Update on KEYTRUDA® Plus Chemo in High-Risk Post-Surgery Endometrial Cancer Phase 3 Trial

A recent clinical trial, Phase 3 KEYNOTE-B21, sponsored by Merck, has concluded that the use of KEYTRUDA, an anti-PD-1 therapy, in combination with chemotherapy and potentially radiotherapy, as an adjuvant treatment for patients with newly diagnosed, high-risk endometrial cancer, did not reach its primary endpoint of disease-free survival (DFS). The trial, which was conducted after surgery with the intention of cure, revealed that the treatment did not meet the pre-specified statistical criteria for DFS when compared to placebo plus chemotherapy, with or without radiotherapy. As a result, the overall survival (OS) was not formally tested due to the lack of superiority in DFS. However, the safety profile of KEYTRUDA remained consistent with previous studies, and no new safety concerns were raised.

Merck is committed to advancing clinical research with KEYTRUDA for endometrial carcinoma, with ongoing trials exploring various combinations and other experimental treatments. The company has two approved indications for endometrial cancer in the U.S., one in combination with LENVIMA® for advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H), and the other as a single agent for advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR).

Merck's extensive clinical development program for endometrial carcinoma includes the NRG-GY018/KEYNOTE-868 trial, which is evaluating KEYTRUDA in combination with standard chemotherapy followed by KEYTRUDA as a single agent for primary advanced or recurrent endometrial carcinoma. The FDA has granted priority review for Merck’s supplemental Biologics License Application (sBLA) based on this study, with a target action date set for June 21, 2024.

Additionally, the KEYNOTE-C93 study is assessing KEYTRUDA against chemotherapy in dMMR advanced or recurrent endometrial carcinoma. There is also the MK-2870-005 study, which is evaluating sacituzumab tirumotecan (sac-TMT), an antibody-drug conjugate (ADC), in comparison to a physician's choice of treatment for endometrial carcinoma patients who have received prior platinum-based chemotherapy and immunotherapy.

Endometrial carcinoma is the most prevalent cancer within the uterus, with an estimated 67,880 new diagnoses and approximately 13,250 deaths expected in the U.S. in 2024. Globally, it ranks as the sixth most common cancer among women and the 15th overall. Post-primary treatment, there is a risk of cancer recurrence, often manifesting as distant metastasis and leading to poorer outcomes.

Merck is dedicated to improving outcomes for patients with breast and gynecologic cancers, with over 20 Phase 3 studies evaluating KEYTRUDA as a monotherapy and in combination with other treatments. The company's research also includes trials exploring KEYTRUDA in earlier stages of cancer and identifying new combinations and formulations with KEYTRUDA.

KEYTRUDA, an anti-PD-1 therapy, works by enhancing the body's immune system to detect and combat tumor cells. It is a humanized monoclonal antibody that inhibits the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thus activating T lymphocytes that can target both tumor and healthy cells. Merck's immuno-oncology clinical research program is the largest in the industry, with over 1,600 trials investigating KEYTRUDA across various cancers and treatment settings. The program aims to understand KEYTRUDA's role in different cancers and identify factors that may predict a patient's response to treatment, including the exploration of several biomarkers.

Selected indications for KEYTRUDA in the U.S. include its use in combination with LENVIMA for advanced endometrial carcinoma that is pMMR or not MSI-H, and as a single agent for advanced endometrial carcinoma that is MSI-H or dMMR. Important safety information for KEYTRUDA highlights the potential for severe and fatal immune-mediated adverse reactions, which can occur in any organ system or tissue and can affect more than one body system simultaneously. Monitoring and management of these reactions are crucial for the safe use of KEYTRUDA.