Enfortumab Vedotin Study Positive in Locally Advanced or Metastatic Urothelial Carcinoma

The global phase 3 EV-301 study (NCT03474107) of enfortumab vedotin-ejfv (Padcev) in adult patients with locally advanced or metastatic urothelial carcinoma who received prior platinum-based chemotherapy and a PD-1/PD-L1 inhibitor met its primary end point of overall survival (OS) compared with chemotherapy, announced Seattle Genetics, Inc., in a press release.

The study showed a significant improvement in OS with a 30% reduction in the risk of death (HR, 0.70; 95% CI, 0.56-0.89; P =.001). There was also a significant improvement in progression-free survival (PFS), which was a secondary end point in the study, with a 39% reduction in risk of disease progression or death (HR, 0.61; 95% CI, 0.50-0.75; P <.00001).

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

The adverse events (AEs) observed in the enfortumab vedotin were consistent with those listed in the United States Prescribing Information. The most common grade 3 or greater AEs occurring in at least 5% of patients included rash, hyperglycemia, decreased neutrophil count, fatigue, anemia, and decreased appetite.

Patients enrolled to the chemotherapy arm of the study will be allowed the opportunity to receive enfortumab vedotin.

Seattle Genetics plans to submit these data for presentation at an upcoming medical meeting. The data will also be submitted to the FDA as the confirmatory study following the accelerated approval of this agent in 2019. The study is also expected to support global registrations as well.

“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,” said Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head, Astellas, in a statement. “We look forward to discussing these results with global health authorities.”

The multicenter, open-label, randomized study aimed to evaluate enfortumab vedotin compared with physician’s choice of chemotherapy, which included either docetaxel, paclitaxel, or vinflunine, in approximately 600 patients with locally advanced or metastatic urothelial carcinoma who had been previously treated with a PD-1/PD-L1 inhibitor and platinum-based chemotherapy. Other secondary end points of the study induced duration of response, overall response rate, safety/tolerability, and quality of life.

To be included in the study, patients had to have a histologically or cytologically confirmed urothelial carcinoma with radiographic progression or relapse during or after an immune checkpoint inhibitor for locally advanced or metastatic disease. They had to have received a prior platinum-containing regimen in the neoadjuvant or adjuvant setting, and they also had to have radiologically documented metastatic or locally advanced disease at baseline, and an ECOG performance status of either 0 or 1.

Patients were excluded from the study if they had preexisting sensory or motor neuropathy grade ≥ 2, active central nervous system metastases, or ongoing clinically significant toxicity associated with prior therapy. They were also ineligible to enroll if they had prior treatment with enfortumab vedotin or another monomethyl auristatin E-based antibody–drug conjugate, more than 1 prior chemotherapy regimen for locally advanced or metastatic urothelial cancer, or prior chemotherapy for urothelial cancer with all available study therapies in the control arm.

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_{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. Seattle Genetics. September 18, 2020. Accessed September 18, 2020. https://bwnews.pr/3mBrTOj}