Seattle Genetics, Astellas announce results from Phase 1 clinical trial EV-103
Seattle Genetics and Astellas Pharma announced initial results from the phase 1 clinical trial EV-103. 45 patients were evaluated for safety with the combination of the investigational agent enfortumab vedotin and the immune therapy pembrolizumab in previously untreated patients with locally advanced or metastatic urothelial cancer who were ineligible for treatment with cisplatin-based chemotherapy. The study met outcome measures for safety and exhibited encouraging clinical activity for this platinum-free combination in a first-line setting. Enfortumab vedotin is a first-in-class antibody drug conjugate that targets Nectin-4, a protein present on almost all urothelial tumor cells and associated with cancer formation. 51% of patients had an adverse event greater than or equal to Grade 3. Among these events, an increase in lipase was the most frequent. Four patients discontinued treatment due to treatment-related adverse events, most commonly peripheral sensory neuropathy. There was one death deemed to be treatment-related by the investigator attributed to multiple organ dysfunction syndrome. 11% of patients had treatment-related immune-mediated adverse events of clinical interest greater than or equal to Grade 3 that required the use of systemic steroids. None of the adverse events of clinical interest were Grade 5 events. The data demonstrated the combination of enfortumab vedotin plus pembrolizumab shrank tumors in the majority of patients, resulting in a confirmed objective response rate of 71%. The complete response rate was 13%. 58% of patients had a partial response and 22% had stable disease. 91% of responses were observed at the first assessment. Enfortumab vedotin is currently under review by the U.S. Food and Drug Administration for the treatment of patients with locally advanced or metastatic urothelial cancer who have received a PD-1/L1 inhibitor and who have received a platinum-containing chemotherapy in a neoadjuvant/adjuvant, locally advanced or metastatic setting.