Astellas Pharma Inc.

02/12/2020 | Press release | Distributed by Public on 02/11/2020 18:22

Seattle Genetics and Astellas Announce Updated Results from Phase 1b/2 Trial of PADCEV™ (enfortumab vedotin-ejfv) in Combination with Immune Therapy Pembrolizumab as[...]

- After Median Follow-Up of 11.5 Months, 73 Percent of Patients Had Confirmed Tumor Response with Majority of Responses Still Ongoing; No New Safety Signals Observed for the Combination -

- Findings To Be Presented During an Oral Session at the 2020 Genitourinary Cancers Symposium -

BOTHELL, Wash. and TOKYO, February 10, 2020 - Seattle Genetics, Inc. (Nasdaq:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., 'Astellas') today announced updated results from the phase 1b/2 clinical trial EV-103 in previously untreated patients with locally advanced or metastatic urothelial cancer who were ineligible for treatment with cisplatin-based chemotherapy. Forty-five patients were treated with the combination of PADCEV™ (enfortumab vedotin-ejfv) and pembrolizumab and were evaluated for safety and efficacy. After a median follow-up of 11.5 months, the study results continue to meet outcome measures for safety and demonstrate encouraging clinical activity for this platinum-free combination in a first-line setting. Updated results will be presented during an oral session on Friday, February 14 at the 2020 Genitourinary Cancers Symposium in San Francisco (Abstract #441). Initial results from the study were presented at the European Society of Medical Oncology Congress in September 2019.

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.1,2

'Cisplatin-based chemotherapy is the standard treatment for first-line advanced urothelial cancer; however, it isn't an option for many patients,' said Jonathan E. Rosenberg, M.D., Medical Oncologist and Chief, Genitourinary Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York. 'I'm encouraged by these interim results, including a median progression-free survival of a year for patients who received the platinum-free combination of PADCEV and pembrolizumab in the first-line setting.'

In the study, 58 percent (26/45) of patients had a treatment-related adverse event greater than or equal to Grade 3: increase in lipase (18 percent; 8/45), rash (13 percent; 6/45), hyperglycemia (13 percent; 6/45) and peripheral neuropathy (4 percent; 2/45); these rates were similar to those observed with PADCEV monotherapy.3 Eighteen percent (8/45) 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 (arthralgia, dermatitis bullous, pneumonitis, lipase increased, rash erythematous, rash maculo-papular, tubulointerstitial nephritis, myasthenia gravis). None of the adverse events of clinical interest were Grade 5 events. Six patients (13 percent) discontinued treatment due to treatment-related adverse events, most commonly peripheral sensory neuropathy. As previously reported, there was one death deemed to be treatment-related by the investigator attributed to multiple organ dysfunction syndrome.

The data demonstrated the combination of PADCEV plus pembrolizumab shrank tumors in the majority of patients, resulting in a confirmed objective response rate (ORR) of 73.3 percent (33/45; 95% Confidence Interval (CI): 58.1, 85.4) after a median follow-up of 11.5 months (range, 0.7 to 19.2). Responses included 15.6 percent (7/45) of patients who had a complete response (CR) and 57.8 percent (26/45) of patients who had a partial response. Median duration of response has not yet been reached (range 1.2 to 12.9+ months). Eighteen (55%) of 33 responses were ongoing at the time of analysis, with 83.9% of responses lasting at least 6 months and 53.7% of responses lasting at least 12 months (Kaplan-Meier estimate). The median progression-free survival was 12.3 months (95% CI: 7.98, -) and the 12-month overall survival (OS) rate was 81.6 percent (95% CI: 62 to 91.8 percent); median OS has not been reached.

'These updated data are encouraging and provide support for the recently initiated phase 3 trial EV-302 that includes an arm evaluating PADCEV in this platinum-free combination in the first-line setting,' said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.

'These additional results support continued evaluation of PADCEV in combination with other agents and at earlier stages of treatment for patients with urothelial cancer,' said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.

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