FDA approves Keytruda + Lenvima to treat advanced endometrial cancer – Merck Inc.+ Eisai

The FDA has approved pembrolizumab (Keytruda) in combination with lenvatinib (Lenvima) for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
The FDA had granted accelerated approval on September 17, 2019 to pembrolizumab with lenvatinib for advanced endometrial carcinoma.

Study 309/KEYNOTE-775 (NCT03517449) was a multicenter, open-label, randomized, active-controlled trial required to confirm the clinical benefit of this accelerated approval.

Study 309/KEYNOTE-775 enrolled 827 patients with advanced endometrial carcinoma previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including neoadjuvant and adjuvant treatments. Patients were randomized (1:1) to either pembrolizumab 200 mg intravenously every 3 weeks with lenvatinib 20 mg orally once daily or investigator’s choice of doxorubicin or paclitaxel. The major efficacy outcome measures were progression-free survival (PFS), as assessed by blinded independent central review (BICR) , and overall survival (OS) . Additional efficacy outcome measures included objective response rate (ORR) and duration of response (DOR), also BICR-assessed.

For patients with advanced endometrial cancer that is not MSI-H or dMMR, the median PFS was 6.6 months (95% CI: 5.6, 7.4) for patients in the pembrolizumab and lenvatinib group and 3.8 months (95% CI: 3.6, 5.0) for those receiving investigator’s choice chemotherapy (HR 0.60; 95% CI: 0.50, 0.72; p<0.0001). Median OS was 17.4 months (95% CI: 14.2, 19.9) and 12.0 months (95% CI: 10.8, 13.3), respectively (HR 0.68; 95% CI: 0.56, 0.84; p=0.0001). ORR was 30% (95% CI: 26, 36) and 15% (95% CI: 12, 19), respectively (p<0.0001). Median DOR was 9.2 months (1.6+, 23.7+) and 5.7 months (0.0+, 24.2+).