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KEYTRUDA® (pembrolizumab) plus concurrent chemoradiotherapy demonstrated statistically significant and clinically meaningful improvement in PFS versus concurrent chemoradiotherapy alone in these patients
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with external beam radiotherapy (EBRT) plus concurrent chemotherapy, followed by brachytherapy (also known as concurrent chemoradiotherapy) met one of its primary endpoints of progression-free survival (PFS) as treatment for newly diagnosed patients with high-risk locally advanced cervical cancer. At a prespecified interim analysis conducted by an independent Data Monitoring Committee, KEYTRUDA in combination with concurrent chemoradiotherapy showed a statistically significant and clinically meaningful improvement in PFS versus concurrent chemoradiotherapy alone.
A favorable trend in overall survival (OS), the trial’s other primary endpoint, was also observed for KEYTRUDA plus concurrent chemoradiotherapy compared to concurrent chemoradiotherapy alone; however, these OS data were not mature at the time of this interim analysis. The trial is continuing and follow-up of OS is ongoing. 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 will be submitted to regulatory authorities.
“The role of KEYTRUDA is already established in certain patients with persistent, recurrent or metastatic cervical cancer, and these results reinforce our research efforts in earlier stages of disease where there is a greater potential for better outcomes,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “We are encouraged by these results that show treatment with KEYTRUDA significantly improved progression-free survival for patients with newly diagnosed high-risk locally advanced cervical cancer. We thank the patients, investigators and our partners at ENGOT and GOG for their important contributions to this study and look forward to sharing these results with the medical community.”
“Patients with high-risk locally advanced cervical cancer often have a poor prognosis, with more than half of patients experiencing disease recurrence within two years. However, there have been limited new treatment advances for these patients beyond the current standard of care in the last 20 years,” said Prof. Domenica Lorusso, the study’s overall principal investigator, lead investigator for ENGOT, and associate professor of Obstetrics and Gynecology at the Catholic University of Rome. “These results are very encouraging and support the use of pembrolizumab combined with the current standard of care in locally advanced cervical cancer to help address the need for new treatment options beyond chemoradiotherapy alone.”
In the U.S., KEYTRUDA has two approved indications in cervical cancer: in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test; and as a single agent, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
About KEYNOTE-A18/ENGOT-cx11/GOG-3047 KEYNOTE-A18, also known as ENGOT-cx11/GOG-3047, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04221945) sponsored by Merck and conducted in collaboration with the European Network for Gynaecological Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG) evaluating KEYTRUDA in combination with EBRT plus concurrent chemotherapy (cisplatin), followed by brachytherapy (also known as concurrent chemoradiotherapy) compared to placebo plus concurrent chemoradiotherapy for the treatment of newly diagnosed high-risk (stage 1B2-2B with lymph node-positive disease, and stage 3-4A with and without lymph node-positive disease) locally advanced cervical cancer where patients are treated with definitive intent. The primary endpoints are PFS and OS, and secondary endpoints include complete response (CR) rate, objective response rate (ORR) and safety. The trial enrolled 1,060 patients who were randomized to receive:
About cervical cancer Cervical cancer forms in a lower part of the uterus, in cells lining the cervix. All women are at risk for cervical cancer. It is most frequently diagnosed between the ages of 35 to 44. Cervical cancer is the fourth most common cancer in women globally. In the U.S., it is estimated there will be approximately 14,000 new cases of invasive cervical cancer and about 4,000 women will die from cervical cancer in 2023. More than nine out of 10 cervical cancers have been associated with the human papillomavirus (HPV), a common virus that most sexually active people get at some point in their lives. For most people, HPV clears on its own; but for the very few who don’t clear the virus, HPV can lead to cervical cancer later in life. There is no way to know which people who have HPV will develop cancer. A critically important step is having regular cervical cancer screenings and talking with an HCP about prevention.
About Merck’s research in breast and gynecologic cancers Merck has a comprehensive clinical development program in breast and gynecological (ovarian, cervical, and endometrial) cancers, comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of these cancers as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck’s early-stage cancer clinical program Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with more than 25 ongoing Phase 3 studies across multiple types of cancer.
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 1,600 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 KEYTRUDA® (pembrolizumab) Indications in the U.S.Cervical Cancer KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Selected Important 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 PD-1 or the 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 (
