Merck (NYSE: MRK), known as MSD outside of the United States and Canada, has announced the successful outcome of the Phase 3 KEYNOTE-A18 trial, also recognized as ENGOT-cx11/GOG-3047. This trial assessed KEYTRUDA, Merck’s anti-PD-1 therapy, combined with chemoradiotherapy (CRT) for treating newly diagnosed patients with high-risk locally advanced cervical cancer.
At a predetermined interim analysis conducted by an independent Data Monitoring Committee, the combination of KEYTRUDA with concurrent CRT demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to concurrent CRT alone. The safety profile observed for KEYTRUDA in this trial remained consistent with previous reports, with no identification of new safety signals. Detailed results from the trial will be presented at an upcoming medical conference and shared with regulatory authorities globally.
This achievement follows the fulfillment of another primary endpoint of the KEYNOTE-A18 trial, progression-free survival (PFS), in 2023. These PFS results, presented at the European Society for Medical Oncology (ESMO) Congress 2023, contributed to the approval of KEYTRUDA in combination with CRT by the U.S. Food and Drug Administration (FDA) for treating patients with FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA cervical cancer in January 2024.
Dr. Gursel Aktan, Vice President of Global Clinical Development at Merck Research Laboratories, highlighted the significance of this milestone, emphasizing that it marks the first Phase 3 trial where an immunotherapy-based regimen has exhibited a substantial improvement in overall survival compared to chemoradiotherapy alone. These results reinforce Merck’s commitment to exploring KEYTRUDA’s potential across various cancer types, particularly in earlier disease stages, with the aim of achieving better outcomes.
Prof. Domenica Lorusso, the study’s principal investigator and professor of Obstetrics and Gynecology at Humanitas University, emphasized the importance of these findings for both patients and the medical community. The success of this regimen in extending the lives of patients with locally advanced cervical cancer underscores the significance of the KEYNOTE-A18 trial data.
In the United States, KEYTRUDA has two additional approved indications for cervical cancer. It is approved in combination with chemotherapy, with or without bevacizumab, for treating patients with persistent, recurrent, or metastatic cervical cancer expressing PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved test. Additionally, it is approved as a single agent for treating patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy and expressing PD-L1 (CPS ≥1).
The KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, is a randomized, double-blind Phase 3 trial sponsored by Merck in collaboration with ENGOT groups and the GOG Foundation, Inc. It investigates KEYTRUDA in combination with CRT compared to placebo plus concurrent CRT for treating newly diagnosed high-risk locally advanced cervical cancer. The trial enrolled 1,060 patients with cervical cancer and evaluated various endpoints, including PFS, OS, complete response rate, objective response rate, and safety.
Cervical cancer, affecting the cells lining the cervix, is a significant health concern globally. Despite advancements in screening and prevention, it remains a prevalent cancer, particularly among women aged 35 to 44. Merck’s dedication to advancing research in breast and gynecologic cancers includes a robust clinical development program focusing on KEYTRUDA, with ongoing Phase 3 studies evaluating its efficacy as monotherapy and in combination therapies.
KEYTRUDA® (pembrolizumab) injection, 100 mg, is an anti-programmed death receptor-1 (PD-1) therapy that enhances the body’s immune system’s ability to detect and combat tumor cells. It works by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, activating T lymphocytes that may target tumor cells and healthy cells.
Merck’s immuno-oncology clinical research program for KEYTRUDA comprises over 1,600 trials across various cancers and treatment settings. The program aims to understand KEYTRUDA’s role in cancer treatment and identify factors predicting patients’ likelihood of benefiting from KEYTRUDA therapy.
This success underscores Merck’s commitment to advancing cancer treatment options and improving outcomes for patients affected by cervical cancer and other malignancies.
