Enfortumab Vedotin Combo Gets Accelerated FDA Nod for Urothelial Cancer

The FDA has granted approval to enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) as a combination therapy for patients with locally advanced or metastatic urothelial cancer who cannot receive cisplatin-based chemotherapy, according to a press release from FDA.¹

"It was groundbreaking to use both [enfortumab vedotin and pembrolizumab] in the clinical trial setting," according to an expert from UCLA Health.

The approval was based on results from cohorts A and K of the phase 1b/2 EV-103 or KEYNOTE-869 trial (NCT03288545). A total of 121 patients received the combination. The objective response rate (ORR) was 68% (95% CI, 59%-76%) for patients receiving the regimen, which included a complete response rate of 12.0%.

In the dose escalation cohort and cohort A, the median duration of response (DOR) was 22 months (range, 1+ to 46+), and was not reached in Cohort K (range, 1-24+).

Based on topline data, common adverse effects (AEs) occurring in more than 20% of patients included increased glucose, rash, decreased hemoglobin, increased creatinine, peripheral neuropathy, and fatigue.

“We had enfortumab [monotherapy] for urothelial cancer, metastatic and nonmetastatic for a while. Then we also had pembrolizumab [Keytruda] by itself, for the treatment of urothelial cancer. Most of these drugs, indeed showed that it improved the progression-free survival and overall survival in this population of patients. It was groundbreaking to use both drugs in the clinical trial setting,” Nazy Zomorodian, NP, director of the Genitourinary Clinical Trials Unit and assistant professor and Nurse Practitioner for the Department of Urology at UCLA Health, said in an interview with CancerNetwork^®.

Results from cohort K were previously presented at the 2022 European Society for Medical Oncology (ESMO) Congress.²

The primary end point included incidence and severity of adverse effects, laboratory abnormalities, objective response rate (ORR), and pathological complete response. Secondary end points included incidence of dose-limiting toxicity, confirmed ORR, disease control rate, and duration of response (DOR).

The confirmed ORR by investigator assessment was 64.5% (95% CI, 52.7%-75.1%) with a complete response rate of 10.5% in the combination arm vs 4.1% in the enfortumab vedotin monotherapy arm. The median DOR was not reached in the combination arm but was 13.2 months in the monotherapy arm.

In July 2021, the FDA previously approved enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1 or PD-L1 inhibitor.³

References

1. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. News release. FDA. April 3, 2023. Accessed April 3, 2023. http://bit.ly/3nGtsjh
2. Rosenberg JE, Milowsky M, Ramaurthy C, et al. Study EV-103 cohort K: antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC). Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089
3. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. News release. FDA. July 9, 2021. Accessed December 20, 2022. https://bit.ly/3hsvrln