FDA approves enfortumab vedotin for locally advanced, metastatic urothelial carcinoma
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The FDA today granted approval to enfortumab vedotin-ejfv for treatment of adults with locally advanced or metastatic urothelial cancer.
The approval applies to patients previously treated with a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy, for whom the agent received accelerated approval in 2019, as well as those who are not eligible for cisplatin-containing chemotherapy and who previously received at least one prior line of therapy.
Enfortumab vedotin-ejfv (Padcev; Astellas, Seagen) is a first-in-class antibody-drug conjugate directed against nectin-4, a protein highly expressed in urothelial cancers.
The FDA based the conversion to regular approval and the label expansion on a pair of supplemental biologics license applications reviewed under the agency’s Real-Time Oncology Review program, according to a company-issued press release.
“Padcev is the first and only FDA-approved therapy for patients with locally advanced or metastatic urothelial cancer who have received immunotherapy and cannot receive cisplatin,” Roger Dansey, MD, chief medical officer for Seagen, said in the release. “Because of the FDA’s Real-Time Oncology Review, we’re able to make Padcev available as early as possible to these patients, who have limited treatment options due to their age or comorbid conditions.”
Researchers conducted the open-label, randomized phase 3 EV-301 trial as required to confirm the clinical benefit of the accelerated approval. The trial compared enfortumab vedotin with chemotherapy among 608 adults with locally advanced or metastatic urothelial cancer who had received a PD-1 or PD-L1 inhibitor in addition to platinum-based chemotherapy.
Patients received either 1.25 mg/kg enfortumab vedotin on days 1, 8 and 15 of each 28-day cycle (n = 301) or investigator’s choice of docetaxel, paclitaxel or vinflunine (n = 307).
OS served as the primary endpoint. Secondary endpoints included investigator-assessed PFS, safety, objective response rate and disease control rate per RECIST version 1.1.
As Healio previously reported, results presented at this year’s Genitourinary Cancers Symposium showed the enfortumab vedotin group demonstrated significantly longer median OS (12.9 months vs. 9 months; HR = 0.7; 95% CI, 0.56-0.89) and median PFS (5.6 months vs. 3.7 months; HR = 0.62; 95% CI, 0.51-0.75), as well as a higher ORR (40.6% vs. 17.9%; P < .0001).
The agent’s efficacy among patients ineligible for cisplatin was evaluated in cohort 2 of the single-arm, phase 2 EV-201 trial, which included 89 adults with locally advanced or metastatic disease who had been treated with a PD-1 or PD-L1 inhibitor. Confirmed ORR by blinded independent central review served as the primary endpoint.
Median follow-up was 16 months.
Results showed a confirmed ORR of 51% (95% CI, 39.8-61.3) and a median response duration of 13.8 months (95% CI, 6.4-not reached).
Common adverse events that occurred among at least 20% of patients included rash, fatigue, peripheral neuropathy, alopecia, decreased appetite, pruritus, nausea, dry eye and dysgeusia.
“Almost half of [patients with advanced bladder cancer] cannot receive cisplatin-based chemotherapy. Many of these patients will receive first-line immunotherapy. If their cancer does not respond or if it progresses after prior response to immunotherapy, there is an urgent need for more treatment options as there is currently no standard of care,” Evan Y. Yu, MD, of the division of oncology in the department of medicine at University of Washington School of Medicine and EV-201 trial lead investigator, said in the company-issued press release. “A new regulatory approval for enfortumab vedotin is an important clinical advance and can help serve this unmet need.”
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