Astellas Pharma and Seagen announced completion of submissions for two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for PADCEV® (enfortumab vedotin-ejfv). One submission, based on the phase 3 EV-301 trial, seeks to convert PADCEV's accelerated approval to regular approval. The second submission, based on the pivotal trial EV-201's second cohort, requests an expansion of the current label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin.
The FDA is reviewing both applications under the Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.
"The FDA's review of our applications under Real-Time Oncology Review supports our efforts to expand PADCEV's availability as a treatment option for more patients as quickly as possible," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "Locally advanced or metastatic urothelial cancer is an aggressive disease with limited treatment options."
The sBLA for regular approval of PADCEV in the U.S. is supported by data from the global EV-301 phase 3 confirmatory trial, which compared PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The trial's primary endpoint was overall survival of patients treated with PADCEV vs. chemotherapy, and full results were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in the New England Journal of Medicine.
The second submission, for a label expansion in the U.S., is based on results from the second cohort of EV-201, a pivotal phase 2 clinical trial evaluating PADCEV in patients with locally advanced or metastatic urothelial cancer who had received prior immunotherapy treatment but were not eligible for cisplatin. The trial's primary endpoint was objective response rate, and full results were presented at ASCO GU.
"Advanced bladder cancer patients urgently need more treatment options," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Based on recently presented clinical trial results, PADCEV could address a significant unmet need for more patients with advanced urothelial cancer after initial immunotherapy treatment."
In 2019 PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.
The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.
The EV-201 trial is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally. The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, pro...
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