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NCT04865289: LEAP-001

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

Completed Phase 3 Results posted Last updated 2 December 2025
What this trial tests

Phase 3 trial testing Lenvatinib in Endometrial Neoplasms in 130 participants. Completed in 14 January 2025.

Timeline
22 October 2019
Primary endpoint
2 October 2023
14 January 2025

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment130
Start date22 October 2019
Primary completion2 October 2023
Estimated completion14 January 2025
Sites22 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, female only, with Endometrial Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Up to approximately 45 months

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab10.36.4 – 12.7
Paclitaxel + Carboplatin10.28.3 – 10.6
PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants Primary · Up to approximately 45 months

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab11.78.3 – 19.4
Paclitaxel + Carboplatin10.38.3 – 12.5
Overall Survival (OS) in pMMR Participants Primary · Up to approximately 45 months

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab37.119.5 – NA
Paclitaxel + CarboplatinNA21.7 – NA
OS in All Randomized Participants Primary · Up to approximately 45 months

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.

GroupValue95% CI
Lenvatinib + PembrolizumabNA29.8 – NA
Paclitaxel + CarboplatinNA25.1 – NA
Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants Secondary · Up to approximately 45 months

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab50.937.1 – 64.6
Paclitaxel + Carboplatin61.445.5 – 75.6
ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants Secondary · Up to approximately 45 months

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab56.944.7 – 68.6
Paclitaxel + Carboplatin66.152.2 – 78.2
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 Secondary · Baseline and up to approximately 18 weeks

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 ran

GroupValue95% CI
Lenvatinib + Pembrolizumab-7.00-12.49 – -1.51
Paclitaxel + Carboplatin-4.87-11.52 – 1.79
Mean Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Score in All Randomized Participants Secondary · Baseline and up to approximately 18 weeks

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 ran

GroupValue95% CI
Lenvatinib + Pembrolizumab-6.69-11.42 – -1.96
Paclitaxel + Carboplatin-5.96-11.65 – -0.26
Number of Participants Experiencing an Adverse Event (AE) Secondary · From first dose date to 120 days after last dose date (up to approximately 58 months)

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab72
Paclitaxel + Carboplatin56
Number of Participants Experiencing a Serious Adverse Event (SAE) Secondary · From first dose date to 120 days after last dose date (up to approximately 58 months)

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab40
Paclitaxel + Carboplatin17
Number of Participants Experiencing an Immune-related AE (irAE) Secondary · From first dose date to 120 days after last dose date (up to approximately 58 months)

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab49
Paclitaxel + Carboplatin10
Number of Participants Discontinuing From Study Treatment Due to an AE(s) Secondary · From first dose date to last dose date (up to approximately 54 months)

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.

GroupValue95% CI
Lenvatinib + Pembrolizumab32
Paclitaxel + Carboplatin8

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization to the date of death or last participant data collection (up to approximately 61 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lenvatinib + Pembrolizumab
Serious: 40/73 (55%)
Deaths: 34/74
Paclitaxel + Carboplatin
Serious: 17/56 (30%)
Deaths: 25/56

Serious adverse events (74 terms)

ReactionSystemLenvatinib + PembrolizumabPaclitaxel + Carboplatin
AnaemiaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
GranulocytopeniaBlood and lymphatic system disorders
MyelosuppressionBlood and lymphatic system disorders
Arteriosclerosis coronary arteryCardiac disorders
AscitesGastrointestinal disorders
PainGeneral disorders
CholecystitisHepatobiliary disorders
Hepatic function abnormalHepatobiliary disorders
PneumoniaInfections and infestations
CachexiaMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
ArrhythmiaCardiac disorders
Myocardial injuryCardiac disorders
MyocarditisCardiac disorders
HypophysitisEndocrine disorders
DiarrhoeaGastrointestinal disorders
Functional gastrointestinal disorderGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
PancreatitisGastrointestinal disorders
Pancreatitis acuteGastrointestinal disorders
Small intestinal perforationGastrointestinal disorders
DeathGeneral disorders
Other adverse events (88 terms — click to expand)

ReactionSystemLenvatinib + PembrolizumabPaclitaxel + Carboplatin
ProteinuriaRenal and urinary disorders
HypertensionVascular disorders
AlopeciaSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
AnaemiaBlood and lymphatic system disorders
White blood cell count decreasedInvestigations
Neutrophil count decreasedInvestigations
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
HypoaesthesiaNervous system disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Urinary tract infectionInfections and infestations
Lipase increasedInvestigations
Weight decreasedInvestigations
MalaiseGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HaematuriaRenal and urinary disorders
Blood creatinine increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Blood thyroid stimulating hormone increasedInvestigations
HypertriglyceridaemiaMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
Upper respiratory tract infectionInfections and infestations
Blood bilirubin increasedInvestigations
HyperuricaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders

Most-reported serious reactions: Anaemia, Platelet count decreased, Granulocytopenia, Myelosuppression, Arteriosclerosis coronary artery, Ascites, Pain, Cholecystitis.

Data from ClinicalTrials.gov NCT04865289 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  2. Immunotherapy in endometrial cancer.
    Mahdi H, Chelariu-Raicu A, Slomovitz BM. · · 2023 · cited 52× · PMID 36878570 · DOI 10.1136/ijgc-2022-003675
  3. The roles of TGF-β and VEGF pathways in the suppression of antitumor immunity in melanoma and other solid tumors.
    Bu MT, Chandrasekhar P, Ding L, Hugo W. · · 2022 · cited 51× · PMID 35577211 · DOI 10.1016/j.pharmthera.2022.108211
  4. Immune checkpoint blockades in gynecological cancers: A review of clinical trials.
    Peng H, He X, Wang Q. · · 2022 · cited 38× · PMID 35751489 · DOI 10.1111/aogs.14412
  5. Trial Watch: combination of tyrosine kinase inhibitors (TKIs) and immunotherapy.
    Petrazzuolo A, Maiuri MC, Zitvogel L, Kroemer G, et al · · 2022 · cited 23× · PMID 35655707 · DOI 10.1080/2162402x.2022.2077898
  6. How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review.
    Maiorano BA, Maiorano MFP, Cormio G, Maglione A, et al · · 2022 · cited 19× · PMID 35494078 · DOI 10.3389/fonc.2022.844801
  7. Pembrolizumab in endometrial cancer: Where we stand now.
    Aravantinou-Fatorou A, Andrikopoulou A, Liontos M, Fiste O, et al · · 2021 · cited 12× · PMID 34691248 · DOI 10.3892/ol.2021.13082
  8. Combined use of pembrolizumab and lenvatinib: A review.
    Eisinger C, Muluneh B. · · 2023 · cited 9× · PMID 37231712 · DOI 10.1177/10781552231178461

Verify or expand the search:

Other trials of Lenvatinib

Trials testing the same drug.

Other recruiting trials for Endometrial Neoplasms

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04865289.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing