The phase 3 LEAP-001 trial (NCT03884101) evaluated the efficacy of pembrolizumab (Keytruda) combined with lenvatinib (Lenvima) versus platinum-based chemotherapy with carboplatin and paclitaxel as frontline therapy in patients with advanced or recurrent endometrial cancer. The trial focused on patients whose disease was mismatch repair proficient (pMMR)/not microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR/MSI-H).
Despite earlier promising results from the phase 1b/2 KEYNOTE-146/Study 111 trial (NCT02501096) and the phase 3 KEYNOTE-775/Study 309 trial (NCT03517449), which showed improved progression-free survival (PFS) and overall survival (OS) in patients with advanced endometrial cancer, the LEAP-001 trial did not meet its primary endpoints of PFS and OS.
The safety profile of the pembrolizumab plus lenvatinib combination was consistent with previous trials. The trial's full data evaluation is ongoing, and results will be shared with the scientific community upon completion. These findings do not affect the current approved indications for the combination or other ongoing clinical trials within the LEAP program.
Dr. Gregory Lubiniecki, vice president of Global Clinical Development at Merck Research Laboratories, expressed disappointment but reaffirmed confidence in the combination's benefit for certain patients with previously treated advanced endometrial carcinoma. Dr. Corina Dutcus, senior vice president of Oncology Global Clinical Development at Eisai Inc, highlighted the challenges of treating advanced or recurrent endometrial carcinoma and the importance of continued research.
Eligibility for the LEAP-001 trial required patients to have stage III, IV, or recurrent endometrial cancer, among other criteria. The trial's design included dual primary endpoints of PFS and OS, with secondary endpoints focusing on objective response rate, quality of life, and safety.
Approximately 842 patients were randomized to receive either pembrolizumab plus lenvatinib or carboplatin and paclitaxel. The trial's outcomes underscore the complexity of treating advanced or recurrent endometrial cancer and the need for further research to improve patient outcomes.
