Enfortumab granted breakthrough therapy designation for metastatic urothelial Ca

March 18, 2020

The FDA has granted Breakthrough Therapy designation for enfortumab vedotin-ejfv (PADCEV) in combination with the anti-PD-1 therapy pembrolizumab (KEYTRUDA) for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

The FDA has granted Breakthrough Therapy designation for enfortumab vedotin-ejfv (PADCEV) in combination with the anti-PD-1 therapy pembrolizumab (KEYTRUDA) for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

The Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the phase Ib/II trial EV-103 (NCT03288545), evaluating patients with locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy treated in the first-line setting with enfortumab vedotin-ejfv in combination with pembrolizumab. Initial results from the trial were presented at the 2019 European Society of Medical Oncology annual congress, and updated findings were presented at the Genitourinary Cancers Symposium in San Francisco.

EV-103 is an ongoing, multi-cohort, open-label, multicenter phase Ib/II trial of enfortumab vedotin-ejfv alone or in combination, evaluating safety, tolerability, and efficacy in muscle-invasive, locally advanced, and first- and second-line metastatic urothelial cancer.

According to Seattle Genetics, Inc. and Astellas Pharma, Inc., data from EV-103 demonstrated the combination of enfortumab vedotin-ejfv plus pembrolizumab shrank tumors in the majority of patients, resulting in a confirmed objective response rate of 73.3% (33/45; 95% Confidence Interval [CI]: 58.1, 85.4) after a median follow-up of 11.5 months (range, 0.7 to 19.2). Responses included 15.6% (7/45) of patients who had a complete response (CR) and 57.8% (26/45) of patients who had a partial response. Median duration of response has not yet been reached (range, 1.2 to 12.9+ months).

Eighteen (55%) of 33 responses were ongoing at the time of analysis, with 83.9% of responses lasting at least 6 months and 53.7% of responses lasting at least 12 months (Kaplan-Meier estimate). The median progression-free survival was 12.3 months (95% CI: 7.98, -) and the 12-month overall survival (OS) rate was 81.6% (95% CI: 62 to 91.8%); median OS has not been reached.

“Cisplatin-based chemotherapy is the standard treatment for first-line advanced urothelial cancer; however, it isn’t an option for many patients. I’m encouraged by these interim results, including a median progression-free survival of a year for patients who received the platinum-free combination of PADCEV and pembrolizumab in the first-line setting,” said EV-103 first author Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York.