Merck, known as MSD outside the US and Canada, announced today that the US Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as a single agent for the treatment of patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) as determined by an FDA-approved test, who have disease progression after prior systemic therapy in any setting and are not.
The approval is based on fresh results from the KEYNOTE-158 trial’s Cohorts D and K. At a median follow-up period of 16.0 months, the objective response rate (ORR) for patients who received KEYTRUDA was 46 percent (95 percent CI, 35-56) with a complete response rate of 12 percent and a partial response rate of 33 percent (range, 0.5 to 62.1 months). 68 percent of the patients who responded (n=41) had responses that lasted 12 months or longer, and 44 percent had responses that lasted 24 months or longer. The median duration of response (DOR) (range: 2.9 to 55.7+ months) was not met.
“New data from the KEYNOTE-158 trial showed an objective response rate of 46% for certain patients with advanced endometrial carcinoma that is MSI-H or dMMR treated with KEYTRUDA. The objective response rate and duration of response observed in this trial solidify the role of KEYTRUDA as a treatment option for these patients,”said Dr. David O’Malley, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center.
Immune-mediated adverse reactions, which can be severe or fatal, can affect any organ system or tissue, and they can affect many body systems at the same time. Pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic responses, solid organ transplant rejection, and problems of allogeneic hematopoietic stem cell transplantation are all immune-mediated adverse effects that can develop during or after treatment with KEYTRUDA
The list of important immune-mediated adverse reactions may not cover all serious and deadly immune-mediated adverse events. To ensure the safe administration of KEYTRUDA, it is critical to identify and address immune-mediated adverse events as soon as possible. KEYTRUDA should be withheld or permanently discontinued, and corticosteroids should be supplied if necessary, depending on the severity of the adverse response. Infusion-related responses to KEYTRUDA might be serious or life-threatening. When given to a pregnant woman, KEYTRUDA has the potential to harm the foetus due to its mechanism of action. See “Selected Important Safety Information” below for more information.
“This FDA approval is great news for women facing advanced endometrial cancer. We have seen substantial progress in delivering treatment options for patients with advanced endometrial cancer with KEYTRUDA, as monotherapy and in combination, with two approved indications in this area. We remain committed to pursuing meaningful advances in gynecologic and breast cancers through our portfolio of medicines,”said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories.
This is KEYTRUDA’s second indication of endometrial cancer. Patients with advanced endometrial cancer that is neither MSI-H nor dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation, can use KEYTRUDA in combination with LENVIMA (lenvatinib). Merck is aggressively expanding its gynecologic and breast cancer portfolios, with an extensive clinical development program for KEYTRUDA and numerous additional experimental and authorized treatments in these areas.
Adverse reactions, some of which can be serious or fatal, may occur with LENVIMA, including hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw, and embryo-fetal toxicity.
When administered to a pregnant woman, LENVIMA can cause foetal damage based on its mechanism of action and findings from animal reproduction studies. Females who are sexually active should be encouraged to utilise effective contraception. LENVIMA should be stopped, decreased, or terminated depending on the severity of the adverse response. Additional Selected Safety Information about LENVIMA can be found below.