MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has a histologically confirmed new diagnosis of Endometrial Carcinoma or Carcinosarcoma (Mixed Mullerian Tumor) and: a) Has undergone curative intent surgery that included hysterectomy and bilateral salpingo-oophorectomy. Pelvic lymph node sampling, para-aortic lymph node sampling, including sentinel lymph node, and lymph node dissection are optional. b) Is at high risk for recurrence following treatment with curative intent surgery, ie, one of the following: - FIGO (2009) Surgical Stage I/II with myometrial invasion of non-endometrioid histology including serous adenocarcinoma, clear cell carcinoma, mucinous carcinoma, mixed epithelial carcinoma, dedifferentiated/undifferentiated carcinoma, squamous cell carcinoma, or carcinosarcoma - FIGO (2009) Surgical Stage I/II with myometrial invasion of any histology with known aberrant p53 expression or p53 mutation - FIGO (2009) Surgical Stage III or IVA of any histology 2. Is disease-free with no evidence of loco-regional disease or distant metastasis post operatively and on imaging. 3. Has not received any radiation or systemic therapy, including immunotherapy or hormonal therapy, in any setting including the neoadjuvant setting for EC. 4. Is female and at least 18 years of age at the time of providing documented informed consent. 5. Has ECOG performance status of 0 or 1 within 7 days before randomization. 6. The participant (or legally acceptable representative) has provided documented informed consent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research. 7. Submission of a tumor tissue sample from current diagnosis of Endometrial Carcinoma or Carcinosarcoma for prospective determination of histology and MMR status by central vendor is required for all participants. 8. Have adequate organ function. Specimens must be collected within 7 days before randomization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 495 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 495
Exclusion criteria
Exclusion criteria: 1. Has recurrent endometrial carcinoma or carcinosarcoma. 2. Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed. 3. Has FIGO (2009) Surgical Stage I/II EC of endometrioid histology without a known aberrant p53 expression or p53 mutation. 4. Is known to have a POLE mutation. 5. Has FIGO Stage IVB disease of any histology even if there is no evidence of disease after surgery. 6. Has residual tumor whether measurable or non-measurable after surgery. 7. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years. 8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). 9. Has received a live vaccine within 30 days before the first dose of study intervention. 10. Has a known intolerance to study intervention (or any of the excipients). 11. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. 12. Has any contraindication to the use of carboplatin or paclitaxel. 13. 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 the first dose of study intervention. 14. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 15. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 16. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 17. Has an active infection requiring systemic therapy. 18. Has a known history of HIV infection. 19. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 20. 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. 21. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study. 22. Has had an allogenic tissue/solid organ transplant. 23. Has not recovered adequately from surgery and/or any complications from the surgery. 24. Is breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare pembrolizumab with placebo, both in combination with adjuvant chemotherapy +/- XRT, with respect to disease-free survival (DFS) assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence. 2. To compare pembrolizumab with placebo, both in combination with adjuvant chemotherapy +/- XRT, with respect to overall survival (OS). ;Secondary Objective: 1. To compare pembrolizumab with placebo, both in combination with adjuvant chemotherapy +/- XRT, with respect to DFS assessed radiographically by blinded independent central review or by histopathologic confirmation of disease recurrence. 2. To compare pembrolizumab with placebo, both in combination with adjuvant chemotherapy +/- XRT, with respect to OS and DFS assessed radiographically by the investigator or by histopathologic confirmation of disease recurrence by PD-L1 status, and by tumor mutation burden (TMB) status. 3. To evaluate the safety and tolerability of pembrolizumab in combination with adjuvant chemotherapy +/- XRT. 4. To compare pembrolizumab with placebo, both in combination with adjuvant chemotherapy +/- XRT, with respect to change from baseline score in the EORTC Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (QoL) scale and Physical Function subscale, and the EORTC endometrial cancer-specific QoL module (EORTC QLQ-EN24). ;Primary end point(s): 1. Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence 2. Overall Survival (OS) ;Timepoint(s) of evaluation of this end point: 1. Up to approximately 42 months 2. Up to approximately 54 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Disease-Free Survival (DFS) as Assessed Radiographically by Blinded Independent Central Review (BICR) or by Histopathologic Confirmation of Suspected Disease Recurrence 2. Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Combined Positivity Score (CPS)-Determined Programmed Cell Death 1 Ligand 1 (PD-L1) Status 3. Overall Survival (OS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Combined Positivity Score (CPS)-Determined Programmed Cell Death 1 Ligand 1 (PD-L1) Status 4.Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Tumor Mutation Burden (TMB) Status 5.Overall Survival (OS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Tumor Mutation Burden (TMB) Status 6. Number of Participants Who Experience One or More Adverse Events (AEs) 7. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) 8. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (QoL) Score 9. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function Score 10. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Endometrial Cancer (EORTC QLQ-EN24) Score ;Timepoint(s) of evaluation of this end point: 1. Up to approximately 42 months 2. Up to approximately 42 months 3. Up to approximately 54 months 4. Up to approximately 42 months 5. Up to approximately 54 months 6. Up to approximately 54 months 7. Up to approximately 52 weeks 8. U | — |
Countries
Argentina, Austria, Belgium, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Democratic People's Republic of, Mexico, Norway, Poland, Russian Federation, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operation
Merck Sharp & Dohme Corp.
Outcome results
None listed