Clinical Trials /

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

NCT03884101

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).

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001)
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: 7902-001
  • SECONDARY ID: 2018-003009-24
  • SECONDARY ID: MK-7902-001
  • SECONDARY ID: ENGOT-en9
  • SECONDARY ID: 194710
  • NCT ID: NCT03884101

Conditions

  • Endometrial Neoplasms

Interventions

DrugSynonymsArms
LenvatinibE7080, MK-7902, LENVIMA®Lenvatinib + Pembrolizumab
PembrolizumabMK-3475, KEYTRUDA®Lenvatinib + Pembrolizumab
PaclitaxelTAXOL®, ONXAL®Paclitaxel + Carboplatin
CarboplatinPARAPLATIN®Paclitaxel + Carboplatin

Purpose

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 Arms

NameTypeDescriptionInterventions
Lenvatinib + PembrolizumabExperimental
  • Lenvatinib
  • Pembrolizumab
Paclitaxel + CarboplatinActive Comparator
  • Paclitaxel
  • Carboplatin

Eligibility Criteria

        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; and may have received prior hormonal therapy for treatment of endometrial
             carcinoma, provided that it was discontinued ≥1 week prior to randomization)

          -  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 and 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

        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, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Time Frame:Up to approximately 31 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Time Frame:Up to approximately 31 months
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and designated time points up to 27 months
Safety Issue:
Description: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.
Measure:Percentage of participants experiencing an adverse event (AE)
Time Frame:Up to approximately 27 months (through 90 days after the last dose of study treatment)
Safety Issue:
Description: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.
Measure:Percentage of participants experiencing a serious adverse event (SAE)
Time Frame:Up to approximately 28 months (through 120 days after the last dose of study treatment)
Safety Issue:
Description: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.
Measure:Percentage of participants experiencing an immune-related AE (irAE)
Time Frame:Up to approximately 27 months (through 90 days after the last dose of study treatment)
Safety Issue:
Description:Immune-related AEs will be monitored in both arms.
Measure:Percentage of participants discontinuing from study treatment due to an AE(s)
Time Frame:Up to approximately 24 months (through the last dose of study treatment)
Safety Issue:
Description:Discontinuations related to AEs will be monitored in both arms.
Measure:Plasma clearance of lenvatinib versus time
Time Frame:At designated timepoints through Cycle 2 Day 1 (each cycle is 21 days)
Safety Issue:
Description:The clearance of lenvatinib over time will be determined.
Measure:Area under the plasma concentration-time curve (AUC) of lenvatinib
Time Frame:At designated timepoints through Cycle 2 Day 1 (each cycle is 21 days)
Safety Issue:
Description:The AUC of lenvatinib will be determined in all participants.
Measure:Plasma concentration of lenvatinib
Time Frame:At designated timepoints through Cycle 2 Day 1 (each cycle is 21 days)
Safety Issue:
Description:The plasma concentration of lenvatinib versus time will be determined.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Last Updated

January 7, 2020