Pembrolizumab plus enfortumab vedotin in bladder cancer

New data presented during the last ESMO congress showed that pembrolizumab plus the antibody-drug conjugate enfortumab vedotin reduced the risk of death versus chemotherapy by 53% in patients with previously untreated locally advanced or metastatic urothelial carcinoma, with a median overall survival improvement by more than 15 months versus chemoteherapy.
The EV-302 clinical trial (also known as KEYNOTE-A39) is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer. The study enrolled 886 patients who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status; they were randomized to receive either enfortumab vedotin in combination with pembrolizumab or chemotherapy. Patients treated with enfortumab vedotin and pembrolizumab had a median overall survival of 31.5 months compared to 16.1 months in the chemotherapy arm and a median progression-free survival of 12.5 months compared to 6.3 months, respectively, thus reducing the risk of disease progression or death by 55%. Results were consistent across all predefined subgroups, including patients who may or may not be eligible for treatment with cisplatin-based chemotherapy, patients whose tumors expressed both high or low levels of PD-L1, and patients with or without liver metastases. The safety profile for pembrolizumab plus enfortumab vedotin was consistent with results observed in the Phase 1/2 KEYNOTE-869/EV-103 trial. The phase 3 KEYNOTE-A39 trial is intended to serve as the basis for global regulatory submissions and as the confirmatory trial for the current U.S. accelerated approval of pembrolizumab plus enfortumab vedotin as first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible to receive cisplatin-containing chemotherapy. «These results, showing a 53% reduction in the risk of death for the combination compared to chemotherapy, are striking and may open a new chapter for the treatment of these patients diagnosed with advanced urothelial carcinoma, who face an urgent need for new therapies», said Thomas Powles, KEYNOTE-A39 primary investigator and director of Barts Cancer Center presenting these data during a Presidential Symposium at the ESMO Congress 2023.