FDA Approves Enfortumab Vedotin-Ejfv With Pembrolizumab for Patients With Locally Advanced or Metastatic Urothelial Cancer

The US Food and Drug Administration (FDA) has approved enfortumab vedotin-ejfv with pembrolizumab for treating patients with locally advanced or metastatic urothelial cancer (la/mUC). The combination treatment was approved on December 15, 2023, based on results from the open-label, randomized EV-302/KEYNOTE-A39 trial.

The trial consisted of 886 patients with la/mUC who had not received prior systemic therapy for advanced disease. The participants were randomized at a 1:1 ratio—stratified by cisplatin eligibility, programmed death-ligand 1 expression, and presence of liver metastases—with patients receiving either enfortumab vedotin-ejfv with pembrolizumab or platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). The main outcome measures were overall survival (OS) and progression-free survival (PFS).

Overall, the study found that there were significant improvements in both OS and PFS for the patients treated with enfortumab vedotin-ejfv plus pembrolizumab vs those who received platinum-based chemotherapy.

Key results from the trial include:

• For patients who received enfortumab vedotin-ejfv with pembrolizumab the median OS was 31.5 months (95% CI: 25.4, not estimable) vs 16.1 months (95% CI: 13.9, 18.3) for those who received platinum-based chemotherapy (hazard ratio [HR] 0.47 [95% CI: 0.38, 0.58]; P < .0001).
• For patients who received enfortumab vedotin-ejfv with pembrolizumab the median PFS was 12.5 months (95% CI: 10.4, 16.6) vs 6.3 months (95% CI: 6.2, 6.5) for those who received platinum-based chemotherapy (HR 0.45 [95% CI: 0.38, 0.54]; P < .0001).

The most common adverse reactions occurred in ≥20% of patients who received the combination treatment and included laboratory abnormalities such as increased aspartate aminotransferase, increased creatinine, rash, increased glucose, diarrhea, alopecia, decreased weight, decreased appetite, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection, and decreased platelets.

The recommended dose for enfortumab vedotin-ejfv when given with pembrolizumab is 1.25 mg/kg (at a maximum of 125mg for patients ≥ 100 kg). It should be administered as an intravenous infusion over 30 minutes on the first and eighth day over a period of 21 days until disease progression or unacceptable toxicity occurs. Patients should receive 200 mg of pembrolizumab when given with enfortumab vedotin-ejfv, and it should be administered as an intravenous infusion every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or two years of therapy.

The approval was granted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. The Real-Time Oncology Review pilot program was used for this review to streamline the data submission before the entire clinical application was submitted.

FDA. FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. December 15, 2023. Accessed January 9, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer