FDA Grants Regular Approval, Expands Indication for Enfortumab Vedotin-ejfv for Patients With Locally Advanced or Metastatic Urothelial Cancer

The FDA has granted enfortumab vedotin-ejfv (Padcev; Astellas Pharma and Seagen) both a regular approval and a new indication expansion for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received 1 or more prior lines of therapy. Patients who are cisplatin-ineligible often have limited treatment options available with a poor prognosis.

Because of these limitations around available treatments, the FDA granted an accelerated approval for enfortumab vedotin-ejfv in 2019 to treat adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before or after surgery, or in a locally advanced or metastatic urothelial cancer setting.

The FDA converted their approval from an accelerated approval to a regular approval based on 2 supplemental biologics license applications (sBLAs) assessed within the real-time oncology review pilot program. Additionally, the FDA based their label expansion on the data provided in these 2 sBLAs.

"The FDA's decision to convert accelerated approval to regular approval was based on data from the phase 3 EV-301 trial, which had a primary endpoint of overall survival for patients treated with Padcev versus chemotherapy," said Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head, Astellas, in a press release. "With Padcev, for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy."

During the phase 3 trial, the investigators compared enfortumab vedotin-ejfv to chemotherapy in adult patients (n=608) with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. When observing the data at the pre-specified interim analysis point, patients who received enfortumab vedotin-ejfv (n=301) had a median increased survival of 3.9 months in comparison to those who received chemotherapy (n=307).

For the first cohort of patients in the EV-301 trial, the median overall survival was found to be 12.9 months among those who received enfortumab vedotin-ejfv compared to 9.0 months for those who received chemotherapy [hazard ratio=0.70 (95% confidence interval: 0.56, 0.89), p=0.001].

During the EV-301 trial, the investigators observed that the most common all-grade adverse events (AEs) occurred at a rate of ≥20% and included rash, fatigue, peripheral neuropathy, alopecia, decreased appetite, diarrhea, pruritus, nausea, constipation, dysgeusia, musculoskeletal pain, dry eye, pyrexia, abdominal pain, and anemia.

"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," said Roger Dansey, MD, chief medical officer, Seagen, in the press 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."

The second cohort of the EV-201 trial included patients who had not received a platinum-containing chemotherapy and were ineligible for cisplatin. Among this cohort, 51% of those who received enfortumab vedotin-ejfv had an objective response [95% CI: 39.8, 61.3] per blinded independent central review after a median follow-up of 16 months, with a median duration of response of 13.8 months [95% CI: 6.4, not reached].

Additionally, the investigators observed that the most common all-grade AEs occurred at a rate of ≥20% and included rash, peripheral neuropathy, alopecia, fatigue, decreased appetite, anemia, diarrhea, pruritus, weight decreased, nausea, dry eye, and dysgeusia.

"Almost half of advanced bladder cancer patients 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," said the lead investigator Evan Y. Yu, MD, Division of Oncology, Department of Medicine, University of Washington School of Medicine, in the press release. "A new regulatory approval for enfortumab vedotin is an important clinical advance and can help serve this unmet need."

REFERENCE

U.S. FDA Grants Regular Approval and Expands Indication for PADCEV® (enfortumab vedotin-ejfv) for Patients with Locally Advanced or Metastatic Urothelial Cancer. Bothell, WA: Astellas Pharma and Seagen; July 9, 2021. [email] Accessed July 14, 2021.