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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
842
Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.
Pembrolizumab 200 mg intravenous (IV) infusion given on Day 1 of each cycle.
Paclitaxel 175 mg/m\^2 IV infusion given on Day 1 of each cycle.
Carboplatin 10 mg/mL IV infusion at a total dose of are-under-the-curve (AUC) 6 (per Calvert's formula) given on Day 1 of each cycle.
University of South Alabama, Mitchell Cancer Institute ( Site 0245)
Mobile, Alabama, United States
Arizona Oncology Associates PC- HOPE ( Site 8005)
Tucson, Arizona, United States
UCLA Hematology and Oncology Clinic (Westwood) ( Site 0233)
Los Angeles, California, United States
University of Colorado Cancer Center ( Site 0204)
Aurora, Colorado, United States
Smilow Cancer Hospital at Yale New Haven ( Site 0202)
New Haven, Connecticut, United States
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
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.
Time frame: Up to approximately 44 months
PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
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.
Time frame: Up to approximately 44 months
Overall Survival (OS) in pMMR Participants
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.
Time frame: Up to approximately 51 months
OS in All Randomized Participants
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.
Time frame: Up to approximately 51 months
Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants
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.
Time frame: Up to approximately 51 months
ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
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.
Time frame: Up to approximately 51 months
Mean Change From Baseline in the Global Health Status/Quality of Life Score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) in pMMR Participants
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.
Time frame: Baseline and up to approximately 18 weeks
Mean Change From Baseline in the Global Health Status/Quality of Life Score of the EORTC QLQ-C30 in All Randomized Participants
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 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.
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University of Miami Health System ( Site 0249)
Miami, Florida, United States
Georgia Cancer Center at Augusta University ( Site 0222)
Augusta, Georgia, United States
Women's Cancer Care ( Site 0208)
Covington, Louisiana, United States
Maine Medical Partners ( Site 0217)
Scarborough, Maine, United States
Minnesota Oncology Hematology, PA ( Site 8003)
Minneapolis, Minnesota, United States
...and 185 more locations
Time frame: Baseline and up to approximately 18 weeks
Number of Participants Who Experienced an Adverse Event (AE)
An AE was 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 AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). Per protocol, the number of participants who experienced one or more AEs was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms.
Time frame: Up to approximately 68 months
Number of Participants Who Experienced a Serious Adverse Event (SAE)
An SAE was an AE that resulted in death, was life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability, was a congenital birth defect, or was another important medical event. Per protocol, the number of participants who experienced one or more SAEs was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms.
Time frame: Up to approximately 68 months
Number of Participants Who Experienced an Immune-Related Adverse Event (irAE)
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. Per protocol, the number of participants who experienced one or more irAEs was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms.
Time frame: Up to approximately 68 months
Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was 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 AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). Per protocol, the number of participants who discontinued any study intervention (pembrolizumab and/or lenvatinib or paclitaxel and/or carboplatin) due to an AE was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms.
Time frame: Up to approximately 68 months