216] 0 0
Poland
State/province [216] 0 0
Wielkopolskie
Country [217] 0 0
Poland
State/province [217] 0 0
Zachodniopomorskie
Country [218] 0 0
Portugal
State/province [218] 0 0
Lisboa
Country [219] 0 0
Portugal
State/province [219] 0 0
Porto
Country [220] 0 0
Puerto Rico
State/province [220] 0 0
Ponce
Country [221] 0 0
Puerto Rico
State/province [221] 0 0
San Juan
Country [222] 0 0
Romania
State/province [222] 0 0
Suceava
Country [223] 0 0
Russian Federation
State/province [223] 0 0
Baskortostan, Respublika
Country [224] 0 0
Russian Federation
State/province [224] 0 0
Belgorodskaya Oblast
Country [225] 0 0
Russian Federation
State/province [225] 0 0
Ivanovskaya Oblast
Country [226] 0 0
Russian Federation
State/province [226] 0 0
Leningradskaya Oblast
Country [227] 0 0
Russian Federation
State/province [227] 0 0
Mordoviya, Respublika
Country [228] 0 0
Russian Federation
State/province [228] 0 0
Moskva
Country [229] 0 0
Russian Federation
State/province [229] 0 0
Sankt-Peterburg
Country [230] 0 0
Russian Federation
State/province [230] 0 0
Stavropol Skiy Kray
Country [231] 0 0
Russian Federation
State/province [231] 0 0
Tatarstan, Respublika
Country [232] 0 0
Russian Federation
State/province [232] 0 0
Tomskaya Oblast
Country [233] 0 0
Russian Federation
State/province [233] 0 0
Tyumenskaya Oblast
Country [234] 0 0
Russian Federation
State/province [234] 0 0
Udmurtskaya Respublika
Country [235] 0 0
Singapore
State/province [235] 0 0
Central Singapore
Country [236] 0 0
Singapore
State/province [236] 0 0
South West
Country [237] 0 0
South Africa
State/province [237] 0 0
Gauteng
Country [238] 0 0
South Africa
State/province [238] 0 0
Limpopo
Country [239] 0 0
South Africa
State/province [239] 0 0
Western Cape
Country [240] 0 0
Spain
State/province [240] 0 0
Andalucia
Country [241] 0 0
Spain
State/province [241] 0 0
Asturias
Country [242] 0 0
Spain
State/province [242] 0 0
Baleares
Country [243] 0 0
Spain
State/province [243] 0 0
Barcelona
Country [244] 0 0
Spain
State/province [244] 0 0
Cantabria
Country [245] 0 0
Spain
State/province [245] 0 0
Cataluna
Country [246] 0 0
Spain
State/province [246] 0 0
La Coruna
Country [247] 0 0
Spain
State/province [247] 0 0
Las Palmas
Country [248] 0 0
Spain
State/province [248] 0 0
Madrid, Comunidad De
Country [249] 0 0
Spain
State/province [249] 0 0
Madrid
Country [250] 0 0
Spain
State/province [250] 0 0
Malaga
Country [251] 0 0
Spain
State/province [251] 0 0
Tarragona
Country [252] 0 0
Spain
State/province [252] 0 0
Valenciana, Comunitat
Country [253] 0 0
Spain
State/province [253] 0 0
Valencia
Country [254] 0 0
Spain
State/province [254] 0 0
Alicante
Country [255] 0 0
Spain
State/province [255] 0 0
Jaen
Country [256] 0 0
Spain
State/province [256] 0 0
Sevilla
Country [257] 0 0
Spain
State/province [257] 0 0
Zaragoza
Country [258] 0 0
Sweden
State/province [258] 0 0
Stockholms Lan
Country [259] 0 0
Sweden
State/province [259] 0 0
Uppsala Lan
Country [260] 0 0
Sweden
State/province [260] 0 0
Vasterbottens Lan
Country [261] 0 0
Sweden
State/province [261] 0 0
Vastra Gotalands Lan
Country [262] 0 0
Switzerland
State/province [262] 0 0
Basel-Stadt
Country [263] 0 0
Switzerland
State/province [263] 0 0
Geneve
Country [264] 0 0
Switzerland
State/province [264] 0 0
Zurich
Country [265] 0 0
Taiwan
State/province [265] 0 0
Kaohsiung
