medwireNews: Preliminary results from a pivotal trial of enfortumab vedotin, an antibody–drug conjugate targeting Nectin-4, show a “clinically meaningful” response in patients with unresectable locally advanced or metastatic urothelial cancer.
Daniel Petrylak (Yale School of Medicine, New Haven, Connecticut, USA) told delegates at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA, that enfortumab vedotin is the “[f]irst novel therapeutic to demonstrate substantial clinical activity in patients who progressed after platinum chemotherapy and a PD-1/L1 inhibitor.”
The phase II EV-201 trial enrolled 125 patients (median age 69 years, 70% men) with unresectable locally advanced or metastatic urothelial cancer who had previously been treated with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy (median three prior systemic therapies).
All patients in the open-label, multicenter study received intravenous enfortumab vedotin 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle.
After a median treatment duration of 4.6 months (maximum 15.6 months with 20 patients still on-treatment), the RECIST objective response rate (ORR) was 44%, with 12% of patients experiencing a complete response.
The median time to response was 1.8 months, and the median response duration was 7.6 months with 44% of responders still being followed-up.
Petrylak reported that responses were observed across all subgroups, including patients who did not respond to PD-1 or PD-L1 inhibition (ORR=41%), and those with liver metastases (ORR=38%).
At the time of the analysis, median progression-free survival was 5.8 months while median overall survival was 11.7 months.
The treatment was “well tolerated with a manageable safety profile,” according to Petrylak, who noted that few (12%) patients discontinued treatment due to adverse events (AEs).
The most common AE of any grade was fatigue (50%), followed by alopecia (49%), decreased appetite (44%), peripheral sensory neuropathy (40%), and dysgeusia (40%).
Among the treatment-related AEs of interest, any peripheral neuropathy occurred in half of patients overall and in 3% at grade 3 or higher, while rash was reported by 48% and 12%, respectively.
There was one treatment-related death, which was attributed to interstitial lung disease, but Petrylak noted that this was confounded by high-dose corticosteroid use and suspected Pneumocystis jiroveci infection.
He concluded that the data “support submission to the FDA for accelerated approval,” adding that “[i]f approved, enfortumab vedotin may have the potential to become a new standard of care in patients [with urothelial cancer] who have progressed after platinum and PD-1/L1 inhibitors.”
Petrylak also said that enrollment of a second cohort of patients who had previously received a PD-1/PD-L1 inhibitor but were platinum naïve and cisplatin ineligible is ongoing.
By Laura Cowen
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2019 ASCO Annual Meeting; Chicago, Illinois, USA: 31 May–4 June