Merck’s KEYTRUDA® (pembrolizumab) Receives 30th Approval From European Commission With Two New Indications in Gynecologic Cancers

KEYTRUDA plus chemotherapy is the first approval in the EU for an anti-PD-1 therapy combined with chemotherapy only for patients with primary advanced or recurrent endometrial carcinoma regardless of mismatch repair status

KEYTRUDA plus chemoradiotherapy is the first anti-PD-1-based regimen approved in the EU for patients with FIGO 2014 Stage III-IVA locally advanced cervical cancer

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the European Commission (EC) has approved two new indications for KEYTRUDA ® (pembrolizumab), Merck’s anti-PD-1 therapy, in gynecologic cancers. The first approval is for KEYTRUDA, in combination with carboplatin and paclitaxel, for the first-line treatment of primary advanced or recurrent endometrial carcinoma in adults who are candidates for systemic therapy. The second approval is for KEYTRUDA, in combination with chemoradiotherapy (CRT), for the treatment of FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA locally advanced cervical cancer in adults who have not received prior definitive therapy. With these decisions, KEYTRUDA is now approved for 30 indications in the EU, including five in gynecologic cancers – three in endometrial cancer and two in cervical cancer.

“These KEYTRUDA-based regimens have the potential to change the treatment paradigm for people with endometrial and cervical cancer, two of the most commonly diagnosed cancers among women in Europe,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “These approvals underscore the continued expansion of the use of KEYTRUDA in diverse patient populations and treatment settings with utility of KEYTRUDA ranging from earlier lines of therapy to treating advanced disease.”

The EC approvals are based on results from the Phase 3 NRG-GY018 trial, also known as KEYNOTE-868, and the Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, respectively, and follow positive recommendations from the Committee for Medicinal Products for Human Use received in September 2024.

In NRG-GY018/KEYNOTE-868, KEYTRUDA in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy alone.

In KEYNOTE-A18, KEYTRUDA in combination with concurrent CRT demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and PFS compared to concurrent CRT alone for newly diagnosed patients with FIGO 2014 Stage III-IVA locally advanced cervical cancer.

These approvals allow marketing of these KEYTRUDA regimens for these indications in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. Timing for commercial availability of KEYTRUDA for these indications in individual EU countries will depend on multiple factors, including the completion of national reimbursement procedures.

In June 2024, KEYTRUDA in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, was approved in the U.S. for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma based on PFS results from the NRG-GY018 trial. The KEYTRUDA regimen reduced the risk of disease progression or death by 70% (HR=0.30 [95% CI, 0.19-0.48]; p<0.0001) in patients whose cancer was mismatch repair deficient (dMMR) and by 40% (HR=0.60 [95% CI, 0.46-0.78]; p<0.0001) in patients whose cancer was mismatch repair proficient (pMMR) compared to placebo with carboplatin and paclitaxel followed by placebo alone.

In January 2024, KEYTRUDA in combination with CRT was approved in the U.S. for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer based on PFS results from the KEYNOTE-A18 trial. The KEYTRUDA regimen reduced the risk of disease progression or death by 41% (HR=0.59 [95% CI, 0.43-0.82]) versus concurrent CRT alone for these patients.

About NRG-GY018/KEYNOTE-868
NRG-GY018, also known as KEYNOTE-868, is a randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT03914612 ) evaluating KEYTRUDA in combination with standard of care chemotherapy (paclitaxel and carboplatin) versus placebo plus standard of care chemotherapy for the treatment of measurable stage III, IVA, IVB or recurrent endometrial cancer in pMMR and dMMR cohorts. The primary endpoint is PFS, and secondary endpoints include overall survival, objective response rate (ORR), duration of response and safety. The trial enrolled 810 patients who were randomized (1:1) to receive either:

KEYTRUDA (200 mg intravenously [IV]) every three weeks (Q3W) plus paclitaxel (175 mg/m 2 IV) and carboplatin (Area Under Curve [AUC] 5 mg/mL/min IV) for six cycles, followed by KEYTRUDA (400 mg IV) every six weeks (Q6W) for up to 14 cycles; Placebo IV Q3W plus paclitaxel (175 mg/m 2 IV) and carboplatin (AUC 5 mg/mL/min IV) for six cycles, followed by placebo IV Q6W for up to 14 cycles.