Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate, for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.

The recommendation is based on results from the first interim analysis of the Phase 3 KEYNOTE-A39 trial (also known as EV-302), which was conducted in a research collaboration with Pfizer (previously Seagen) and Astellas, in which KEYTRUDA plus enfortumab vedotin demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) versus platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin). In KEYNOTE-A39, the KEYTRUDA plus enfortumab vedotin combination reduced the risk of death by 53% (HR=0.47 [95% CI, 0.38-0.58]; p<0.0001) versus platinum-based chemotherapy (with 133/442 [30%] vs 226/444 [51%] events observed, respectively), with the combination also reducing the risk of disease progression or death by 55% (HR=0.45 [95% CI, 0.38-0.54]; p<0.0001) versus platinum-based chemotherapy (with 223/442 [50%] vs 307/444 [69%] events observed, respectively). The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union (EU), and a final decision is expected in the third quarter of 2024.

“The CHMP’s positive opinion reinforces the landmark results from KEYNOTE-A39 and follows the recent adoption of the European Society for Medical Oncology and European Association of Urology clinical guidelines recommending KEYTRUDA plus enfortumab vedotin as the preferred first-line treatment for patients with advanced or metastatic urothelial carcinoma, regardless of platinum eligibility,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We look forward to the European Commission’s decision and are excited to be taking the first steps to provide a potential new first-line standard of care for the treatment of this disease in patients in the EU.”

If approved, this will be the third bladder cancer indication for KEYTRUDA in the EU. KEYTRUDA was previously approved in the EU as monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy, as well as adults who are not eligible for cisplatin-containing chemotherapy, based on results from KEYNOTE-045 and KEYNOTE-052, respectively. In December 2023, KEYTRUDA plus enfortumab vedotin was approved in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

Merck, in collaboration with Pfizer and Astellas, are evaluating this combination as part of an extensive clinical development program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in muscle-invasive bladder cancer in KEYNOTE-B15 (NCT04700124, also known as EV-304) and KEYNOTE-905 (NCT03924895, also known as EV-303).

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.