Country [266] 0 0
Taiwan
State/province [266] 0 0
Taichung
Country [267] 0 0
Taiwan
State/province [267] 0 0
Tainan
Country [268] 0 0
Taiwan
State/province [268] 0 0
Taipei
Country [269] 0 0
Taiwan
State/province [269] 0 0
Taoyuan
Country [270] 0 0
Thailand
State/province [270] 0 0
Krung Thep Maha Nakhon
Country [271] 0 0
Turkey
State/province [271] 0 0
Istanbul
Country [272] 0 0
Turkey
State/province [272] 0 0
Adana
Country [273] 0 0
Turkey
State/province [273] 0 0
Ankara
Country [274] 0 0
Turkey
State/province [274] 0 0
Antalya
Country [275] 0 0
Turkey
State/province [275] 0 0
Edirne
Country [276] 0 0
Turkey
State/province [276] 0 0
Izmir
Country [277] 0 0
Turkey
State/province [277] 0 0
Kocaeli
Country [278] 0 0
Turkey
State/province [278] 0 0
Malatya
Country [279] 0 0
Ukraine
State/province [279] 0 0
Dnipropetrovska Oblast
Country [280] 0 0
Ukraine
State/province [280] 0 0
Ivano-Frankivska Oblast
Country [281] 0 0
Ukraine
State/province [281] 0 0
Kharkivska Oblast
Country [282] 0 0
Ukraine
State/province [282] 0 0
Kirovohradska Oblast
Country [283] 0 0
Ukraine
State/province [283] 0 0
Kyivska Oblast
Country [284] 0 0
Ukraine
State/province [284] 0 0
Lvivska Oblast
Country [285] 0 0
Ukraine
State/province [285] 0 0
Odeska Oblast
Country [286] 0 0
Ukraine
State/province [286] 0 0
Sumska Oblast
Country [287] 0 0
Ukraine
State/province [287] 0 0
Vinnytska Oblast
Country [288] 0 0
Ukraine
State/province [288] 0 0
Zakarpatska Oblast
Country [289] 0 0
Ukraine
State/province [289] 0 0
Zaporizka Oblast
Country [290] 0 0
United Kingdom
State/province [290] 0 0
Aberdeen City
Country [291] 0 0
United Kingdom
State/province [291] 0 0
Edinburgh, City Of
Country [292] 0 0
United Kingdom
State/province [292] 0 0
England
Country [293] 0 0
United Kingdom
State/province [293] 0 0
Essex
Country [294] 0 0
United Kingdom
State/province [294] 0 0
Glasgow City
Country [295] 0 0
United Kingdom
State/province [295] 0 0
Lancashire
Country [296] 0 0
United Kingdom
State/province [296] 0 0
London, City Of
Country [297] 0 0
United Kingdom
State/province [297] 0 0
Northern Ireland
Country [298] 0 0
United Kingdom
State/province [298] 0 0
Nottinghamshire
Country [299] 0 0
United Kingdom
State/province [299] 0 0
Leeds
Country [300] 0 0
United Kingdom
State/province [300] 0 0
Sutton
Country [301] 0 0
United Kingdom
State/province [301] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
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 transition 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 transition 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 with pembrolizumab or lenvatinib in their parent study will enter the First Course Phase of this study and complete up to 35 doses or more every 3 weeks (Q3W) or 17 doses or more every 6 weeks (Q6W) of study treatment with pembrolizumab or a pembrolizumab-based combination or lenvatinib according to arm assignment. 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 doses Q3W or 8 doses Q6W of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment.

Any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be eligible for 35 doses as Q3W or 17 doses Q6W of pembrolizumab (approximately 2 years), 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/study/NCT03486873
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03486873