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

NCT04865289 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: 7902-001 China ExtensionMK-7902-001ENGOT-en91947102023-505614-17
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 22

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.

Conditions

Endometrial Neoplasms

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants

  Up to approximately 45 months

• ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants

  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

  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

  Baseline and up to approximately 18 weeks

• Number of Participants Experiencing an Adverse Event (AE)

  From first dose date to 120 days after last dose date (up to approximately 58 months)

Study Arms (2)

Lenvatinib + Pembrolizumab

EXPERIMENTAL

Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.

Drug: Lenvatinib; Biological: Pembrolizumab

Paclitaxel + Carboplatin

ACTIVE COMPARATOR

Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle.

Drug: Paclitaxel; Drug: Carboplatin

Interventions

Lenvatinib DRUG

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

Also known as: E7080, MK-7902, LENVIMA®

Lenvatinib + Pembrolizumab

Pembrolizumab BIOLOGICAL

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

Also known as: MK-3475, KEYTRUDA®

Lenvatinib + Pembrolizumab

Paclitaxel DRUG

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

Also known as: TAXOL®, ONXAL®

Paclitaxel + Carboplatin

Carboplatin DRUG

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.

Also known as: PARAPLATIN®

Paclitaxel + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Has carcinosarcoma (malignant mixed Műllerian tumor), endometrial leiomyosarcoma or other high grade sarcomas, or endometrial stromal sarcomas
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (22)

Anhui Cancer Hospital-Gynecological Oncology ( Site 2509)

Hefei, Anhui, 230031, China

Location

Beijing Obstetrics and Gynecology Hospital Capital Medical University ( Site 2505)

Beijing, Beijing Municipality, 100032, China

Location

Peking Union Medical College Hospital ( Site 2501)

Beijing, Beijing Municipality, 100032, China

Location

Beijing Cancer Hospital ( Site 2504)

Beijing, Beijing Municipality, 100142, China

Location

Chongqing Cancer Hospital ( Site 2513)

Chongqing, Chongqing Municipality, 400030, China

Location

The First Affiliated hospital of Xiamen University-Obstetrics and gynecology department ( Site 2522)

Xiamen, Fujian, 361003, China

Location

The First Affiliated Hospital.Sun Yat-sen University ( Site 2507)

Guangzhou, Guangdong, 510080, China

Location

Guang Xi Tumour Hospital, Department of Chemotherapy ( Site 2517)

Nanning, Guangxi, 530021, China

Location

Harbin Medical University Cancer Hospital ( Site 2520)

Harbin, Heilongjiang, 150081, China

Location

Hubei Cancer Hospital ( Site 2510)

Wuhan, Hubei, 430079, China

Location

Xiangya Hospital Central-South University ( Site 2512)

Changsha, Hunan, 410008, China

Location

Hunan Cancer Hospital ( Site 2523)

Changsha, Hunan, 410013, China

Location

Nanjing Maternity and Child Health Care Hospital ( Site 2508)

Nanjing, Jiangsu, 210011, China

Location

Jiangxi Maternal and Child Health Hospital ( Site 2519)

Nanchang, Jiangxi, 530021, China

Location

The First Hospital Of Jilin University ( Site 2518)

Changchun, Jilin, 130012, China

Location

The first affiliated Hospital of Xi an Jiaotong University ( Site 2502)

Xi'an, Shaanxi, 710061, China

Location

Fudan University Shanghai Cancer Center ( Site 2500)

Shanghai, Shanghai Municipality, 200032, China

Location

Obstetrics and Gynecology Hosp. Fudan University ( Site 2503)

Shanghai, Shanghai Municipality, 200090, China

Location

Shanghai First Maternity and Infant Hospital ( Site 2524)

Shanghai, Shanghai Municipality, 201204, China

Location

The First Affiliated Hospital of Xinjiang Medical University ( Site 2515)

Ürümqi, Xinjiang, 830054, China

Location

Women s Hospital School of Medicine Zhejiang University ( Site 2511)

Hangzhou, Zhejiang, 310006, China

Location

Zhejiang Cancer Hospital ( Site 2506)

Hangzhou, Zhejiang, 310022, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

lenvatinib; pembrolizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 29, 2021
• Study Start: October 22, 2019
• Primary Completion: October 2, 2023
• Study Completion: January 14, 2025
• Last Updated: December 2, 2025
• Results First Posted: October 18, 2024

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

CN (22)