Seattle Genetics and Astellas Pharma confirmed the dosing of the first patient in EV-103, a phase Ib clinical trial evaluating the safety and tolerability of enfortumab vedotin in combination with pembrolizumab (Keytruda®; Merck) or atezolizumab (Tecentriq®, Genentech/Roche), two types of immune checkpoint inhibitor (CPI) therapies, for first- or second-line treatment of patients with locally advanced or metastatic urothelial cancer.
Urothelial cancer is most commonly found in the bladder (90%). According to the American Cancer Society, approximately 79,000 people in the U.S. will be diagnosed with bladder cancer during 2017 and almost 17,000 will die from the disease. Outcomes are poor for patients diagnosed with metastatic disease, with a five-year survival rate of five percent.
Enfortumab vedotin is an investigational antibody-drug conjugate or ADC designed to deliver the cell-killing, microtubule-disrupting, agent called monomethyl auristatin E or MMAE to the target Nectin-4, a cell adhesion molecule identified as an ADC target by Astellas, which is expressed on many solid tumors. The drug uses Seattle Genetics’ proprietary linker technology.
“We’re pleased to be moving forward with evaluating enfortumab vedotin in combination with Immune Checkpoint Inhibitor therapy… further investigating the potential … [treatment of patients with] some of the hardest-to-treat cancers…”
“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,” noted 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,” Drachman added.
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,” Benner added
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.
Astellas Pharma, based in Tokyo, Japan and Seattle Genetics (Bothel, Washington) entered into their ADC development collaboration in January 2007 and expanded it in November 2009. Under the collaboration, the companies are co-developing and have options to globally co-commercialize enfortumab vedotin.