Merck announced the publication of results from the Phase 3 KEYNOTE-775/Study 309 trial in the January 19, 2022 edition of the New England Journal of Medicine. The pivotal study evaluated the combination of KEYTRUDA, Merck's anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, versus chemotherapy (treatment of physician's choice of doxorubicin or paclitaxel) for patients with advanced endometrial carcinoma following at least one prior platinum-based regimen in any setting. The publication includes previously reported data that was first presented in an oral plenary session at the virtual Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women's Cancer.

Results showed that the KEYTRUDA plus LENVIMA combination demonstrated statistically significant improvements in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to chemotherapy. Objective response rate (ORR) data and additional detailed efficacy and safety data, including subgroup analyses, are also featured in the publication. The publication contains results for the all-comer population, including the mismatch repair deficient (dMMR) patient population for which KEYTRUDA plus LENVIMA is not approved in the U.S. Based on the results from the Phase 3 KEYNOTE-775/Study 309 trial, KEYTRUDA plus LENVIMA has been approved in the U.S. for patients with advanced endometrial carcinoma that is not microsatellite instability-high or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

KEYTRUDA plus LENVIMA is also approved in the European Union and Japan for certain patients with advanced or recurrent endometrial carcinoma regardless of mismatch repair status. Merck and Eisai are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in more than 10 different tumor types across more than 20 clinical trials. KEYNOTE-775/Study 309 (ClinicalTrials.gov, NCT03517449) is a Phase 3, multicenter, open-label, randomized, active-controlled study conducted in 827 patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings.

Participants may have received up to two platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade =3 fistula, uncontrolled blood pressure (>150/90 mmHg), significant cardiovascular impairment or event within previous 12 months or patients who had active autoimmune disease or a medical condition that required immunosuppression. The primary efficacy outcome measures were OS and PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors Version (RECIST) v1.1. Secondary efficacy outcome measures included ORR as assessed by BICR.

Patients were randomized 1:1 to receive KEYTRUDA (200 mg intravenously every three weeks) plus LENVIMA (20 mg orally once daily) or investigator's choice, consisting of either doxorubicin (60 mg/m2 every three weeks) or paclitaxel (80 mg/m2 given weekly, three weeks on/one week off). Treatment with KEYTRUDA plus LENVIMA continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for KEYTRUDA, a maximum of 24 months. Administration of KEYTRUDA plus LENVIMA was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated.

Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium and is the most common type of cancer in the uterus. In 2020, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers worldwide (these estimates include both endometrial carcinomas and uterine sarcomas; more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial carcinoma cases and deaths are slightly lower than these estimates). In the U.S., it is estimated there will be nearly 66,000 new cases of uterine body cancer and nearly 13,000 deaths from the disease in 2022.

The five-year relative survival rate for metastatic endometrial carcinoma (stage IV) is estimated to be approximately 17%. KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry's large immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.