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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03884101




Registration number
NCT03884101
Ethics application status
Date submitted
19/03/2019
Date registered
21/03/2019
Date last updated
2/07/2020

Titles & IDs
Public title
Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001)
Scientific title
A Phase 3 Randomized, Open-Label, Study of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for First-line Treatment of Advanced or Recurrent Endometrial Carcinoma (LEAP-001)
Secondary ID [1] 0 0
2018-003009-24
Secondary ID [2] 0 0
7902-001
Universal Trial Number (UTN)
Trial acronym
LEAP-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib
Other interventions - Pembrolizumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Carboplatin

Experimental: Lenvatinib + Pembrolizumab - Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.

Active Comparator: Paclitaxel + Carboplatin - Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle.


Treatment: Drugs: Lenvatinib
Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.

Other interventions: Pembrolizumab
Pembrolizumab 200 mg IV infusion given on Day 1 of each cycle.

Treatment: Drugs: Paclitaxel
Paclitaxel 175 mg/m^2 IV infusion given on Day 1 of each cycle.

Treatment: Drugs: Carboplatin
Carboplatin 10 mg/mL IV infusion at a total dose of are-under-the-curve (AUC) 6 (per Calvert's formula) given on Day 1 of each cycle.

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

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) - Progression-free survival based on RECIST 1.1 as assessed by BICR. Progression-free survival is measured from the time of randomization to the first documented disease progression or death due to any cause, whichever occurs first.
Timepoint [1] 0 0
Up to approximately 31 months
Primary outcome [2] 0 0
Overall Survival (OS) - Overall survival is measured from the time of randomization up to death due to any cause.
Timepoint [2] 0 0
Up to approximately 45 months
Secondary outcome [1] 0 0
Objective response rate (ORR ) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent review (BICR) - The ORR (either confirmed complete response [CR] or partial response [PR]) based on RECIST 1.1 and assessed by BICR will be determined in mismatch repair proficient (pMMR) participants and in all-comer participants who have measurable disease at study entry.
Timepoint [1] 0 0
Up to approximately 31 months
Secondary outcome [2] 0 0
Change from baseline in the global score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) in pMMR and in all-comer participants - The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer. It contains 30 questions (items), 24 of which aggregate into nine multi-item scales representing various aspects, or dimensions, of quality of life (QoL): one global scale, five functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea, pain), and six additional single-symptom items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Individual items are scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation; a higher score on the global and functional scales represents a higher ("better") level of functioning, and a higher score on the symptom scale represents a higher ("worse") level of symptoms.
Timepoint [2] 0 0
Baseline and designated time points up to 27 months
Secondary outcome [3] 0 0
Percentage of participants experiencing an adverse event (AE) - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Timepoint [3] 0 0
Up to approximately 27 months (through 90 days after the last dose of study treatment)
Secondary outcome [4] 0 0
Percentage of participants experiencing a serious adverse event (SAE) - An SAE is an AE that results in death, is life-threatening, requires or prolongs hospitalization, results in persistent or significant disability, is a congenital birth defect, or is another important medical event.
Timepoint [4] 0 0
Up to approximately 28 months (through 120 days after the last dose of study treatment)
Secondary outcome [5] 0 0
Percentage of participants experiencing an immune-related AE (irAE) - Immune-related AEs will be monitored in both arms.
Timepoint [5] 0 0
Up to approximately 27 months (through 90 days after the last dose of study treatment)
Secondary outcome [6] 0 0
Percentage of participants discontinuing from study treatment due to an AE(s) - Discontinuations related to AEs will be monitored in both arms.
Timepoint [6] 0 0
Up to approximately 24 months (through the last dose of study treatment)

Eligibility
Key inclusion criteria
- Has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma
with disease that is either measurable or non-measurable but radiographically
apparent, per RECIST 1.1 as assessed by BICR (note: may have received prior
chemotherapy only if administered concurrently with radiation; may have received prior
radiation without concurrent chemotherapy; may have received prior hormonal therapy
for treatment of endometrial carcinoma, provided that it was discontinued =1 week
prior to randomization; and may have received 1 prior line of systemic platinum-based
adjuvant and/or neoadjuvant chemotherapy)

- Has provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion that was not previously irradiated, for determination of mismatch
repair (MMR) status

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as
assessed within 7 days prior to the first dose of study intervention

