FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma
Regulatory approval: On April 3, 2023, the FDA granted accelerated approval to enfortumab vedotin-ejfv plus pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. The decision was supported by EV-103/KEYNOTE-869 (NCT03288545), where 121 patients received the combination. Confirmed ORR was 68% (12% complete responses) by blinded independent central review using RECIST v1.1; median duration of response was 22 months in dose escalation+Cohort A and not reached in Cohort K.
FDA accelerated approval (Apr 3, 2023)
The US FDA granted accelerated approval to enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for locally advanced or metastatic urothelial carcinoma in patients ineligible for cisplatin-containing chemotherapy.
Evidence basis
Efficacy was evaluated in EV-103/KEYNOTE-869 (NCT03288545), a multi-cohort study (dose escalation cohort, Cohort A, Cohort K). Dose escalation and Cohort A were single-arm combination cohorts; Cohort K randomized patients to the combination vs enfortumab vedotin alone. Eligible patients had no prior systemic therapy for locally advanced/metastatic disease and were cisplatin-ineligible. 121 patients received the combination.
Primary efficacy measures: objective response rate (ORR) and duration of response (DoR) assessed by blinded independent central review per RECIST v1.1.
Results (combination; n=121): confirmed ORR 68% (95% CI, 59–76), including 12% complete responses. Median DoR was 22 months (range, 1+ to 46+) for dose escalation+Cohort A; for Cohort K, median DoR was not reached (range, 1 to 24+).
Safety and dosing (per FDA communication)
Common adverse reactions (>20%; including lab abnormalities) included increased glucose, rash, peripheral neuropathy, fatigue, and others.
Recommended combination dosing: enfortumab vedotin-ejfv 1.25 mg/kg (max 125 mg if ≥100 kg) IV Days 1 and 8 of a 21-day cycle; pembrolizumab 200 mg q3w or 400 mg q6w (given after enfortumab vedotin on the same day), up to 24 months.
The application received priority review and breakthrough designation.