Merck (NYSE: MRK), known as MSD outside the U.S. and Canada, has announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate. This combination is proposed for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.
This recommendation is based on the first interim analysis of the Phase 3 KEYNOTE-A39 trial (also known as EV-302), conducted in collaboration with Pfizer (formerly Seagen) and Astellas. The trial demonstrated that the combination of KEYTRUDA and enfortumab vedotin resulted in statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared to platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin). Specifically, the KEYTRUDA-enfortumab vedotin combination reduced the risk of death by 53% (HR=0.47 [95% CI, 0.38-0.58]; p<0.0001) compared to platinum-based chemotherapy, with 30% of patients experiencing events versus 51% in the chemotherapy group. Additionally, this combination reduced the risk of disease progression or death by 55% (HR=0.45 [95% CI, 0.38-0.54]; p<0.0001), with 50% of patients experiencing events compared to 69% in the chemotherapy group. The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the EU, with a final decision anticipated in the third quarter of 2024.
Dr. Eliav Barr, Senior Vice President and Head of Global Clinical Development at Merck Research Laboratories, commented, “The CHMP’s positive opinion reinforces the landmark results from KEYNOTE-A39 and aligns with recent clinical guidelines from the European Society for Medical Oncology and the European Association of Urology, which recommend KEYTRUDA plus enfortumab vedotin as the preferred first-line treatment for advanced or metastatic urothelial carcinoma, regardless of platinum eligibility. We eagerly await the European Commission’s decision and are excited about the prospect of establishing a new standard of care for patients in the EU.”
If approved, this will be KEYTRUDA’s third indication for bladder cancer in the EU. It was previously approved in the EU as a monotherapy for adults with locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy or who are ineligible for cisplatin-based chemotherapy, based on results from the KEYNOTE-045 and KEYNOTE-052 trials, respectively. In December 2023, KEYTRUDA plus enfortumab vedotin was also approved in the U.S. for treating adults with locally advanced or metastatic urothelial carcinoma.
Merck, in collaboration with Pfizer and Astellas, is further investigating this combination across multiple stages of urothelial cancer, including two Phase 3 trials in muscle-invasive bladder cancer: 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-PD-1 therapy that enhances the immune system’s ability to detect and combat tumor cells. As a humanized monoclonal antibody, KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may target both tumor and healthy cells.
Merck boasts the industry’s largest immuno-oncology clinical research program, with over 1,600 trials exploring KEYTRUDA across various cancers and treatment settings. This extensive clinical program aims to elucidate the role of KEYTRUDA in different cancers and identify factors that may predict patient benefit from the treatment, including exploring various biomarkers.
