Pfizer and Astellas Pharma Inc. have announced updated follow-up results from the Phase 3 EV-302 clinical trial (KEYNOTE-A39), evaluating enfortumab vedotin-ejfv, a Nectin-4 directed antibody-drug conjugate, in combination with pembrolizumab, a PD-1 inhibitor, in previously untreated patients with locally advanced or metastatic urothelial cancer. The findings, based on an additional 12 months of follow-up with a median duration of 29.1 months, reaffirm the overall survival and progression-free survival benefit demonstrated in the primary analysis. According to the release, the data will be presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium 2025 in San Francisco.
Thomas Powles, Professor of Genitourinary Oncology at Queen Mary University of London and Primary Investigator of the EV-302 trial, stated that the results confirm the initial findings, highlighting the survival improvements associated with enfortumab vedotin and pembrolizumab. “These data show that the potential survival benefit has become even more robust with extended follow-up and further solidify the combination as standard of care,” he said.
The combination of enfortumab vedotin and pembrolizumab was associated with a 49 per cent reduction in the risk of death compared to chemotherapy, with a hazard ratio of 0.51 and a median overall survival of 33.8 months versus 15.9 months. The overall survival benefit was observed across all prespecified subgroups, including both cisplatin-eligible and cisplatin-ineligible patients. Progression-free survival analysis showed a 52 per cent reduction in the risk of disease progression or death, with a hazard ratio of 0.48 and a median progression-free survival of 12.5 months for the combination compared to 6.3 months for chemotherapy. The safety profile remained consistent with previous findings, with no new safety concerns identified.
An exploratory analysis assessing treatment outcomes and safety in patients with confirmed complete response showed an objective response rate of 67.5 per cent for the combination compared to 44.2 per cent for chemotherapy. Median duration of response was 23.3 months for enfortumab vedotin plus pembrolizumab versus 7.0 months for chemotherapy. A complete response was achieved in 30.4 per cent of patients receiving the combination compared to 14.5 per cent in the chemotherapy group. In patients with a confirmed complete response, grade 3 or higher treatment-related adverse events were reported in 61.7 per cent of those receiving the combination and 71.9 per cent in those receiving chemotherapy, with no treatment-related deaths in this subgroup.
Roger Dansey, Chief Oncology Officer at Pfizer, stated that patients with bladder cancer, particularly in advanced stages, have historically faced poor prognoses with limited treatment options. “The updated EV-302 results show sustained long-term efficacy in a broad population that includes both cisplatin-eligible and ineligible patients and reinforce this combination’s ability to reshape the urothelial cancer treatment landscape,” he said.
Ahsan Arozullah, Senior Vice President and Head of Oncology Development at Astellas, stated that enfortumab vedotin and pembrolizumab provided the first approved alternative to platinum-based chemotherapy in this setting. “We are delighted that the additional follow-up results of the EV-302 trial show a durable benefit,” he said.
Enfortumab vedotin in combination with pembrolizumab is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer in the United States, the European Union, Japan, and other regions. Enfortumab vedotin is also approved as a single agent for patients with previously treated locally advanced or metastatic urothelial cancer who have received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy, or who are ineligible for cisplatin-containing chemotherapy and have received at least one prior line of therapy.