KEYTRUDA (pembrolizumab) as Monotherapy Reduced the Risk of Disease Progression or Death by 43% for Certain Patients With Advanced or Recurrent Endometrial Cancer With Mismatch Repair Deficient (dMMR) Tumors Compared to Chemotherapy

KEYNOTE-C93 showed median progression-free survival (PFS) was more than four times longer for these patients treated with KEYTRUDA as monotherapy (38.2 months) compared to platinum doublet chemotherapy (8.4 months)

KEYNOTE-C93 is the first Phase 3 trial of a PD-1 inhibitor to show a statistically significant and clinically meaningful improvement in PFS as monotherapy compared to chemotherapy in these patients

Late-breaking results were selected for an official press briefing and will be presented during a Presidential Symposium session at the European Society for Medical Oncology (ESMO) Congress 2026 and published simultaneously in The Lancet

RAHWAY, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from the Phase 3 KEYNOTE‑C93 trial, evaluating KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1 therapy, as monotherapy for the treatment of patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer who had not previously received systemic chemotherapy or who experienced recurrence after receiving prior adjuvant therapy. Results showed KEYTRUDA as monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) for these patients, reducing the risk of disease progression or death by 43% (HR=0.57; [95% CI, 0.42-0.79]; p=0.0002) compared to platinum doublet chemotherapy. These late-breaking results will be presented today during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2026 [Presentation #LBA12], were selected for an official ESMO press briefing and were published simultaneously in The Lancet.

After a median follow-up of 36.7 months (range, 28.4-50.0), median PFS was 38.2 months (95% CI, 17.9-NR) for KEYTRUDA versus 8.4 months (95% CI, 6.8-10.4) for chemotherapy, with 36-month PFS rates of 52.8% (95% CI, 44.2-60.7) versus 30.0% (95% CI, 22.4-37.9), respectively. In addition to an improvement in PFS, a favorable trend in overall survival (OS), the trial’s other primary endpoint, was observed for KEYTRUDA monotherapy versus platinum doublet chemotherapy (HR=0.77 [95% CI, 0.52-1.15]; p=0.1000). Median OS was not reached (NR) (95% CI, NR-NR) for KEYTRUDA versus NR (95% CI, 38.9-NR) for chemotherapy, with 36-month OS rates of 70.7% (95% CI, 62.4-77.5) versus 62.0% (95% CI, 53.1-69.8), respectively. The trial is continuing, and follow-up of OS is ongoing. Results will be shared with regulatory authorities worldwide.

“These results highlight the potential of a chemotherapy-free approach for certain patients with dMMR advanced or recurrent endometrial cancer, with pembrolizumab monotherapy demonstrating a clinically meaningful benefit in progression-free survival compared to chemotherapy,” said Dr. Brian Slomovitz, director of Gynecologic Oncology and deputy director of the Braman Comprehensive Cancer Center at Mount Sinai Medical Center in Miami Beach, Florida, and the study’s overall principal investigator. “After years of platinum-based chemotherapy serving as the frontline standard, these findings could help provide an additional treatment option beyond carboplatin plus paclitaxel in combination with KEYTRUDA for these patients.”

“KEYTRUDA is already part of an established treatment regimen with platinum doublet chemotherapy for patients with primary advanced or recurrent endometrial cancer regardless of mismatch repair status, and we’re excited by these results showing its further potential as a monotherapy option for appropriate patients whose tumors are dMMR,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “As incidence rates of endometrial cancer continue to rise, we remain committed to advancing new potential treatment options for women facing this disease.”

Confirmed objective response rate (ORR), a key secondary endpoint, was 64.1% (95% CI, 55.8-71.9) with KEYTRUDA versus 62.1% (95% CI, 53.6-70.0) with chemotherapy; complete response rates were 33.8% and 26.2%, respectively. ORR was not tested for statistical significance at this analysis. Among responders, median duration of response (DOR) was not reached for patients receiving KEYTRUDA versus 10.2 months for patients receiving chemotherapy; the 24-month DOR rate was 77.0% versus 41.3%, and the 36-month DOR rate was 70.7% versus 40.0%, respectively.

