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323 ENGOT-en9/LEAP-001: a phase 3 study of first-line pembrolizumab plus lenvatinib compared with chemotherapy in advanced or recurrent endometrial cancer
  1. L Randall1,
  2. C Marth2,
  3. C Vulsteke3,
  4. M Jesús Rubio4,
  5. V Makker5,
  6. I Braicu6,
  7. I McNeish7,
  8. R Madry8,
  9. A Ayhan9,
  10. K Hasegawa10,
  11. X Wu11,
  12. L Dutta12,
  13. C Xu13,
  14. S Keefe13,
  15. J Lee13 and
  16. S Pignata14
  1. 1Virginia Commonwealth University Medical Center, USA
  2. 2Medical University of Innsbruck, Austria
  3. 3AZ Maria Middelares, Belgium
  4. 4Reina Sofía de Córdoba, Spain
  5. 5Memorial Sloan Kettering Cancer Center, USA
  6. 6Charité Universitätsmedizin, Germany
  7. 7Imperial College, UK
  8. 8Uniwersytet Medyczny im K. Marcinkowskiego w Poznaniu, Poland
  9. 9Ankara Baskent University Hospital, Turkey
  10. 10Saitama Medical University, Japan
  11. 11Fudan University Shanghai Cancer Center, China
  12. 12Eisai Inc., USA
  13. 13Merck and Co., Inc., USA
  14. 14National Cancer Institute, Italy


Background Prognosis and OS are poor in patients with advanced or recurrent endometrial cancer (EC). First-line standard of care for these patients is paclitaxel-carboplatin chemotherapy; however, more effective and tolerable therapies are needed. In the phase 1b/2 trial KEYNOTE-146, which assessed the PD-1 inhibitor pembrolizumab combined with the multikinase inhibitor lenvatinib, an ORR of 38% was observed in patients with previously treated advanced EC. ENGOT-en9/LEAP-001 (NCT03884101) is a randomized, open-label, active-controlled, phase 3 study investigating pembrolizumab + lenvatinib vs chemotherapy in patients with EC.

Trial design Patients with newly diagnosed advanced (stage III-IV) or recurrent EC not previously treated with antiangiogenic agents; systemic chemotherapy (unless within a chemoradiation regimen); PD-1, PD-L1, or PD-L2 inhibitors; or other T-cell receptor–targeted therapies will be eligible. Patients will be randomized 1:1 to receive pembrolizumab 200 mg Q3W + lenvatinib 20 mg daily or paclitaxel 175 mg/m2 Q3W + carboplatin AUC 6 Q3W. Randomization will be stratified by proficient vs deficient mismatch repair (pMMR vs dMMR) status. The pMMR population will be further stratified by prior chemoradiation (yes/no), measurable disease (yes/no), and ECOG performance status (0/1). Patients will receive treatment for ≤35 cycles of pembrolizumab vs 7 cycles of chemotherapy or until initiation of a new anticancer treatment, unacceptable AEs, or withdrawal of consent. Primary endpoints are PFS (per RECIST v1.1 by blinded independent central review) and OS. Secondary endpoints are ORR, health-related QOL, safety/tolerability, and lenvatinib pharmacokinetics. Exploratory endpoints are disease control rate, clinical benefit rate, and duration of response. Enrollment is ongoing.

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