Eisai and MSD Announce Publication of Phase 3 KEYNOTE-775/Study 309 Results for Lenvatinib Plus Pembrolizumab in Advanced Endometrial Cancer

On March 10, Eisai and MSD jointly announced that The New England Journal of Medicine (NEJM) recently published the results of the Phase 3 clinical study 309/KEYNOTE-775 trial. This pivotal study evaluated the combination of lenvatinib and pembrolizumab in patients with advanced endometrial cancer who had received a platinum-based chemotherapy regimen in any setting.

Lenvatinib, an orally administered multi-kinase inhibitor developed by Eisai Co., Ltd., inhibits the kinase activity of vascular endothelial growth factor (VEGF) receptors. In addition to normal cell functions, it also inhibits other kinases associated with pathogenic angiogenesis, tumor growth, and cancer progression. According to the press release, lenvatinib as a monotherapy and in combination therapies has been approved in over 70 countries and regions worldwide for indications including thyroid cancer, hepatocellular carcinoma, thymic cancer, renal cell carcinoma, and endometrial cancer. Pembrolizumab, an anti-PD-1 monoclonal antibody from MSD, blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes that may affect both tumor cells and healthy cells. According to the press release, pembrolizumab is currently being evaluated in more than 1,600 clinical trials across various malignant tumors and treatment settings.

In March 2018, Eisai Co., Ltd. and MSD reached a strategic collaboration for the global co-development and co-commercialization of lenvatinib. According to the agreement, lenvatinib can be used as a monotherapy or in combination with pembrolizumab.

The 309/KEYNOTE-775 trial, published in The New England Journal of Medicine, is a multicenter, open-label, randomized, active-controlled phase 3 study conducted in 827 patients with advanced endometrial cancer who had previously received a platinum-based chemotherapy regimen, across any setting (including newly added and added treatments). All patients were randomized 1:1 to receive either the combination of lenvatinib and pembrolizumab or the investigator's choice of treatment, including doxorubicin or paclitaxel.

According to the clinical trial results published earlier by Eisai, compared with chemotherapy, the combination of lenvatinib and pembrolizumab significantly improved overall survival (OS), reducing the risk of death by 38%, while significantly improving progression-free survival (PFS), reducing the risk of disease progression or death by 44%. The median OS in the lenvatinib and pembrolizumab combination treatment group was 18.3 months, compared to 11.4 months in the chemotherapy group; the median PFS in the combination treatment group was 7.2 months, compared to 3.8 months in the chemotherapy group.

According to reports, based on the results of this Phase 3 trial, the combination of lenvatinib and pembrolizumab has been approved in the United States for patients with advanced endometrial cancer that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation. This combination therapy has also been approved in the European Union and Japan for certain patients with advanced or recurrent endometrial cancer, regardless of mismatch repair status. Eisai and MSD are studying the combination in more than 20 clinical trials through the LEAP (lenvatinib and pembrolizumab) clinical program, which involves more than 10 different tumor types.

We look forward to the subsequent approval of more indications for this combination therapy, bringing better treatment options to more cancer patients.

References:

[1] The results of the Phase III Study 309/KEYNOTE-775 trial investigating the combination of Lenvima® and Keytruda® for the treatment of advanced endometrial cancer were published in The New England Journal of Medicine. Retrieved Mar 9, 2022. From https://mp.weixin.qq.com/s/_oakyKvdSiTzd4Y3nO_54g

[2]LENVIMA® (lenvatinib) Plus KEYTRUDA® (pembrolizumab) Significantly Improved Progression-Free Survival and Overall Survival Versus Chemotherapy in Patients With Advanced Endometrial Cancer Following Prior Platinum-Based Chemotherapy in Phase 3 Study. Retrieved Mar 19，2021.From https://www.eisai.com/news/2021/news202116.html

[3] Lenvima® (lenvatinib) in combination with Keytruda® (pembrolizumab) has been approved in Japan for the treatment of patients with unresectable advanced or recurrent endometrial cancer that has progressed after chemotherapy. Retrieved Mar 9, 2022. From https://mp.weixin.qq.com/s/NQd5o7jfk5FH-073PoPOAw

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