Seattle Genetics, Astellas Phase 1 Trial of Investigational Agent Enfortumab Vedotin plus Pembrolizumab met outcomes: 71% patients confirm response.

Seattle Genetics, and Astellas Pharma’s study met outcomes for safety and 71 Percent of patients with locally advanced or metastatic urothelial (bladder) cancer had a confirmed response, the companies presented Saturday at ESMO Congress in Barcelona.

TOKYO & BOTHELL, Wash.–(BUSINESS WIRE)–Seattle Genetics, Inc. (Nasdaq:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced initial results from the phase 1 clinical trial EV-103. Forty-five 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. The data will be presented during an oral session today at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain (Abstract #901O).

Enfortumab vedotin is a first-in-class antibody drug conjugate (ADC) that targets Nectin-4, a protein present on almost all urothelial tumor cells and associated with cancer formation.¹

“Advanced urothelial cancer is an aggressive disease for which more options are needed, especially for patients who are ineligible for first-line treatment with cisplatin,” said Dr. Christopher J. Hoimes, Director, Genitourinary Oncology, Case Comprehensive Cancer Center at University Hospitals Seidman Cancer Center, Cleveland, Ohio. “This study tests the combination of the investigational agent enfortumab vedotin with the PD-1 inhibitor pembrolizumab, in a biomarker unselected population. Initial results provide support for further development of enfortumab vedotin combinations in this and other settings of urothelial cancer.”

Fifty-one percent of patients (23/45) had an adverse event greater than or equal to Grade 3. Among these events, an increase in lipase was the most frequent (13 percent; 6/45). Four patients (9 percent) 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.

Treatment-related adverse events of clinical interest that were greater than or equal to Grade 3 were rash (11 percent; 5/45), hyperglycemia (7 percent; 3/45) and peripheral neuropathy (4 percent; 2/45); these rates were similar to those observed with enfortumab vedotin monotherapy.² Eleven percent (5/45) 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 (one event each of pneumonitis, dermatitis bullous, hyperglycemia, tubulointerstitial nephritis, myasthenia gravis). 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 (ORR) of 71 percent (32/45; 95% Confidence Interval (CI): 55.7, 83.6). The complete response (CR) rate was 13 percent (6/45). Fifty-eight percent (26/45) of patients had a partial response and 22 percent (10/45) had stable disease. Ninety-one percent of responses were observed at the first assessment.

“These data are encouraging and support further exploration of a potential platinum-free combination of pembrolizumab and the investigational agent enfortumab vedotin,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.

“We are motivated by these results, and we will continue to study enfortumab vedotin alone and in combination with other agents in different stages of urothelial cancer,” said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.

Enfortumab vedotin is currently under review by the U.S. Food and Drug Administration (FDA) 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.