Advanced Endometrial Cancer MedDRA version: 20.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Eisai Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of endometrial carcinoma. 2. Documented evidence of advanced, recurrent or metastatic EC. 3. Radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for recurrent, metastatic or primary unresectable disease. - Participants who progress =65 years) yes F.1.3.1 Number of subjects for this age range 600
Exclusion criteria
Exclusion criteria: 1. Carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas. 2. Participants with CNS metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment. 3. Active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas, or basal or squamous cell carcinoma of the skin) within the past 24 months. 4. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib. 5. Radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy. 6. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug. 7. Significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability. 8. Active infection (any infection requiring systemic treatment). 9. Participants who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy. 10. Participants known to be positive for Human Immunodeficiency Virus (HIV). No HIV testing is required unless mandated by local heath authority. 11. Known active Hepatitis B or Hepatitis C. No testing for hepatitis B or C is required unless mandated by local health authority. 12. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis. 13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 15. 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 the first dose of study drug. 16. Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment. 17. Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 18. Greater than 1 prior systemic anticancer regimen (other than adjuvant or neoadjuvant) for advanced, recurrent, or metastatic endometrial cancer. 19. Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter). All acute toxicities related to prior treatments must be resolved to Grade =1, except
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate that lenvatinib in combination with pembrolizumab is superior to Treatment of Physician’s Choice (TPC) in improving progression-free survival (PFS). - To demonstrate that lenvatinib in combination with pembrolizumab is superior to TPC in improving overall survival (OS).;Secondary Objective: - To compare the objective response rate (ORR) of participants treated with lenvatinib in combination with pembrolizumab versus TPC by BICR. - To evaluate the impact of treatment on Health-Related Quality of Life (HRQoL) as assessed by using the global score of the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 for participants treated with lenvatinib in combination with pembrolizumab versus TPC. - To assess safety and tolerability of treatment with lenvatinib in combination with pembrolizumab versus TPC in pMMR participants and in all-comer participants. - To characterize the population pharmacokinetics (PK) of lenvatinib when co-administered with pembrolizumab in pMMR participants and in all-comer participants. refer to protocol for complete list;Primary end point(s): Progression-free survival: defined as the time from the date of randomization to the date of the first documentation of disease progression, as determined by blinded BICR of objective radiographic disease progression per RECIST 1.1 or death due to any cause(whichever occurs first). Overall Survival: defined as the time from the date of randomization to the date of death due to any cause. Participants who are lost to follow-up and those who are alive at the date of data cut-off will be censored at the date the participant was last known alive, or date of data cut-off, whichever occurs first.;Timepoint(s) of evaluation of this end point: An interim analysis for superiority of OS is planned for the study. The interim analysis will be conducted when there are approximately 363 death events observed in the pMMR participants, which is estimated to occ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective response rate (ORR) by BICR using RECIST 1.1. - Health-Related Quality of Life using the EORTC QLQ-C30. - Safety and tolerability of the two treatment groups. - Plasma concentration of lenvatinib versus time. - Model-predicted clearance and AUC for lenvatinib.;Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated at the final analysis and as required during the interim analysis. | — |
Countries
Argentina, Australia, Brazil, Canada, Colombia, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, New Zealand, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & dohme de España SA
Outcome results
None listed