A combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) demonstrated statistically significant improvement in overall survival, progression-free survival and objective response rate versus chemotherapy in patients with advanced endometrial cancer.
Keytruda is sponsored by Merck, and Lenvima is sponsored by Eisai.
The phase III KEYNOTE-775/Study 309 trial evaluating the investigational use of Keytruda, an anti-PD-1 therapy, plus Lenvima, the orally available multiple receptor tyrosine kinase inhibitor, met its dual primary endpoints of OS and PFS, and its secondary efficacy endpoint of ORR in patients with advanced endometrial cancer following at least one prior platinum-based regimen.
These positive results were observed in the mismatch repair proficient subgroup and the intention-to-treat study population, which includes both patients with endometrial carcinoma that is pMMR as well as patients whose disease is microsatellite instability-high (MSI-H)/mismatch repair deficient.
Based on an analysis conducted by an independent data monitoring committee, Keytruda plus Lenvima demonstrated a statistically significant and clinically meaningful improvement in OS, PFS and ORR versus chemotherapy (treatment of physician’s choice [TPC] of doxorubicin or paclitaxel).
The safety profile of the Keytruda plus Lenvima combination was consistent with previously reported studies. Merck and Eisai will discuss these data with regulatory authorities worldwide, with the intent to submit marketing authorization applications based on these results, and plan to present these results at an upcoming medical meeting.
KEYNOTE-775/Study 309 is the confirmatory trial for KEYNOTE-146/Study 111, which supported FDA’s 2019 accelerated approval of the Keytruda plus Lenvima combination for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.
This accelerated approval was based on tumor response rate and durability of response and was the first approval granted under Project Orbis. Under Project Orbis, Health Canada and Australia’s Therapeutic Goods Administration granted conditional and provisional approvals, respectively, for this indication.
Merck and Eisai are studying the Keytruda plus Lenvima combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in 13 different tumor types across 20 clinical trials, including a phase III trial evaluating the combination in the first-line setting for patients with advanced endometrial carcinoma (LEAP-001).
