EU CHMP Endorses KEYTRUDA and Padcev Combo for Advanced Urothelial Carcinoma

Merck, a pharmaceutical company known as MSD outside of the United States and Canada, has announced a recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for the approval of KEYTRUDA. This anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv), is intended for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. The recommendation is based on data from the Phase 3 KEYNOTE-A39 trial (EV-302), conducted in collaboration with Pfizer (formerly Seagen) and Astellas.

The KEYNOTE-A39 trial showed that the combination of KEYTRUDA and enfortumab vedotin significantly improved overall survival (OS) and progression-free survival (PFS) compared to standard platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin). Specifically, the risk of death was reduced by 53% (HR=0.47) and the risk of disease progression or death was reduced by 55% (HR=0.45) with the combination therapy. These findings highlight the potential of KEYTRUDA plus enfortumab vedotin as a new first-line standard of care for advanced urothelial carcinoma.

Following the CHMP’s positive opinion, the recommendation will be reviewed by the European Commission for marketing authorization in the EU, with a final decision expected in the third quarter of 2024. Dr. Eliav Barr, Merck’s senior vice president and head of global clinical development, expressed optimism about offering a new treatment option to patients in the EU.

If approved, this will be the third indication for KEYTRUDA in treating bladder cancer within the EU. Previously, KEYTRUDA was approved as monotherapy for adults with locally advanced or metastatic urothelial carcinoma who had received prior platinum-containing chemotherapy, and for those not eligible for cisplatin-containing chemotherapy, based on the KEYNOTE-045 and KEYNOTE-052 trials, respectively. Additionally, in December 2023, the combination of KEYTRUDA and enfortumab vedotin was approved in the U.S. for adults with locally advanced or metastatic urothelial cancer.

Merck, alongside Pfizer and Astellas, is undertaking an extensive clinical development program to evaluate this combination therapy across different stages of urothelial cancer. This includes two Phase 3 clinical trials in muscle-invasive bladder cancer, namely KEYNOTE-B15 (EV-304) and KEYNOTE-905 (EV-303).

KEYTRUDA (pembrolizumab) is an anti-PD-1 therapy that enhances the body’s immune system to detect and fight cancer cells. It is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thus activating T lymphocytes that may attack both tumor and healthy cells. Merck’s KEYTRUDA program is currently the largest immuno-oncology clinical research endeavor in the industry, encompassing over 1,600 trials for various cancers and treatment settings.

KEYTRUDA's indications in the U.S. include treatment for adult patients with locally advanced or metastatic urothelial carcinoma, either in combination with enfortumab vedotin or as a monotherapy. It is prescribed for patients who are not eligible for platinum-containing chemotherapy or who have experienced disease progression during or after such chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment. It is also indicated for patients with Bacillus Calmette-Guerin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).

The clinical success of KEYTRUDA, particularly when combined with enfortumab vedotin, underscores its potential to significantly impact the treatment landscape for urothelial carcinoma. The ongoing collaboration and trials aim to further establish its efficacy and broaden its therapeutic applications.