- Is not pregnant or breastfeeding, and is either not a woman of childbearing potential
(WOCBP) or is a WOCBP who agrees to use contraception during the study and for =120
days after pembrolizumab, =30 days after lenvatinib, or =196 days after (chemotherapy)
[if a WOCBP, a pregnancy test will be required within 24 hours of first dose of study
drug]

- Has adequately controlled blood pressure within 7 days prior to randomization

- Has adequate organ function based on assessment within 7 days prior to the first dose
of study intervention
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma or
other high grade sarcomas, or endometrial stromal sarcomas

- Has a central nervous system (CNS) metastasis, unless local therapy (e.g., whole brain
radiation therapy, surgery, or radiosurgery) has been completed and have discontinued
use of corticosteroids for this indication for =4 weeks prior to starting study
medication (major surgery within 3 weeks of the first dose of study drug will be
exclusionary)

- Has a known additional malignancy (other than endometrial carcinoma) that is
progressing or has required active treatment in the last 3 years

- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that might affect the absorption of lenvatinib

- Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula

- Has radiographic evidence of major blood vessel invasion/infiltration

- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to
randomization

- Has significant cardiovascular impairment within 12 months of the first dose of study
intervention such as history of congestive heart failure greater than New York Heart
Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular
accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability

- Has any infection requiring systemic treatment

- Has not recovered adequately from any toxicity and/or complications from major surgery
prior to randomization

- Has a known history of human immunodeficiency virus (HIV) infection (HIV test is
required at screening)

- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (Hepatitis B and C testing is required at
screening)

- Has a history of (non-infectious) pneumonitis that required treatment with steroids,
or has current pneumonitis

- Has a known history of active tuberculosis (tuberculosis test is required at
screening)

- 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
cooperation with the requirements of the study

- 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 randomization

- Has an active autoimmune disease (with the exception of psoriasis) that has required
systemic treatment in the past 2 years (i.e., with use of disease modifying agents,
corticosteroids or immunosuppressive drugs)

- Has received prior systemic chemotherapy in any setting for the treatment of
endometrial carcinoma (note: prior chemotherapy administered concurrently with
radiation is permitted)

- Has received prior radiotherapy within 4 weeks prior to randomization (participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis - a 2-week washout is
permitted for palliative radiation to non-CNS disease and vaginal brachytherapy)

- Has received prior hormonal therapy for the treatment of endometrial carcinoma within
1 week of randomization

- Has received prior therapy with any treatment targeting vascular endothelial growth
factor (VEGF)-directed angiogenesis, an anti-programmed cell death (PD)-1, anti-PD
ligand (L)1, or anti-PD L2 agent, or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)

- Has received a live vaccine within 30 days prior to the first dose of study
intervention

- Has known intolerance to study intervention (or any of the excipients)

