Merck, known as MSD outside of the United States and Canada, announced that the European Commission (EC) has approved KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate, for the first-line treatment of unresectable or metastatic urothelial carcinoma in adults. The decision follows the adoption of the European Society for Medical Oncology and European Association of Urology clinical guidelines recommending the combination as the preferred first-line treatment for these patients, regardless of platinum eligibility.
This approval by the EC also follows the positive recommendation from the Committee for Medicinal Products for Human Use received in July 2024 , which was 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 KEYNOTE-A39, 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).
At a median follow-up of 17.3 months (range, 0.3 to 37.2 months), the KEYTRUDA plus enfortumab vedotin combination reduced the risk of death by 53% (HR=0.47 [95% CI, 0.38-0.58]; p<0.00001) 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<0.00001) versus platinum-based chemotherapy (with 223/442 [50%] vs. 307/444 [69%] events observed, respectively).
“For the first time in decades, adult patients with unresectable or metastatic urothelial carcinoma have the option of a potential new first-line standard of care that may help extend their lives,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We are pleased with the European Commission’s decision, and we look forward to being able to provide KEYTRUDA as part of this novel treatment regimen for this devastating disease to patients in the European Union.”
This approval allows marketing of KEYTRUDA in combination with enfortumab vedotin for this indication in all 27 European Union (EU) member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. KEYTRUDA is now approved for three indications in bladder cancer, and for 28 indications overall 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 and whose tumors express PD-L1 with a combined positive score (CPS) ≥10, based on results from KEYNOTE-045 and KEYNOTE-052, respectively. In December 2023 , KEYTRUDA in combination with 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, is 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).