The frontline combination of enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) induced a response in nearly two-thirds of patients with unresectable locally advanced or metastatic urothelial cancer who are ineligible to receive cisplatin-based chemotherapy, according to topline results from the phase 1b/2 EV-103 (KEYNOTE-869) clinical trial.1
Per the assessment of a blinded independent panel, the combination led to a confirmed objective response rate of 64.5%. The median duration of response had not yet been reached.
Overall, the ongoing, multicohort, open-label, multicenter EV-103 trial (NCT03288545) is evaluating enfortumab vedotin alone and with different combinations of anticancer therapies as a first- and second-line treatment for patients with locally advanced or metastatic urothelial cancer.
The topline results announced today are from study cohort K, in which patients are being randomized to either monotherapy with enfortumab vedotin (n = 73) or combination therapy with enfortumab vedotin plus pembrolizumab (n = 76).
Regarding safety in cohort K, treatment-emergent adverse events grade ≥3 that occurred in at least 5% of patients were rash maculo-papular, anemia, lipase increased, urinary tract infection, hyperglycemia, fatigue, neutropenia, hematuria, diarrhea, acute kidney injury, hyponatremia, chronic kidney disease, weight decreased, syncope, hypophosphatemia, pneumonitis, sepsis, and alanine aminotransferase increased.
"We are encouraged by the positive topline results of Cohort K for the combination of enfortumab vedotin and pembrolizumab in first-line locally advanced or metastatic urothelial cancer, and we look forward to sharing results at an upcoming medical meeting," Roger Dansey, MD, interim CEO and chief medical officer, Seagen, stated in a press release.
Based on prior results from the EV-103 trial, the FDA granted a breakthrough therapy designation to enfortumab vedotin plus pembrolizumab as a first-line treatment for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy.
The designation, which will expedite the development and regulatory review of the combination in this setting, was based on findings from the dose-escalation and dose-expansion cohort A of the EV-103 trial,2 which enrolled patients with locally advanced or metastatic urothelial cancer who were not eligible for cisplatin-based chemotherapy.
1. Astellas and Seagen Announce Positive Topline Results For PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) as First-Line Treatment for Advanced Urothelial Cancer. Published online July 26, 2022. Accessed July 26, 2022. https://prn.to/3z0ZPuU
2. Rosenberg JE, Flaig TW, Friedlander TW, et al. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2020;38(suppl; abstr 441)