advanced or recurrent endometrial carcinoma
Conditions
Interventions
investigational material(s)
Generic name etc : lenvatinib + pembrolizumab
INN of investigational material : lenvatinib, pembrolizumab
Therapeutic category code : 429 Other antitumor agents
Dosage and
Sponsors
MSD K.K.
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1) Have Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is either measurable or non-measurable per RECIST 1.1 but radiographically apparent, as assessed by BICR. Notes about prior therapy: - May have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of a curative-intent resection. This prior chemotherapy may be given as treatment involving chemotherapy alone, concurrent chemoradiation, or as part of a sequential approach such as in a regimen involving concurrent chemoradiation followed by chemotherapy. - Instances in which both adjuvant and neoadjuvant systemic platinum-based chemotherapy are used will be counted as one line of chemotherapy. - May have received prior radiation with or without chemotherapy. - May have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued >=1 week prior to randomization. 2) Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion that was not previously irradiated, for determination of MMR status. 3) 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 4) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a. Is not a woman of childbearing potential (WOCBP). OR b. WOCBP must agree to use contraception as detailed in the study protocol throughout the treatment period and for at least 120 days after the last dose of pembrolizumab or 30 days after the last dose of lenvatinib, whichever is later, and for 180 days after the last dose of chemotherapy. 5) Have adequately controlled BP with or without antihypertensive medications, defined as BP <=150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization. 6) Has adequate organ function based on assessment within 7 days prior to the first dose of study intervention
Exclusion criteria
Exclusion criteria: 1) Has carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma or other high grade sarcomas, or endometrial stromal sarcomas. 2) Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment. 3) Has a known additional malignancy (other than endometrial carcinoma) that is progressing or has required active treatment in the last 3 years. 4) Has gastrointestinal malabsorption, or any other condition that might affect the absorption of lenvatinib. 5) Has a pre-existing Grade >=3 gastrointestinal or non-gastrointestinal fistula. 6) Has radiographic evidence of major blood vessel invasion/infiltration. 7) Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study intervention or tumor bleeding within 2 weeks prior to randomization. 8) 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. 9) Has an active infection (any infection requiring systemic treatment). 10) Has not recovered adequately from any toxicity and/or complications from major surgery prior to randomization. 11) Has a known history of human immunodeficiency virus (HIV) infection. 12) Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 13) Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis. 14) 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. 15) Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study 16) 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. 17) Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the 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. 18) Has received prior systemic chemotherapy in any setting for the treatment of endometrial carcinoma. note: prior chemotherapy administered as adjuvant therapy, neoadjuvant therapy, and/or concurrently with radiation is permitted. 19) Has received prior radiotherapy within 4 weeks prior to randomization. Participants must have r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy - Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ) as assessed by blinded independent central review (BICR) - Overall Survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy - Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR - European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 global health status - Adverse Event (AE) - Serious Adverse Event (SAE) - Immune-Related AE (irAE) - Study intervention discontinuations due to AEs | — |
Countries
Asia except Japan, Europe, Japan, North America, Oceania, South America
Contacts
Public ContactMSDJRCT inquiry mailbox
MSD K.K.
Outcome results
None listed