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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03884101




Registration number
NCT03884101
Ethics application status
Date submitted
19/03/2019
Date registered
21/03/2019
Date last updated
4/03/2024

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
MK-7902-001
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)
Timepoint [1] 0 0
Up to approximately 31 months
Primary outcome [2] 0 0
Overall Survival (OS)
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)
Timepoint [1] 0 0
Up to approximately 31 months
Secondary outcome [2] 0 0
Mean change from baseline in the global health status/quality of life 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
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)
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)
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)
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)
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 nonmeasurable 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 =180 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
Sex
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 or any other condition that might affect the
absorption of lenvatinib

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

- Has radiographic evidence of major blood vessel invasion/infiltration

- Has active hemoptysis (bright red blood at =0.5 teaspoon) within 3 weeks prior to the
first dose of study intervention or tumor bleeding within 2 weeks prior to
randomization

- 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 or cerebral vascular accident,
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 (HCV) [defined as HCV ribonucleic acid
(RNA) is detected] (hepatitis B and C testing is required at screening only when
mandated by local health authority)

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

- 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 or live attenuated 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/04/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/04/2025
Actual
Sample size
Target
Accrual to date
Final
842
Recruitment in Australia
Recruitment state(s)
NSW,QLD,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 Hospital ( Site 1602) - Westmead
Recruitment hospital [5] 0 0
Mater Misericordiae Ltd ( Site 1608) - South Brisbane
Recruitment hospital [6] 0 0
Monash Health ( Site 1606) - Clayton
Recruitment hospital [7] 0 0
Epworth Freemasons Hospital ( Site 1609) - Melbourne
Recruitment hospital [8] 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
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3002 - Melbourne
Recruitment postcode(s) [8] 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
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
North Dakota
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
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
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
La Rioja
Country [21] 0 0
Austria
State/province [21] 0 0
Steiermark
Country [22] 0 0
Austria
State/province [22] 0 0
Tirol
Country [23] 0 0
Austria
State/province [23] 0 0
Wien
Country [24] 0 0
Belgium
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Antwerpen
Country [25] 0 0
Belgium
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Bruxelles-Capitale, Region De
Country [26] 0 0
Belgium
State/province [26] 0 0
Oost-Vlaanderen
Country [27] 0 0
Belgium
State/province [27] 0 0
West-Vlaanderen
Country [28] 0 0
Brazil
State/province [28] 0 0
Ceara
Country [29] 0 0
Brazil
State/province [29] 0 0
Goias
Country [30] 0 0
Brazil
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Minas Gerais
Country [31] 0 0
Brazil
State/province [31] 0 0
Rio Grande Do Sul
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Brazil
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Sao Paulo
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Brazil
State/province [33] 0 0
Rio de Janeiro
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Canada
State/province [34] 0 0
Alberta
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Canada
State/province [35] 0 0
British Columbia
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
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Canada
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Quebec
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China
State/province [38] 0 0
Anhui
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China
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Beijing
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China
State/province [40] 0 0
Chongqing
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China
State/province [41] 0 0
Guangdong
Country [42] 0 0
China
State/province [42] 0 0
Guangxi
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China
State/province [43] 0 0
Hubei
Country [44] 0 0
China
State/province [44] 0 0
Hunan
Country [45] 0 0
China
State/province [45] 0 0
Jiangsu
Country [46] 0 0
China
State/province [46] 0 0
Shaanxi
Country [47] 0 0
China
State/province [47] 0 0
Shanghai
Country [48] 0 0
China
State/province [48] 0 0
Xinjiang
Country [49] 0 0
China
State/province [49] 0 0
Zhejiang
Country [50] 0 0
Germany
State/province [50] 0 0
Baden-Wurttemberg
