Padcev-Keytruda Shows Long-Term Efficacy

The results showed a sustained overall survival (OS) and progression-free survival (PFS) benefit consistent with the findings of the primary analysis after an additional 12 months of follow-up (median follow-up of 29.1 months). . These data will be presented during a rapid oral session (Abstract 664) at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) 2025 in San Francisco, CA, on February 14. (at 4:10pm local or PT.)

Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% confidence interval [CI], 0.43-0.61). The median OS was 33.8 months for the combination versus 15.9 months for chemotherapy. The OS benefit was observed in all prespecified subgroups, including cisplatin eligible and ineligible subgroups. Enfortumab vedotin plus pembrolizumab also reduced the risk of disease progression or death by 52% versus chemotherapy (HR = 0.48, 95% CI, 0.41-0.57). The median PFS was 12.5 months for the combination versus 6.3 months for chemotherapy. The safety profile was consistent with previous findings and no new safety concerns were identified.

In addition to longer follow-up data, an exploratory analysis evaluating treatment outcomes and safety profile in patients with confirmed complete response (cCR) will also be presented. Among patients evaluable for response, confirmed objective response rate (cORR) was 67.5% for enfortumab vedotin plus pembrolizumab compared to 44.2% for chemotherapy. Median duration of response (DOR) was 23.3 months (95% CI, 17.8-not estimable [NE]) for the combination and 7.0 months (95% CI, 6.2-9.0) for chemotherapy. A cCR was achieved in 30.4% of patients treated with enfortumab vedotin plus pembrolizumab and 14.5% of patients treated with chemotherapy. Median duration of cCR was not reached for the combination and 15.2 months (95% CI, 10.3-NE) for chemotherapy. In patients with cCR, grade ≥3 treatment-related adverse events occurred in 61.7% of patients in the enfortumab vedotin plus pembrolizumab arm compared to 71.9% in the chemotherapy arm. There were no treatment-related deaths in the cCR subgroup.

The EV-302 trial is an open-label, randomized, controlled Phase III study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.

The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Primary results from the EV-302 study were presented at the European Society for Medical Oncology (ESMO) Congress in October 2023.

Dr. Thomas Powles Professor of Genitourinary Oncology at Queen Mary University of London; Director, Barts Cancer Center, London; EV 302 Primary Investigator said “These latest findings from the EV 302 trial reaffirm the primary results, which demonstrated survival improvements for patients treated with enfortumab vedotin and pembrolizumab that were previously unprecedented in locally advanced or metastatic urothelial cancer. 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.”

Dr. Roger Dansey,  Chief Oncology Officer, Pfizer said: “Patients with bladder cancer can face a poor prognosis, particularly in the advanced stages, and until recently had few available 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.”

 Dr. Ahsan Arozullah, Senior Vice President, Head of Oncology Development, Astellas said: “The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy, which had been the standard of care for first-line locally advanced or metastatic urothelial cancer for decades. We are delighted that the additional follow-up results of the EV 302 trial show a durable benefit. These data represent yet another milestone in our long-standing commitment to helping patients around the world live longer and healthier lives.”“Patients with bladder cancer can face a poor prognosis, particularly in the advanced stages, and until recently had few available 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.”

See citations: Powles T, Valderrama BP et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.  N Engl J Med 2024;390: 875 DOI: 10.1056/NEJMoa2312117 VOL. 390 NO. 10/

 Powels T 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; abstr 664)