Phase 1b Trial of Enfortumab Vedotin in Combination with Immune Checkpoint Inhibitor Therapies in Locally Advanced or Metastatic Urothelial Cancer

Truckee, CA ( Seattle Genetics, Inc. and Astellas Pharma Inc. announced dosing of the first patient in EV-103, a phase 1b clinical trial evaluating the safety and tolerability of enfortumab vedotin in combination with pembrolizumab or atezolizumab, two types of immune checkpoint inhibitor (CPI) therapies, for first- or second-line treatment of patients with locally advanced or metastatic urothelial cancer. Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) designed to deliver the cell-killing agent monomethyl auristatin E (MMAE) to the target Nectin-4.
“The initiation of EV-103 is an important step in investigating the utility of enfortumab vedotin in earlier lines of therapy, including the first-line setting, for locally advanced and metastatic urothelial cancer, where patients ineligible for cisplatin-based chemotherapy continue to have limited treatment options,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “This study represents Seattle Genetics’ third ADC under clinical evaluation in combination with CPIs, highlighting our vision that ADCs could be the preferred partners for immuno-oncology agents for patients with solid tumors and hematological cancers.”
The EV-103 study is a single arm, open label multicenter trial that will enroll up to 85 patients with locally advanced or metastatic urothelial cancer who are ineligible for first line cisplatin-based chemotherapy or have progressed following treatment with a regimen containing platinum-based chemotherapy. Enfortumab vedotin will be administered during weeks one and two of every three-week cycle, and pembrolizumab or atezolizumab will also be administered during week one of this period. The primary objective of the trial is to assess the safety and tolerability of enfortumab vedotin in combination with CPI therapy. Secondary endpoints include the recommended dose in combination with CPIs, overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS), among other measures.

“We are pleased to be moving forward with evaluating enfortumab vedotin in combination with CPI therapy, as we look to further investigate the potential of this agent in some of the hardest-to-treat cancers,” said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. “Many patients do not respond to or relapse after treatment with CPIs, and we are committed to exploring additional ways to potentially address the unmet needs of the urothelial cancer community.”

Enfortumab vedotin is also being studied as monotherapy in a pivotal clinical trial for patients with advanced urothelial cancer who have received prior CPI therapy, called EV-201 (NCT03219333), to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations.

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ASCO 2017: Astellas and Seattle Genetics Announce Updated Enfortumab Vedotin Phase 1 Data in Metastatic Urothelial Cancer
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