The EV-302 trial is the confirmatory trial for the FDA’s accelerated approval of pembrolizumab plus enfortumab vedotin for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma.
The combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) improved overall survival (OS) vs chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma, according to topline resultsfrom the phase 3 EV-302 trial (NCT04223856).1
Although specific data are not yet available, Astellas Pharma and Seagen Inc, the co-developers of enfortumab vedotin, reported in a press release that the combination improved both OS and progression-free survival (PFS) compared with chemotherapy in this patient population.
The EV-302 trial is the confirmatory trial for the FDA’s accelerated approval of pembrolizumab plus enfortumab vedotin for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy.2,3 Transitioning an accelerated FDA approval into a full approval requires verification of the treatment’s clinical benefit in a confirmatory trial.
"This study has the potential to be practice changing and offer a new standard of care for first-line metastatic bladder cancer. We look forward to presenting the results at an upcoming medical conference and discussing with regulators in order to get this medicine to patients as soon as possible,” Roger Dansey, MD, president, Research and Development, Seagen, stated in the press release.1
The open-label EV-302 trial enrolled patients with previously untreated locally advanced or metastatic urothelial carcinoma who were eligible for cisplatin- or carboplatin-containing chemotherapy. PD-L1 status did not affect patient eligibility for the study.
Patients were randomized to either the combination or standard of care gemcitabine plus platinum-containing chemotherapy. The co-primary end points were OS and PFS, as measured by blinded independent central review using RECIST criteria (v1.1).
"Over two hundred thousand deaths from urothelial cancer are reported worldwide annually, making it a major cause of morbidity and mortality. The topline results from EV-302 are encouraging for patients with advanced-stage urothelial cancer, which is aggressive and associated with devastating outcomes," EV-302 primary investigator Thomas Powles, MRCP, MD, professor of Genitourinary Oncology at Queen Mary University of London and director of Barts Cancer Center, stated in the press release.1
The accelerated approval of the combination for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy was supported by results from combined dose escalation/cohort A and cohort K of the phase 1b /2 EV-103 trial (KEYNOTE-869; NCT03288545).2,3
The dose escalation cohort and cohort A of EV-103 were single-arm cohorts in which all patients received enfortumab vedotin plus pembrolizumab. Cohort K randomized patients to enfortumab vedotin plus pembrolizumab or enfortumab vedotin alone.
The FDA efficacy analysis included 121 patients from these arms who had been treated with the combination regimen. These patients were systemic therapy–naive in the locally advanced or metastatic setting and were not eligible to receive cisplatin-containing chemotherapy.
The primary efficacy outcome was objective response rate (ORR) by RECIST v1.1 criteria. The ORR in the efficacy population was 68% (95% CI, 58.7-76.0). Of the responders, 12% had a complete response, and 55% of patients had a partial response.2,3
In the dose escalation cohort + cohort A, the median duration of response was 22.1 months (range, 1.0+ to 46.3+). In cohort K the median duration of response was not reached (range, 1.2 to 24.1+).
Also commenting on the EV-302 results in the press release, Ahsan Arozullah, MD, MPH, senior vice president, head of oncology development, Astellas, stated, "We are thrilled that the topline results of the EV-302 study demonstrated that the combination of enfortumab vedotin and pembrolizumab improved the dual primary endpoints of OS and PFS. Patients living with metastatic urothelial cancer are in dire need of additional treatment options and this combination has the potential to advance the standard of care. We are extremely grateful to all of the patients who participated in this trial."1
1. PADCEV® (enfortumab vedotin-ejfv) and KEYTRUDA® (pembrolizumab) Significantly Improve Overall Survival and Progression-Free Survival in Patients With Previously Untreated Advanced Bladder Cancer in Pivotal Phase 3 EV-302 Trial. Published online and accessed September 22, 2023. https://tinyurl.com/2p8mh52h
2. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. Published online and accessed April 3, 2023. https://bit.ly/3MdWuAJ
3. FDA Grants Accelerated Approval for PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Locally Advanced or Metastatic Urothelial Cancer. Published online and accessed April 3, 2023. https://prn.to/3KvpR0n