The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies, and no new safety signals were identified in either treatment arm. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 18.1% of patients receiving KEYTRUDA (n=149) versus 50.7% of patients receiving chemotherapy (n=144); the most common Grade ≥3 TRAE was anemia, occurring in 2.0% of patients receiving KEYTRUDA compared with 18.1% of patients receiving chemotherapy. Grade ≥3 immune-mediated adverse events and infusion reactions occurred in 7.4% of patients receiving KEYTRUDA and 3.5% of patients receiving chemotherapy.

In the U.S., KEYTRUDA is the only anti-PD-1 therapy with three approved indications for patients with certain types of endometrial cancer. KEYTRUDA is indicated:

• In combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma;
• In combination with LENVIMA^® (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-authorized 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 adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Merck has a comprehensive clinical development program evaluating KEYTRUDA (both as monotherapy and in combination with chemotherapy) and sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, in endometrial cancer. As previously announced, TroFuse-005 (ClinicalTrials.gov, NCT06132958), evaluating sac-TMT, met its primary endpoints of PFS and OS, as well as its key secondary endpoint of ORR in patients with endometrial cancer who have previously received platinum-based chemotherapy and immunotherapy. These results are also being presented in a Presidential Symposium at ESMO. In addition, TroFuse-033 (NCT06952504) is enrolling patients with pMMR endometrial cancer to evaluate sac-TMT in an earlier treatment setting of first-line maintenance. The KEYNOTE-B21 trial (NCT04634877) evaluating KEYTRUDA remains ongoing for analysis in the dMMR subgroup.

About KEYNOTE-C93

KEYNOTE-C93 is a randomized, open-label Phase 3 trial (NCT05173987) evaluating KEYTRUDA monotherapy versus carboplatin plus paclitaxel in patients with dMMR advanced or recurrent endometrial cancer who have not previously been treated with prior systemic chemotherapy or who experienced recurrence after receiving prior adjuvant therapy. The trial enrolled 299 patients who were randomized to receive either:

• KEYTRUDA (400 mg) intravenously every six weeks for up to 18 cycles, or;
• Combination of paclitaxel (175 mg/m²) and carboplatin (AUC 5 or 6) every three weeks for six cycles.

The trial’s dual primary endpoints are PFS, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and OS. A key secondary endpoint of the study is ORR.

About endometrial cancer

Endometrial cancer (also referred to as 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. More than 90% of uterine body cancers occur in the endometrium. Endometrial cancer is one of the few cancers with increasing mortality. In the U.S., it is estimated there will be approximately 68,270 patients diagnosed with endometrial cancer and approximately 14,450 patient deaths from the disease in 2026. Globally, endometrial cancer is the sixth most common cancer in women and the 15th most common cancer overall.

About Merck’s research in women’s cancers

Merck is advancing research aimed at expanding treatment options for certain breast and gynecologic (ovarian, cervical and endometrial) cancers, with a goal of improving outcomes for more patients affected by these diseases. Breast cancer and gynecologic cancers are the first and second most commonly occurring cancer types among women worldwide, respectively, and Merck aims to provide options to patients facing these devastating diseases. With more than 30 clinical trials in more than 20,000 patients around the world, Merck is driving innovative research to purposefully advance standards of care in women’s cancers. Merck’s research efforts include trials focused on evaluating its medicines in earlier stages, as well as identifying novel mechanisms and new combinations with these treatments. Through our portfolio and pipeline, Merck is working to address the impact of women’s cancers on patients, their families and communities globally.

About KEYTRUDA^® (pembrolizumab) injection for intravenous use, 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 2,800 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.

Selected Indications in the U.S. for KEYTRUDA^® (pembrolizumab)

Endometrial Carcinoma

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

See additional selected indications in the U.S. for KEYTRUDA after the Selected Safety Information.

Selected Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism. The incidence of new or worsening hyperthyroidism was higher in 580 patients with resected NSCLC, occurring in 11% of patients receiving KEYTRUDA as a single agent as adjuvant treatment, including Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening hypothyroidism was higher in 580 patients with resected NSCLC, occurring in 22% of patients receiving KEYTRUDA as a single agent as adjuvant treatment (KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti– PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

Media Contacts:
Julie Cunningham
julie.cunningham@merck.com

Heather Manhardt
heather.manhardt@merck.com

Investor Contacts:
Peter Dannenbaum
(732) 594-1579

Steven Graziano
(732) 594-1583