Merck announces FDA approval of Keytruda intravenous infusion as a single agent for treatment of advanced endometrial carcinoma

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KENILWORTH, New Jersey , March 21, 2022 (press release) –

 

Based on KEYNOTE-158 Trial, Patients Receiving KEYTRUDA Demonstrated an Objective Response Rate of 46%

Approval Marks Fourth Gynecologic Cancer Indication for KEYTRUDA

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. 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 following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The approval is based on new data from Cohorts D and K of the KEYNOTE-158 trial. The objective response rate (ORR) was 46% (95% CI, 35-56) for patients who received KEYTRUDA, including a complete response rate of 12% and a partial response rate of 33%, at a median follow-up time of 16.0 months (range, 0.5 to 62.1 months). Of the responding patients (n=41), 68% had responses lasting 12 months or longer, and 44% had responses lasting 24 months or longer. Median duration of response (DOR) was not reached (range, 2.9 to 55.7+ months).

“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,” said Dr. David O’Malley, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center. “The objective response rate and duration of response observed in this trial solidify the role of KEYTRUDA as a treatment option for these patients.”

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued, and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.

“This FDA approval is great news for women facing advanced endometrial cancer,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “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.”

This is the second indication for KEYTRUDA in endometrial cancer. KEYTRUDA is also indicated in combination with LENVIMA® (lenvatinib) for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. Merck is rapidly advancing a broad portfolio in gynecologic and breast cancers with an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across 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. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should be advised to use effective contraception. Based on the severity of the adverse reaction, LENVIMA should be interrupted, reduced, and/or discontinued. See below for additional Selected Safety Information for LENVIMA.

About KEYNOTE-158 (Cohorts D and K)

KEYNOTE-158 (ClinicalTrials.gov, NCT02628067) is a multicenter, non-randomized, open-label, multi-cohort trial that enrolled 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma in Cohorts D and K who received at least one dose of KEYTRUDA. Microsatellite instability-high or MMR tumor status was determined using polymerase chain reaction or immunohistochemistry, respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible.

Patients received KEYTRUDA 200 mg intravenously every three weeks until unacceptable toxicity or documented disease progression. Patients treated with KEYTRUDA without disease progression could be treated for up to 24 months. Assessment of tumor status was performed every nine weeks for the first 12 months, and every 12 weeks thereafter. The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

Among the 90 patients with MSI-H or dMMR endometrial carcinoma enrolled in KEYNOTE-158 treated with KEYTRUDA as a single agent, the median duration of exposure to KEYTRUDA was 8.3 months (range, 1 day to 26.9 months). Adverse reactions occurring in patients with endometrial carcinoma were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer treated with KEYTRUDA as a single agent.

About Microsatellite Instability-High

Microsatellite instability (or MSI) is defined by the National Cancer Institute as a change that occurs in the DNA of certain cells, such as cancer cells, in which the number of repeated DNA bases in a microsatellite (a short, repeated sequence of DNA) is different from what it was when the microsatellite was inherited. The cause of MSI may be a defect in the ability to repair mistakes made when DNA is copied in the cell. This defect is also referred to as mismatch repair deficiency (dMMR).

About Endometrial Carcinoma

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 the U.S., it is estimated there will be more than 65,000 new cases of uterine body cancer and more than 12,500 deaths from the disease in 2022. It is estimated that approximately 30% of endometrial carcinomas are MSI‑H or dMMR.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

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 largest immuno-oncology clinical research program. There are currently more than 1,700 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.

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