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)
Overview
- Phase
- Phase 3
- Intervention
- Lenvatinib
- Conditions
- Endometrial Neoplasms
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 130
- Locations
- 22
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Detailed Description
This China extension study will include participants previously enrolled in China in the global study for MK-7902-001 (NCT03884101) plus those enrolled during the China extension enrollment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is either measurable or nonmeasurable 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 without concurrent chemotherapy; may have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued ≥1 week prior to randomization; and may have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy)
- •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, ≥30 days after lenvatinib, or ≥180 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 or any other condition that might affect the absorption of lenvatinib
- •Has a pre-existing Grade ≥3 gastrointestinal or nongastrointestinal fistula
- •Has radiographic evidence of major blood vessel invasion/infiltration
- •Has active hemoptysis (bright red blood of ≥0.5 teaspoon) within 3 weeks prior to the first dose of study intervention, or tumor bleeding within 2 weeks prior to randomization
- •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
- •Has any infection requiring systemic treatment
- •Has not recovered adequately from any toxicity and/or complications from major surgery prior to randomization
Arms & Interventions
Lenvatinib + Pembrolizumab
Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.
Intervention: Lenvatinib
Lenvatinib + Pembrolizumab
Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.
Intervention: Pembrolizumab
Paclitaxel + Carboplatin
Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle.
Intervention: Paclitaxel
Paclitaxel + Carboplatin
Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle.
Intervention: Carboplatin
Outcomes
Primary Outcomes
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
Time Frame: Up to approximately 45 months
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.
PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
Time Frame: Up to approximately 45 months
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.
Overall Survival (OS) in pMMR Participants
Time Frame: Up to approximately 45 months
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.
OS in All Randomized Participants
Time Frame: Up to approximately 45 months
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.
Secondary Outcomes
- Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants(Up to approximately 45 months)
- ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants(Up to approximately 45 months)
- Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score in pMMR Participants(Baseline and up to approximately 18 weeks)
- Mean Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Score in All Randomized Participants(Baseline and up to approximately 18 weeks)
- Number of Participants Experiencing an Adverse Event (AE)(From first dose date to 120 days after last dose date (up to approximately 58 months))
- Number of Participants Experiencing a Serious Adverse Event (SAE)(From first dose date to 120 days after last dose date (up to approximately 58 months))
- Number of Participants Experiencing an Immune-related AE (irAE)(From first dose date to 120 days after last dose date (up to approximately 58 months))
- Number of Participants Discontinuing From Study Treatment Due to an AE(s)(From first dose date to last dose date (up to approximately 54 months))