Phase 3
N=827
Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775])
Endometrial Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT03517449 ↗Enrolled (actual)
827
Serious AEs
44.2%
Results posted
Nov 2021
Primary outcome: Primary: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Mismatch Repair Proficient (pMMR) Participants — 6.6; 3.8 Months — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pembrolizumab (Drug); Lenvatinib (Drug); Paclitaxel (Drug); Doxorubicin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Eisai Inc.
- Primary completion
- Mar 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Mismatch Repair Proficient (pMMR) Participants |
6.6; 3.8 | < 0.0001 sig |
| PRIMARY PFS Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on BICR in All-comer Participants |
7.2; 3.8 | < 0.0001 sig |
| PRIMARY Overall Survival (OS) in pMMR Participants |
18.0; 12.2 | < 0.0001 sig |
| PRIMARY OS in All-comer Participants |
18.7; 11.9 | < 0.0001 sig |
| SECONDARY Objective Response Rate (ORR) in pMMR Participants |
30.3; 15.1 | < 0.0001 sig |
| SECONDARY ORR in All-comer Participants |
31.9; 14.7 | < 0.0001 sig |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) in pMMR Participants |
-6.80; -7.96 | = 0.5316 |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) in All-comer Participants |
-5.97; -6.98 | = 0.5460 |
| SECONDARY Number of Partricipants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Immune-Related Adverse Events (irAEs) |
237; 121 | — |
| SECONDARY Number of Participants Who Discontinued Study Treatment Due to a TEAE in pMMR Participants |
140; 42 | — |
| SECONDARY Number of Participants Who Discontinued Study Treatment Due to a TEAE in All-comer Participants |
180; 49 | — |
| SECONDARY Time to Treatment Failure Due to Toxicity in pMMR Participants |
429.6; 260.1 | — |
| SECONDARY Time to Treatment Failure Due to Toxicity in All-comer Participants |
456.5; 259.7 | — |
| SECONDARY Plasma Concentration of Lenvatinib Versus Time in All-comer Participants |
152; 258; 89.1; 310; 67.2; 151 | — |
| SECONDARY Plasma Concentration of Lenvatinib Versus Time in pMMR Participants |
140; 283; 93.8; 335; 67.9; 153 | — |
| SECONDARY Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib |
4.69 | — |
| SECONDARY Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib |
4134 | — |
Summary
This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) versus treatment of physician's choice (doxorubicin or paclitaxel) for the treatment of advanced endometrial cancer. Participants will be randomly assigned to receive either pembrolizumab and lenvatinib or treatment of physician's choice. The primary study hypothesis is that pembrolizumab in combination with lenvatinib prolongs progression free survival (PFS) and overall survival (OS) when compared to treatment of physician's choice.
Eligibility Criteria
Inclusion Criteria
- Has a histologically confirmed diagnosis of endometrial carcinoma (EC)
- Documented evidence of advanced, recurrent or metastatic EC.
- Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting.
Note: There is no restriction regarding prior hormonal therapy.
- Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.
- Has at least 1 measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.
- Is not pregnant, breastfeeding, and agrees to use a highly effective method of contraception during the treatment period and for at least 120 days (for participants treated with lenvatinib plus pembrolizumab) or at least 180 days (for participants treated with treatment of physician's choice [TPC]) after the last dose of study treatment.
Exclusion Criteria
- Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
- Has unstable central nervous system (CNS) metastases.
- Has active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within 24 months of study start.
- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
- Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
- Has radiographic evidence of major blood vessel invasion/infiltration.
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment.
- Has a history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment.
- Has an active infection requiring systemic treatment.
- Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
- Is positive for Human Immunodeficiency Virus (HIV).
- Has active Hepatitis B or C.
- Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- 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 study start -Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years.
- Is pregnant or breastfeeding.
- Has had an allogenic tissue/solid organ transplant.
- Has received >1 prior systemic chemotherapy regimen (other than adjuvant or neoadjuvant) for Endometrial Cancer. Participants may receive up to 2 regimens of platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or adjuvant treatment setting.
- Has received prior anticancer treatment within 28 days of study start. All acute toxicities related to prior treatments must be resolved to Grade ≤1, except for alopecia and Grade ≤2 peripheral neuropathy.
- Has received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has received prior treatment with an agent direc
Data sourced from ClinicalTrials.gov (NCT03517449). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.