- Has had an allogenic tissue/solid organ transplant

- 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 randomization

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
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,VIC,WA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 1605) - Camperdown
Recruitment hospital [2] 0 0
Prince of Wales Hospital [Australia] ( Site 1603) - Randwick
Recruitment hospital [3] 0 0
Royal North Shore Hospital ( Site 1600) - St Leonards
Recruitment hospital [4] 0 0
The Crown Princess Mary Cancer Centre Westmead ( Site 1602) - Westmead
Recruitment hospital [5] 0 0
Monash Health ( Site 1606) - Clayton
Recruitment hospital [6] 0 0
Epworth Freemasons Hospital ( Site 1609) - Melbourne
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital ( Site 1604) - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3002 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maine
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
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New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
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United States of America
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North Carolina
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United States of America
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North Dakota
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United States of America
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Oregon
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United States of America
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South Dakota
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
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Argentina
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Buenos Aires
Country [20] 0 0
Argentina
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La Rioja
Country [21] 0 0
Austria
State/province [21] 0 0
Steiermark
Country [22] 0 0
Austria
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Tirol
Country [23] 0 0
Austria
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Wien
Country [24] 0 0
Belgium
State/province [24] 0 0
Bruxelles-Capitale, Region De
Country [25] 0 0
Belgium
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Oost-Vlaanderen
Country [26] 0 0
Belgium
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Vlaams-Brabant
Country [27] 0 0
Belgium
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West-Vlaanderen
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Brazil
State/province [28] 0 0
Ceara
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Brazil
State/province [29] 0 0
Goias
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Brazil
State/province [30] 0 0
Rio Grande Do Sul
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Brazil
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Sao Paulo
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Brazil
State/province [32] 0 0
Rio de Janeiro
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Canada
State/province [33] 0 0
Alberta
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Canada
State/province [34] 0 0
British Columbia
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Canada
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Ontario
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Canada
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Quebec
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China
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Anhui
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China
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Beijing
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China
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Chongqing
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China
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Guangdong
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China
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Hubei
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China
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Hunan
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China
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Jiangsu
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China
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Shaanxi
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China
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Shanghai
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China
State/province [46] 0 0
Xinjiang
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China
State/province [47] 0 0
Zhejiang
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Germany
State/province [48] 0 0
Nordrhein-Westfalen
Country [49] 0 0
Germany
State/province [49] 0 0
Thuringen
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Israel
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HaMerkaz
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Israel
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Heifa
Country [52] 0 0
Israel
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Tell Abib
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Italy
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Forli-Cesena
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Italy
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Roma
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Italy
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Venezia
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Italy
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Arezzo
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Italy
State/province [57] 0 0
Bari
Country [58] 0 0
Italy
State/province [58] 0 0
Bologna
Country [59] 0 0
Italy
State/province [59] 0 0
Brindisi
Country [60] 0 0
Italy
State/province [60] 0 0
Catania
Country [61] 0 0
Italy
State/province [61] 0 0
Napoli
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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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Gunma
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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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Kanagawa
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Japan
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Okinawa
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Japan
State/province [69] 0 0
Saitama
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Japan
State/province [70] 0 0
Tokyo
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Japan
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Niigata
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Japan
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Osaka
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Korea, Republic of
State/province [73] 0 0
Kyonggi-do
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Seoul-teukbyeolsi [Seoul]
Country [75] 0 0
Mexico
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Chiapas
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Mexico
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Nuevo Leon
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Mexico
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Chihuahua
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Mexico
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Ciudad de Mexico
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Mexico
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Mexico City
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Poland
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Lubelskie
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Poland
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Mazowieckie
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Poland
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Podlaskie
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Poland
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Slaskie
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Poland
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Wielkopolskie
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Russian Federation
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Krasnoyarskiy Kray
Country [86] 0 0
Russian Federation
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Moskva
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Russian Federation
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Samarskaya Oblast'
Country [88] 0 0
Russian Federation
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Sankt-Peterburg
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Russian Federation
State/province [89] 0 0
Tatarstan, Respublika
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Russian Federation
State/province [90] 0 0
Tomskaya Oblast'
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Spain
State/province [91] 0 0
A Coruna [La Coruna]
Country [92] 0 0
Spain
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Barcelona [Barcelona]
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Spain
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Valenciana, Comunitat
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Spain
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Cordoba
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Spain
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Madrid
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Spain
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Malaga
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Taiwan
State/province [97] 0 0
Taichung
Country [98] 0 0
Taiwan
State/province [98] 0 0
Taipei
Country [99] 0 0
Taiwan
State/province [99] 0 0
Taoyuan
Country [100] 0 0
Turkey
State/province [100] 0 0
Adana
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Turkey
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Ankara
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Turkey
State/province [102] 0 0
Antalya
Country [103] 0 0
Turkey
State/province [103] 0 0
Bursa
Country [104] 0 0
Ukraine
State/province [104] 0 0
Dnipropetrovska Oblast
Country [105] 0 0
Ukraine
State/province [105] 0 0
Ivano-Frankivska Oblast
Country [106] 0 0
Ukraine
State/province [106] 0 0
Kharkivska Oblast
Country [107] 0 0
Ukraine
State/province [107] 0 0
Khmelnytska Oblast
Country [108] 0 0
Ukraine
State/province [108] 0 0
Kyivska Oblast
Country [109] 0 0
Ukraine
State/province [109] 0 0
Odeska Oblast
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Edinburgh, City Of
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Oxfordshire
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United Kingdom
State/province [112] 0 0
Newcastle Upon Tyne
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Northwood

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 compare the efficacy of pembrolizumab + lenvatinib to
chemotherapy in female participants with Stage III, IV, or recurrent endometrial carcinoma.
It is hypothesized that the combination of pembrolizumab + lenvatinib will be superior to
chemotherapy for progression-free survival (PFS) per Response Evaluation Criteria In Solid
Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR). It is also
hypothesized that the combination of pembrolizumab + lenvatinib will be superior to
chemotherapy for overall survival (OS).
Trial website
https://clinicaltrials.gov/show/NCT03884101
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/NCT03884101