Seagen Inc., and Astellas Pharma Inc., report that both primary end points of the phase 3 EV-302 clinical trial have been met.
The use of enfortumab vedotin-ejfv (Padcev) combined with pembrolizumab (Keytruda) vs chemotherapy for the treatment of patients with previously untreated locally advanced or metastatic urothelial cancer (mUC) led to significant improvements in the dual primary end points of overall survival (OS) and progression-free survival (PFS).1
These findings come from the topline analysis of the phase 3 EV-302 clinical trial (NCT04223856), which was assessed by an Independent Data Monitoring Committee (IDMC). According to the IDMC, the prespecified boundary for OS improvement was crossed at the interim analysis. Further, the safety profile of enfortumab vedotin plus pembrolizumab in the study was consistent with previous reports in patients with previously untreated, locally advanced mUC.
“Over 200,000 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,” said Thomas Powles, MRCP, MD, professor of genitourinary oncology at Queen Mary University of London; director, Barts Cancer Center, in a press release.
EV-302 is an open-label, randomized, controlled, phase 3 study. It is serving as the confirmatory trial for the accelerated approval of enfortumab vedotin plus pembrolizumab for the treatment of adult patients with previously untreated, locally advanced mUC who are not eligible to receive cisplatin-containing chemotherapy.
The accelerated approval of enfortumab vedotin combined with pembrolizumab was granted based on results from the phase 1b/2 EV-103 trial (NCT03288545; KEYNOTE-869). In EV-103, enfortumab vedotin plus pembrolizumab achieved a 73.3% response rate, and a 64.5% confirmed overall response rate (ORR), according to results from 149 patients. The median duration of response (DOR) was not reached. In addition, a 45.2% confirmed ORR was observed with enfortumab vedotin alone, along with a 13.2-month DOR.2
Continued study of the combination in EV-302 will include an investigation of the study’s secondary end point, which includes ORR, time to pain progression, mean change from baseline in worst pain at week 26, duration of PFS, DOR, disease control rate, change from baseline in patient-reported outcome (PRO) assessment, mean score in PRO assessment, incidence of adverse events (AEs), incidence of laboratory abnormalities, and treatment discontinuation rate due to AEs.3
All patients in the study had histologically documented disease, measurable disease, and had not received prior systemic therapy for locally advanced or mUC. Patients were required to be eligible for treatment with cisplatin- or carboplatin-containing chemotherapy, archival tissue for biopsy, have an ECOG performance score of 0, 1, or 2, and adequate hematologic and organ function.
“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 a press release.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. News release. Astellas Pharma Inc. September 22, 2023. Accessed September 22, 2023. https://tinyurl.com/4vfkbfs4
2. Hoimes CJ, Flaig TW, Milowsky MI, et al. Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer. J Clin Oncol. 2023;41(1):22-31. doi:10.1200/JCO.22.01643
3. Enfortumab vedotin and pembrolizumab vs. chemotherapy alone in untreated locally advanced or metastatic urothelial cancer (EV-302). ClinicalTrials.gov. Updated August 14, 2023. Accessed September 22, 2023. https://tinyurl.com/mun8r8xx