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Phase 3 Completed N=827 Randomized Treatment

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])

Source: ClinicalTrials.gov NCT03517449 ↗
Enrolled (actual)
827
Serious AEs
44.2%
Results posted
Nov 2021
Primary outcomePrimary: 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
◆ Published Evidence
Highly cited
150citations · ~50 / year
Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · Open access · Likely link

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.

Linked Publications (5)

  • Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 150 citations · Open access · Likely link
  • Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice.
    European journal of cancer (Oxford, England : 1990) · 2023 · 17 citations · Open access · Likely link
  • Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician's choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer.
    Journal of gynecologic oncology · 2024 · 15 citations · Open access · Likely link
  • Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab.
    The oncologist · 2024 · 13 citations · Open access · Likely link
  • Lenvatinib plus pembrolizumab in participants with advanced or recurrent endometrial cancer: Study 309/KEYNOTE-775 and ENGOT-en9/LEAP-001 post-(neo)adjuvant therapy outcomes.
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2026 · 0 citations · Likely link

Outcome Measures

OutcomeResultp-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

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03517449) and the linked publication. 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. Informational only — not medical advice.

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