Dr. Singh on the Continued Investigation of Enfortumab Vedotin/Pembrolizumab in Urothelial Cancer

Vikas Kumar Singh, MD, medical oncologist, Baptist Health, discusses the potential benefit of the combination of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for the treatment of patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy.

In December 2022, the FDA granted a priority review to supplemental biologics license applications for enfortumab vedotin and pembrolizumab for treatment as combiantion therapy in this patient population, based on the outcomes from the A, K, and dose-escalation cohorts evaluated in the phase 1b/2 KEYNOTE-869/EV-103 trial (NCT03288545).

The phase 1b/2 trial evaluated the combination therapy with a primary end point of confirmed overall response rate (ORR) by blinded independent central review, with secondary end points that included duration of response, overall survival (OS), and safety. Results from

dose escalation/cohort A demonstrated an ORR of 73.3%, and findings from cohort K presented at the 2022 ESMO Congress showed an ORR of 64.5% with a manageable safety profile.

Investigators are also evaluating enfortumab vedotin plus pembrolizumab in the ongoing phase 3 trial (NCT04223856), which is examining the combination vs chemotherapy alone in patients with previously untreated advanced urothelial cancer. The trial is enrolling patients who are both cisplatin eligible and cisplatin ineligible, Singh notes.

Currently, the standard of care for patients with previously untreated advanced urothelial cancer is chemotherapy followed by maintenance immunotherapy, Singh continues. However, the regimen consisting of enfortumab vedotin plus pembrolizumab could represent a non-chemotherapy option for this patient population, Singh says. If enfortumab vedotin plus pembrolizumab demonstrates a survival improvement vs chemotherapy for patients in the frontline setting, this regimen may be practice changing, Singh concludes.