FDA D.I.S.C.O. Burst Edition: FDA approval of Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) for locally advanced or metastatic urothelial carcinoma

Regulatory approval: On April 3, 2023, the FDA granted accelerated approval to enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) 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 (multi-cohort; some single-arm, Cohort K randomized). In 121 treated patients, confirmed ORR was 68% (12% CR); median DOR was 22 months in dose-escalation+Cohort A and not reached in Cohort K.

FDA accelerated approval (April 3, 2023)

The US FDA granted accelerated approval to enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy.

Key evidence

Efficacy was evaluated in EV-103/KEYNOTE-869, a multi-cohort study (dose escalation cohort, Cohort A, Cohort K). The dose escalation cohort and Cohort A were single-arm cohorts of enfortumab vedotin-ejfv plus pembrolizumab; Cohort K randomized patients to the combination or enfortumab vedotin-ejfv alone. Eligible patients had no prior systemic therapy for locally advanced/metastatic disease and were cisplatin-ineligible. 121 patients received the combination.

Major efficacy endpoints were objective response rate (ORR) and duration of response (DOR) by blinded independent central review using RECIST v1.1.

  • Confirmed ORR: 68% (12% complete responses)
  • Median DOR: 22 months (dose escalation + Cohort A); not reached (Cohort K)

Safety

Common adverse reactions (>20%), including lab abnormalities, included increased glucose, increased AST, rash, decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased lymphocytes, fatigue, increased ALT, and others as reported by FDA.

The FDA noted use of an Assessment Aid voluntary submission to facilitate review.

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