On July 19, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported 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 (Press release, Merck & Co, JUL 19, 2023, View Source [SID1234633317]). 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.
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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:
KEYTRUDA (200 mg intravenously [IV]) on Day one of each three-week cycle (Q3W) for five cycles followed by KEYTRUDA 400 mg IV on Day one of each six-week cycle (Q6W) for an additional 15 cycles plus concurrent chemoradiotherapy (cisplatin 40mg/m^2 IV once per week [QW] for five or six weeks plus EBRT followed by brachytherapy with minimum total radiotherapy dose of 90 Gray Units [Gy] for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days [with an extension to a maximum of 56 days for unforeseen delays]); or
Placebo plus concurrent chemoradiotherapy (cisplatin 40mg/m^2 IV QW for five or six weeks plus EBRT followed by brachytherapy with minimum total radiotherapy dose of 90 Gy for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days [with an extension to a maximum of 56 days for unforeseen delays]).
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.