Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001) - China Extension Study (LEAP-001)

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)

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.

Study Overview

• Status: Completed
• Conditions: Endometrial Neoplasms
• Intervention / Treatment: Drug: Lenvatinib; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

Detailed Description

This China extension study will include participants previously enrolled in China in the global study for MK-7902-001 (NCT03884101) plus those enrolled during the China extension enrollment period.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230031
      • Anhui Cancer Hospital-Gynecological Oncology ( Site 2509)
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100032
      • Beijing Obstetrics and Gynecology Hospital Capital Medical University ( Site 2505)
    • Beijing, Beijing Municipality, China, 100032
      • Peking Union Medical College Hospital ( Site 2501)
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital ( Site 2504)
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing Cancer Hospital ( Site 2513)
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The First Affiliated hospital of Xiamen University-Obstetrics and gynecology department ( Site 2522)
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital.Sun Yat-sen University ( Site 2507)
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guang Xi Tumour Hospital, Department of Chemotherapy ( Site 2517)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital ( Site 2520)
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital ( Site 2510)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central-South University ( Site 2512)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 2523)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Nanjing Maternity and Child Health Care Hospital ( Site 2508)
  • Jiangxi
    • Nanchang, Jiangxi, China, 530021
      • Jiangxi Maternal and Child Health Hospital ( Site 2519)
  • Jilin
    • Changchun, Jilin, China, 130012
      • The First Hospital Of Jilin University ( Site 2518)
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The first affiliated Hospital of Xi an Jiaotong University ( Site 2502)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 2500)
    • Shanghai, Shanghai Municipality, China, 200090
      • Obstetrics and Gynecology Hosp. Fudan University ( Site 2503)
    • Shanghai, Shanghai Municipality, China, 201204
      • Shanghai First Maternity and Infant Hospital ( Site 2524)
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830054
      • The First Affiliated Hospital of Xinjiang Medical University ( Site 2515)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Women s Hospital School of Medicine Zhejiang University ( Site 2511)
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 2506)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Exclusion Criteria:

• Has carcinosarcoma (malignant mixed Műllerian 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 of ≥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, 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 (hepatitis B and C testing is required at screening)
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib + Pembrolizumab; Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.	Drug: Lenvatinib; Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.; Other Names: E7080, MK-7902, LENVIMA®; Biological: Pembrolizumab; Pembrolizumab 200 mg IV infusion given on Day 1 of each cycle.; Other Names: MK-3475, KEYTRUDA®
Active Comparator: Paclitaxel + Carboplatin; Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle.	Drug: Paclitaxel; Paclitaxel 175 mg/m^2 IV infusion given on Day 1 of each cycle.; Other Names: TAXOL®, ONXAL®; Drug: 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.; Other Names: PARAPLATIN®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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) in Mismatch Repair Proficient (pMMR) Participants	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS of pMMR participants was presented.	Up to approximately 45 months
PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants	PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS of all randomized participants was presented.	Up to approximately 45 months
Overall Survival (OS) in pMMR Participants	OS was measured from the time of randomization up to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for pMMR participants is presented.	Up to approximately 45 months
OS in All Randomized Participants	OS was measured from the time of randomization up to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all randomized participants is presented.	Up to approximately 45 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants	ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of pMMR participants who experienced a CR or PR is presented.	Up to approximately 45 months
ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants	ORR was defined as the percentage of participants who had a CR: Disappearance of all target lesions or a PR: At least a 30% decrease in the sum of diameters of target lesions as assessed using RECIST 1.1. The percentage of all randomized participants who experienced a CR or PR is presented.	Up to approximately 45 months
Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score in pMMR Participants	The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" were scored on a 7-point scale (1=Very Poor to 7=Excellent). The combined score of Global Health Status (EORTC QLQ-C30 Item 29) and Quality of Life (EORTC QLQ-C30 Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores ranged from 0-100. A higher score indicates a better outcome. The change from baseline in GHS/QoL combined score was reported for each arm.	Baseline and up to approximately 18 weeks
Mean Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Score in All Randomized Participants	The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" were scored on a 7-point scale (1=Very Poor to 7=Excellent). The combined score of Global Health Status (EORTC QLQ-C30 Item 29) and Quality of Life (EORTC QLQ-C30 Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores ranged from 0-100. A higher score indicates a better outcome. The change from baseline in GHS/QoL combined score was reported for each arm.	Baseline and up to approximately 18 weeks
Number 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.	From first dose date to 120 days after last dose date (up to approximately 58 months)
Number of Participants Experiencing a Serious Adverse Event (SAE)	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. 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.	From first dose date to 120 days after last dose date (up to approximately 58 months)
Number of Participants Experiencing an Immune-related AE (irAE)	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. Immune-related AEs (irAEs) were AEs that were considered immune-mediated or potentially immune-mediated and are well-documented for pembrolizumab. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. The number of participants with irAEs was reported for each arm.	From first dose date to 120 days after last dose date (up to approximately 58 months)
Number of Participants Discontinuing From Study Treatment Due to an AE(s)	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. The number of participants who discontinued study treatment due to an AE was reported for each arm.	From first dose date to last dose date (up to approximately 54 months)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Eisai Inc.
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): January 14, 2025

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Estimated): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel; pembrolizumab; lenvatinib
• Other Study ID Numbers: 7902-001 China Extension; MK-7902-001 (Other Identifier: MSD); ENGOT-en9 (Other Identifier: European Network for Gynaecological Oncological Trial groups); 194710 (Registry Identifier: JAPIC-CTI); 2023-505614-17 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes