Phase 3 EV-301 Trial of Enfortumab Vedotin-ejfv Meets Primary End Point for Urothelial Cancer

September 18, 2020

The clinical trial is comparing enfortumab vedotin-ejfv to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with a platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The phase 3 EV-301 trial of enfortumab vedotin-ejfv (Padcev) met its primary end point of overall survival (OS) compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer, according to Seattle Genetics and Astellas Pharma, the co-developers of the agent.

The clinical trial is comparing enfortumab vedotin-ejfv to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with a platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Following a planned interim analysis, the results of the trial were reviewed by an independent data monitoring committee.

“These survival results from the confirmatory trial for [enfortumab vedotin-ejfv] are welcome news for patients whose cancer has progressed after platinum-based chemotherapy and immunotherapy,” said Roger Dansey, MD, chief medical officer at Seattle Genetics. “We continue to explore [enfortumab vedotin-ejfv’s] activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy.”

The global, multicenter, open-label, randomized phase 3 trial is designed to evaluate enfortumab vedotin-ejfv versus physician's choice of either docetaxel, paclitaxel, or vinflunine in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies. The primary end point is OS of patients treated with enfortumab vedotin-ejfv compared to those treated with chemotherapy. Key secondary end points include progression-free survival (PFS), duration of response, and overall response rate, as well as assessment of safety/tolerability and quality-of-life parameters.

Results from the trial demonstrated that enfortumab vedotin-ejfv significantly improved OS, with a 30% reduction in risk of death (HR, 0.70; 95% CI: 0.56, 0.89; P = .001). Additionally, enfortumab vedotin-ejfv also significantly improved PFS, with a 39% reduction in risk of disease progression or death (HR, 0.61; 95% CI: 0.50, 0.75; P < .00001).

Moreover, for those in the enfortumab vedotin-ejfv arm of the trial, adverse events (AEs) were found to be consistent with those listed in the US prescribing information. The most frequent Grade 3 or higher AEs occurring in more than 5% of patients were rash, hyperglycemia, decreased neutrophil count, fatigue, anemia, and decreased appetite.

Notably, moving forward patients in the chemotherapy arm of the trial will be offered the opportunity to receive enfortumab vedotin-ejfv.

The results from this trial will be submitted to the FDA as the confirmatory trial, following the drug’s accelerated approval in 2019. Further, the trial is also intended to support global registrations.

Data from EV-301 will also be submitted for presentation at an upcoming scientific congress.

“EV-301 is the first randomized trial to show overall survival results compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who previously have received platinum-based treatment and a PD-1 or PD-L1 inhibitor, and we are encouraged by the potential this may have in helping patients who have otherwise limited alternatives,” Andrew Krivoshik, MD, PhD, senior vice president and head of the Oncology Therapeutic Area at Astellas, said in the release. “We look forward to discussing these results with global health authorities.”

Reference:

Seattle Genetics and Astellas Announce PADCEV® (enfortumab vedotin-ejfv) Significantly Improved Overall Survival in Phase 3 Trial in Previously Treated Locally Advanced or Metastatic Urothelial Cancer [news release]. Bothell, Washington and Tokyo. Published September 18, 2020. Accessed September 18, 2020. https://www.businesswire.com/news/home/20200918005101/en/Seattle-Genetics-and-Astellas-Announce-PADCEV%C2%AE-enfortumab-vedotin-ejfv-Significantly-Improved-Overall-Survival-in-Phase-3-Trial-in-Previously-Treated-Locally-Advanced-or-Metastatic-Urothelial-Cancer