EV-302 Trial Shows ‘Impressive’ Data in Bladder Cancer Responder Population

One of the “striking features” of the updated results from the phase 3 EV-302 trial (NCT04223856) are the “impressive” outcomes among patients who experienced a response to enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda), according to Thomas Powles, MBBS, MRCP, MD.

Powles, a professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew’s Hospital, Queen Mary University of London, in London, United Kingdom, spoke with CancerNetwork^® during the 2025 ASCO Genitourinary Cancer Symposium about exploratory analysis findings from the EV-302 trial. This analysis highlighted outcomes in patients with locally advanced or metastatic urothelial carcinoma who achieved a confirmed complete response (CR) to enfortumab vedotin plus pembrolizumab or chemotherapy.

While disease recurrence was noted in the chemotherapy arm despite early responses, Powles described how durable responses in the enfortumab vedotin arm correlated with improvements in other outcomes such as survival.

The confirmed overall response rate (ORR) was 67.5% (95% CI, 62.9%-71.9%) with enfortumab vedotin plus pembrolizumab vs 44.2% (95% CI, 39.5%-49.0%) with chemotherapy (2-sided P <.00001), which included respective CR rates of 30.4% vs 14.5%. The likelihood of maintaining a CR in each respective arm was 84.3% vs 60.0% at 12 months and 74.3% vs 43.2% at 24 months.

Among those with a confirmed CR, the estimated 24-month progression-free survival rate was 78.2% with enfortumab vedotin plus pembrolizumab compared with 53.7% in the chemotherapy arm (HR, 0.36; 95% CI, 0.21-0.61). Across the confirmed CR subgroup, the estimated 24-month overall survival rates were 95.4% vs 85.8% in each respective arm (HR, 0.37; 95% CI, 0.17-0.80).

Transcript:

Those patients who responded did well, and that’s one of the striking features of this result. What we saw with chemotherapy was many patients initially responding, but the cancer coming back quite quickly. Here, we show durable responses. At 2 years, in [67.5%] of patients who responded to therapy, 50% haven’t progressed at 2 years. That’s really impressive. Then, of course, the second piece around the patients [with CRs is] that of 30% who had a CR, 95% of those patients were alive at 2 years. That’s, in my opinion and others, transformative compared to what we saw previously.

Reference

Powles TB, Van der Heijden MS, Loriot Y, et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol. 2025;43(suppl 5):664. doi:10.1200/JCO.2025.43.5_suppl.664