FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer

FDA approval: enfortumab vedotin-ejfv + pembrolizumab in la/mUC (Dec 15, 2023)

Type: Regulatory approval (FDA)

On December 15, 2023, the FDA approved enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial cancer (la/mUC). The FDA previously granted accelerated approval to this combination for patients with la/mUC ineligible for cisplatin-containing chemotherapy.

Supporting evidence

Approval was supported by EV-302/KN-A39 (NCT04223856), an open-label, randomized trial enrolling 886 patients with la/mUC and no prior systemic therapy for advanced disease. Patients were randomized 1:1 to enfortumab vedotin-ejfv + pembrolizumab or platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin). Stratification factors included cisplatin eligibility, PD-L1 expression, and liver metastases.

Primary outcomes: overall survival (OS) and progression-free survival (PFS) by blinded independent central review.

Results showed statistically significant improvements:

• OS: 31.5 vs 16.1 months (HR 0.47; 95% CI 0.38–0.58; p<0.0001)
• PFS: 12.5 vs 6.3 months (HR 0.45; 95% CI 0.38–0.54; p<0.0001)

Safety and dosing highlights

Common (≥20%) adverse reactions/lab abnormalities included AST/ALT increases, creatinine increase, rash, hyperglycemia, peripheral neuropathy, lipase increase, cytopenias, fatigue, diarrhea, alopecia, and others.

Recommended dosing when combined: enfortumab vedotin-ejfv 1.25 mg/kg IV on Days 1 and 8 of a 21-day cycle; pembrolizumab 200 mg IV q3w or 400 mg q6w.

The review used Project Orbis and the FDA’s Real-Time Oncology Review pilot.