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Merck, known as MSD outside of the United States and Canada, announced that the phase 3 NRG-GY018 trial evaluating Keytruda, Merck’s anti-PD-1 therapy, in combination with standard of care chemotherapy (carboplatin and paclitaxel) met its primary endpoint of progression-free survival (PFS) for the treatment of patients with stage III-IV or recurrent endometrial carcinoma regardless of mismatch repair status. At a pre-specified interim analysis review conducted by an independent Data Monitoring Committee, Keytruda in combination with chemotherapy then continued as single agent every six weeks for up to 14 cycles demonstrated a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy alone in these patients whose endometrial carcinoma was either mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR).
The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and discussed with regulatory authorities.
“Patients with advanced stage or recurrent endometrial cancer, the most common type of gynaecologic cancer in the US, face a poor prognosis with limited treatment options. This is particularly notable in patients who progress after prior platinum-based adjuvant therapy with disease not amenable to curative surgery or radiation,” said Dr. Ramez Eskander, principal investigator and gynecologic oncologist, University of California, San Diego. “In this study, pembrolizumab in combination with carboplatin and paclitaxel resulted in a statistically significant and clinically meaningful improvement in progression-free survival in both the dMMR and pMMR study populations. We look forward to presenting these exciting findings at an upcoming scientific congress.”
“In certain patients with advanced endometrial cancer who have progressed following prior systemic therapy and are not candidates for surgery or radiation, Keytruda has become an important treatment option, both as monotherapy and in combination,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These latest results in the first-line setting are very encouraging and show the potential of Keytruda plus chemotherapy for patients with stage III to IV or recurrent disease regardless of mismatch repair status. We thank our collaborators for their partnership on this study, and we are grateful to the patients and investigators for their participation.”
This trial was sponsored by the US National Cancer Institute (NCI), part of the National Institutes of Health. NRG Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network (NCTN) Groups. Merck provided funding and support through a Cooperative Research and Development Agreement (CRADA) between Merck and NCI.
Merck has a comprehensive clinical development program in endometrial cancer. In the US, Keytruda has two approved indications in endometrial cancer: in combination with Lenvima (lenvatinib), for the treatment of patients with advanced endometrial carcinoma that is pMMR, as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; and as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Additionally, Merck is evaluating Keytruda in first-line advanced endometrial cancer both as monotherapy (KEYNOTE-C93/ENGOT-en15/GOG-3064) and in combination with Lenvima (LEAP-001/ENGOT-en9), as well as in the adjuvant setting (KEYNOTE-B21/ENGOT-en11/GOG-3053).
NRG-GY018 is a randomized, blinded, placebo-controlled phase 3 trial (ClinicalTrials.gov, NCT03914612) evaluating Keytruda in combination with standard of care chemotherapy (paclitaxel and carboplatin) versus placebo plus standard of care chemotherapy alone for the treatment of measurable stage III, IVA, IVB or recurrent endometrial cancer in pMMR and dMMR cohorts. The primary endpoint is PFS, and secondary endpoints include overall survival, objective response rate, duration of response and safety. The trial enrolled 819 patients who were randomized to receive Keytruda plus chemotherapy every three weeks for approximately six cycles followed by Keytruda as a single agent every six weeks for up to 14 cycles, or placebo plus chemotherapy. Enrolled patients were required to have MMR testing prior to randomization; approximately 70% of patients were pMMR, and approximately 30% were dMMR.
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. This disease remains the only gynaecologic malignancy with a rising incidence and mortality. In the US, it is estimated there will be approximately 66,000 new cases of uterine body cancer and approximately 13,000 deaths from the disease in 2023. Globally, endometrial cancer is the sixth most common cancer in women and 15th most common cancer overall.
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 tumour 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 tumour cells and healthy cells.
Merck has the industry’s largest 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 programme 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.
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