Country [51] 0 0
Germany
State/province [51] 0 0
Bayern
Country [52] 0 0
Germany
State/province [52] 0 0
Hessen
Country [53] 0 0
Germany
State/province [53] 0 0
Nordrhein-Westfalen
Country [54] 0 0
Germany
State/province [54] 0 0
Thuringen
Country [55] 0 0
Germany
State/province [55] 0 0
Berlin
Country [56] 0 0
Ireland
State/province [56] 0 0
Cork
Country [57] 0 0
Ireland
State/province [57] 0 0
Dublin
Country [58] 0 0
Israel
State/province [58] 0 0
Central
Country [59] 0 0
Israel
State/province [59] 0 0
Tell Abib
Country [60] 0 0
Israel
State/province [60] 0 0
Haifa
Country [61] 0 0
Israel
State/province [61] 0 0
Ramat Gan
Country [62] 0 0
Italy
State/province [62] 0 0
Emilia-Romagna
Country [63] 0 0
Italy
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Roma
Country [64] 0 0
Italy
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Venezia
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Italy
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Arezzo
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Italy
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Bari
Country [67] 0 0
Italy
State/province [67] 0 0
Bologna
Country [68] 0 0
Italy
State/province [68] 0 0
Brindisi
Country [69] 0 0
Italy
State/province [69] 0 0
Catania
Country [70] 0 0
Italy
State/province [70] 0 0
Napoli
Country [71] 0 0
Japan
State/province [71] 0 0
Ehime
Country [72] 0 0
Japan
State/province [72] 0 0
Fukuoka
Country [73] 0 0
Japan
State/province [73] 0 0
Gunma
Country [74] 0 0
Japan
State/province [74] 0 0
Hokkaido
Country [75] 0 0
Japan
State/province [75] 0 0
Hyogo
Country [76] 0 0
Japan
State/province [76] 0 0
Kanagawa
Country [77] 0 0
Japan
State/province [77] 0 0
Okinawa
Country [78] 0 0
Japan
State/province [78] 0 0
Saitama
Country [79] 0 0
Japan
State/province [79] 0 0
Tokyo
Country [80] 0 0
Japan
State/province [80] 0 0
Niigata
Country [81] 0 0
Japan
State/province [81] 0 0
Osaka
Country [82] 0 0
Korea, Republic of
State/province [82] 0 0
Kyonggi-do
Country [83] 0 0
Korea, Republic of
State/province [83] 0 0
Seoul
Country [84] 0 0
Mexico
State/province [84] 0 0
Chiapas
Country [85] 0 0
Mexico
State/province [85] 0 0
Nuevo Leon
Country [86] 0 0
Mexico
State/province [86] 0 0
Chihuahua
Country [87] 0 0
Mexico
State/province [87] 0 0
Ciudad de Mexico
Country [88] 0 0
Mexico
State/province [88] 0 0
Mexico City
Country [89] 0 0
Poland
State/province [89] 0 0
Dolnoslaskie
Country [90] 0 0
Poland
State/province [90] 0 0
Lodzkie
Country [91] 0 0
Poland
State/province [91] 0 0
Malopolskie
Country [92] 0 0
Poland
State/province [92] 0 0
Mazowieckie
Country [93] 0 0
Poland
State/province [93] 0 0
Podlaskie
Country [94] 0 0
Poland
State/province [94] 0 0
Slaskie
Country [95] 0 0
Poland
State/province [95] 0 0
Wielkopolskie
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Krasnoyarskiy Kray
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Moskva
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Samarskaya Oblast
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Sankt-Peterburg
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Tatarstan, Respublika
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Tomskaya Oblast
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
Country [103] 0 0
Spain
State/province [103] 0 0
La Coruna
Country [104] 0 0
Spain
State/province [104] 0 0
Valenciana, Comunitat
Country [105] 0 0
Spain
State/province [105] 0 0
Cordoba
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Spain
State/province [106] 0 0
Madrid
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Spain
State/province [107] 0 0
Malaga
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taichung
Country [109] 0 0
Taiwan
State/province [109] 0 0
Taipei
Country [110] 0 0
Taiwan
State/province [110] 0 0
Taoyuan
Country [111] 0 0
Turkey
State/province [111] 0 0
Adana
Country [112] 0 0
Turkey
State/province [112] 0 0
Ankara
Country [113] 0 0
Turkey
State/province [113] 0 0
Antalya
Country [114] 0 0
Turkey
State/province [114] 0 0
Bursa
Country [115] 0 0
Ukraine
State/province [115] 0 0
Dnipropetrovska Oblast
Country [116] 0 0
Ukraine
State/province [116] 0 0
Ivano-Frankivska Oblast
Country [117] 0 0
Ukraine
State/province [117] 0 0
Kharkivska Oblast
Country [118] 0 0
Ukraine
State/province [118] 0 0
Khmelnytska Oblast
Country [119] 0 0
Ukraine
State/province [119] 0 0
Kyivska Oblast
Country [120] 0 0
Ukraine
State/province [120] 0 0
Odeska Oblast
Country [121] 0 0
Ukraine
State/province [121] 0 0
Kyiv
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Edinburgh, City Of
Country [123] 0 0
United Kingdom
State/province [123] 0 0
London, City Of
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Oxfordshire
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Middlesbrough
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

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).

As of Amendment 7 eligible participants on study completion will be able to transition to an
extension study, if available, in which they can continue to receive pembrolizumab
monotherapy, lenvatinib monotherapy, or a combination of both pembrolizumab and lenvatinib as
received in the parent study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03884101
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03884101