Updated Results From the EV-103 Trial Will Be Presented at the ASCO GU 2020

San Francisco, CA (UroToday.com) --  Seattle Genetics, Inc. and Astellas Pharma Inc. 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.

- 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
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 six 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. 
About the EV-103 Trial
EV-103 is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating the safety, tolerability, and efficacy in muscle-invasive, locally advanced and first- and second-line metastatic urothelial cancer.
The dose-escalation cohort and expansion cohort A include locally advanced or metastatic urothelial cancer patients who are ineligible for cisplatin-based chemotherapy. Patients were dosed in a 21-day cycle, receiving an intravenous (IV) infusion of enfortumab vedotin on Days 1 and 8 and pembrolizumab on Day 1. At the time of this initial analysis, 45 patients (five from the dose-escalation cohort and 40 from the dose-expansion cohort A) with locally advanced and/or metastatic urothelial cancer had been treated with enfortumab vedotin (1.25 mg/kg) plus pembrolizumab in the first-line setting.
The primary outcome measure of the cohorts included in this analysis is safety. Key secondary objectives related to efficacy include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). DoR, PFS and OS are not yet mature.
Additional cohorts in the EV-103 study will evaluate enfortumab vedotin:
  • as monotherapy or in combination with pembrolizumab or a platinum chemotherapy in a first-line setting for metastatic disease;
  • in combination with pembrolizumab and carboplatin or cisplatin in first-line metastatic disease;
  • as a monotherapy or in combination with pembrolizumab in muscle-invasive disease;
  • with pembrolizumab in second-line metastatic disease; and
  • with gemcitabine in first- or second-line metastatic disease.3
Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

Citation: "Seattle Genetics And Astellas Announce Updated Results From Phase 1B/2 Trial Of PADCEV™ (Enfortumab Vedotin-Ejfv) In Combination With Immune Therapy Pembrolizumab As Investigational First-Line Treatment For Advanced Bladder Cancer". 2020. Prnewswire.Com.


1. PADCEV [package insert]. Northbrook, IL: Astellas, Inc.
2. Challita-Eid, Pia M., Daulet Satpayev, Peng Yang, Zili An, Karen Morrison, Yuriy Shostak, Arthur Raitano et al. "Enfortumab vedotin antibody–drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models." Cancer research 76, no. 10 (2016): 3003-3013.
3. ClinicalTrials.gov. A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer (EV-103). https://clinicaltrials.gov/ct2/show/NCT03288545.