Enfortumab Vedotin Shows Positive Topline Results in Pivotal Phase 2 Trial, BLA Filing Planned for This Year

On March 29, Seagen and Astellas jointly announced that their investigational antibody-drug conjugate (ADC) enfortumab vedotin, for the treatment of locally advanced or metastatic urothelial carcinoma, achieved positive top-line results in patients enrolled in Cohort 1 of the pivotal Phase 2 EV-201 trial. Patients in this cohort had previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. Given the significant improvement in objective response rate (ORR) observed in this trial, the two companies plan to submit an application later this year based on the results from Cohort 1 of the EV-201 trial toFDASubmit a Biologics License Application (BLA), while continuing Phase 3 trials to support global expansion.

Urothelial carcinoma is the most common type of bladder cancer, accounting for 90% of all cases. In 2018, globallyDiagnosisThe number of individuals diagnosed with bladder cancer and those who died from it are approximately 549,000 and 200,000, respectively. For patients with advanced urothelial carcinoma, approximately 80% do not respond to PD-1 or PD-L1 inhibitors after failure of platinum-based chemotherapy as the initial treatment. Once urothelial carcinoma metastasizes, the 5-year survival rate for patients is only 4.8%. Currently, there are no approved therapies for patients with urothelial carcinoma whose disease has progressed following treatment with chemotherapy and PD-1 or PD-L1 inhibitors.

Enfortumab vedotin is an antibody-drug conjugate (ADC) comprising two components: a monoclonal antibody targeting Nectin-4, a cell adhesion molecule commonly expressed on the surface of solid tumors, and a microtubule-disrupting agent (MMAE). These two components are linked together using Seagen’s proprietary linker technology. Previously, enfortumab vedotin had receivedFDABreakthrough Therapy Designation Granted.

The EV-201 trial was designed to evaluate the efficacy of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma who had previously received PD-1 or PD-L1 inhibitor therapy, with those who had also received platinum-based chemotherapy assigned to Cohort 1. The primary endpoint of the trial was the objective response rate (ORR) as confirmed by blinded independent central review. The trial results demonstrated an ORR of 44% in patients in Cohort 1. Secondary endpoints included assessments of duration of response, disease control rate, progression-free survival, overall survival, safety, and tolerability. Specific trial data for Cohort 1 will be presented at the upcoming medicalMeetingpublished above.

Dr. Roger Dansey, Chief Medical Officer at Seattle Genetics, stated, “For patients with locally advanced or metastatic urothelial carcinoma, despite the recent approval of multiple checkpoint inhibitors, there remains a significant unmet need for effective therapies among those whose disease continues to progress after both initial chemotherapy and immunotherapy. The current data suggest that enfortumab vedotin may offer benefit to this patient population.”Bio ValleyBioon.com）